Top 10 Pipelines To Watch: 2019 Annual Report

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The return on R&D investment for leading biopharmaceutical manufacturers fell to a nine-year low while the U.S. FDA approved a record-breaking amount of novel medicines during 2018.


Med Ad News’ special report returns with an overview of 10 company pipelines to keep an eye on in 2019 and beyond, including some frequent “Big Pharma” spenders as well as several up-and-coming R&D players making a first-time appearance in this annual compilation.

Top biopharma companies’ return on R&D investment reaches nine-year low

The cost of developing a new medicine has nearly doubled since 2010 while 12 of the top biopharmaceutical companies combined to generate the lowest return on R&D investment in nine years, according to an annual study performed by the Deloitte Centre for Health Solutions. According to the analysis, despite a continuing steady stream of new medicines reaching major markets around the globe, the average return expected to be achieved from the late-stage pipelines of 12 leading biopharma players dropped 1.9 percent during 2018 compared with 3.7 percent in 2017. Overall, the R&D return in 2018 for the large-cap biopharma companies fell by 8.2 percentage points since the 2010 amount of 10.1 percent.

Research shows that returns have been impacted by the growing cost of bringing a medicine to the marketplace. The average cost of bringing a new medicine to market has increased to $2.17 billion, compared to $1.19 billion in 2010, according to Deloitte’s key findings. Forecast peak sales for new drugs decreased from 2017 to $407 million, whereas the 2010 value was $816 million – a decline that reflects a growing concentration on relatively small targeted patient groups, resulting in multiple niche treatments.

“Despite the launch of many successful products, growing development costs and regulatory constraints are making it more difficult than ever for companies to redeem their R&D investment,” noted Colin Terry, a partner in Deloitte’s Life Sciences practice.

Deloitte also analyzed four smaller, more specialized companies. That biopharma cohort was expected to produce an average return rate of 9.3 percent during 2018 versus 12.5 percent in 2017. “This fall was driven by the commercialization of five major drugs in 2018,” the Deloitte analysis explains. “However, these smaller firms continue to outperform their peers, finding success in releasing high-value products. These products have added $70 billion of projected lifetime sales to the commercial portfolio across the four companies. The extension cohort have also increased their forecast peak sales per asset from $952 million in 2013 to $1,165 million in 2018.”

The 12 large-cap biopharma companies analyzed by Deloitte are Pfizer, Roche, Novartis, Sanofi, GlaxoSmithKline, Johnson & Johnson, AstraZeneca, Merck & Co., Eli Lilly, Bristol-Myers Squibb, Takeda and Amgen. The smaller cohort consisted of Biogen, Celgene, Gilead Sciences and AbbVie.

Despite the projected return on R&D investment falling to the lowest level since the study started in 2010, Deloitte analysts say there are opportunities to reverse this trend, which will require new ways of working and a complete digital transformation to unlock R&D productivity and deliver the next generation of scientific breakthroughs. “Companies need to act now and embrace new ways of working, embed new technologies and seek out talent with the right skill sets to maximize their return on investment in pharmaceutical innovation. Our recommendations cover three main focus areas for transformation: technology, collaboration and geography, underpinned by a strong leadership response.”

Record-breaking 59 novel drugs approved by FDA during 2018

The U.S. Food and Drug Administration granted marketing clearance to 59 novel drugs during 2018 – in the form of new molecular entities (NMEs) under New Drug Applications (NDAs) or as new therapeutic biologics under Biologics License Applications (BLAs) – compared to 46 in 2017 and 22 in 2016. In the past decade, the FDA’s Center for Drug Evaluation and Research’s (CDER) averaged about 33 novel medicine approvals per year. These totals do not include drugs approved by FDA’s Center for Biologics Evaluation and Research (CBER), which are separately tracked. CDER’s previous high mark of 53 new product approvals was recorded in 1996.

Among 34 novel approvals in 2018 to help patients with rare or orphan diseases, CDER approved the first medicine to treat patients with a rare inherited form of rickets, a condition that leads to impaired bone growth and development. CDER gave the green light to the first orally administered drug to treat Fabry disease, a rare and serious disorder that can cause many adverse symptoms, including damage to the kidneys and heart. The U.S. regulatory agency cleared for marketing a new drug to treat phenylketonuria (PKU), a rare dietary condition in which patients are born with an inability to break down protein-containing foods and certain sweeteners, and which can lead to brain and nerve damage.

According to CDER, 19 of the 59 novel drugs approved during 2018 represent first-in-class status, which is one indicator of a drug’s potential for strong positive impact on the health of the American people.

A total of 43 out of the 59 novel drug approvals were designated in one or more expedited categories of Fast Track, Breakthrough, Priority Review, and/or Accelerated Approval.

CDER approved 56 of the 59 novel drugs of 2018 (95 percent) on the “first cycle” of review, meaning without a “complete response” letter from the FDA that necessitates re-submission with additional information, resulting in more time before the drug can be cleared for marketing. From 2011 through 2017, CDER approved 250 novel drugs, of which 205 (82 percent) were granted approval during the first cycle.

Big Pharma adopting agile real estate strategies and enhanced entrepreneurial approaches to reinvent R&D

For Big Pharma, finding new blockbuster drugs is becoming increasingly challenging and expensive, according to life sciences experts from professional services firm JLL. Since 2013, smaller enterprises have increased innovation and delivery, bringing a disproportionate amount of new products to the market, JLL analysts say. In 2019, JLL predicts that Big Pharma will adopt agile real estate strategies and enhanced entrepreneurial approaches to reinvent R&D, to compete with smaller companies that have dominated the space.

“Given that a majority of the baseline pharma challenges have been solved, it is the current need for more complex treatments that is driving the need to invest significantly more into R&D,” according to the experts. “As this impact is seen in the length of research, cost of development and lack of deliverable drugs to bring to the market, Big Pharma will be forced to reevaluate their business model, figuring out how they can invest in startups, buy pipelines, bring incubator spaces into the market, create flexible labs space, and much more. As these new industry realities transform how new products are discovered, manufactured and brought to market – it will drive real estate and facilities decisions.”

JLL has identified four trends that are poised to transform the pharma industry during 2019 and beyond:

• Venture capital will continue to floor biopharmaceutical innovators.
• Incubator labs will share the cost burden for drug discovery.
• Flex space will unlock innovation and savings in R&D operations desperate for a facelift.
• High-risk, high-reward mid-tier pharmaceutical companies will focus on flexibility and non-core services.

“Without productive, efficient R&D processes that deliver strong revenues to drive reinvestment into continuing innovation, the business model falls apart,” says Roger Humphrey, executive managing director and leader of JLL’s Life Sciences group. “In 2019, Big Pharma will focus on solving the R&D conundrum through investing in startups, buying pipelines, bringing incubator spaces into the market, creating flexible lab spaces, embarking on joint ventures and more.”

For more details about the four pharma trends to watch in 2019 and beyond with analysis from Roger Humphrey, please visit:


Top 10 Pipelines To Watch

Bluebird Bio
Bristol-Myers Squibb/Celgene



The second-best drug pipeline in the industry is expected to drive 10 percent long-term EPS growth and deliver about 18-23 percent long-term total returns from today’s price,” wrote Seeking Alpha analysts on Jan. 28, 2019. “AbbVie’s medium-term future growth hinges on five key drugs: 

• Blood cancer drug Imbruvica, estimated $9.6 billion in 2024 annual sales (17 percent CAGR growth between 2017 and 2024)
• Endometriosis drug Orilissa, $1 billion in annual peak sales (recently launched)
• Cancer drug Venclexta, $3 billion in annual peak sales
• Immunology drugs risankizumab and upadacitinib, $10-12 billion in combined peak annual sales”

The first-in-class, oral, once-daily therapy Imbruvica (ibrutinib) is FDA-approved in six distinct diseases: chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenström’s macroglobulinemia, along with previously treated mantle cell lymphoma, previously treated marginal zone lymphoma, and previously treated chronic graft-versus-host disease. Imbruvica is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. According to AbbVie, the blockbuster medicine has a robust clinical oncology development program, with more than 130 ongoing clinical studies. As of late January, there were 30 ongoing company-sponsored trials – 14 of which were in Phase III – and more than 100 investigator-sponsored trials and external collaborations that were active globally. More than 135,000 patients worldwide have been treated with the Bruton’s tyrosine kinase (BTK) inhibitor in clinical practice and studies.

Orilissa (elagolix) became the first FDA-approved oral treatment for the management of moderate-to-severe pain associated with endometriosis in more than a decade after receiving U.S. regulatory clearance in July 2018. Orilissa is the first oral gonadotropin-releasing hormone (GnRH) antagonist specifically developed for women with moderate-to-severe endometriosis pain. The orally administered, nonpeptide small-molecule GnRH receptor antagonist is being investigated in diseases that are mediated by ovarian sex hormones, including uterine fibroids and endometriosis. As of November 2018, elagolix had been studied in more than 40 clinical trials, totaling over 3,700 subjects. U.S. regulatory submission for elagolix for uterine fibroids is anticipated during mid-2019.

The first-in-class drug Venclexta/Venclyxto (venetoclax) is approved for marketing in more than 50 countries. With another approved indication in November 2018, Venclexta is marketed in the United States for use in two different blood cancers: newly diagnosed acute myeloid leukemia (AML) and relapsed/refractory chronic lymphocytic leukemia (CLL). The oral B-cell lymphoma-2 (BCL-2) inhibitor is being studied in two ongoing Phase III studies in the AML patient population ineligible for intensive chemotherapy. In addition to CLL, venetoclax is being investigated in several other hematologic malignancies: multiple myeloma (MM), non-Hodgkin lymphoma (NHL) and myelodysplastic syndrome (MDS). The product is being developed by AbbVie and Roche and is jointly commercialized by AbbVie and Genentech – a member of the Roche Group – in the United States and by AbbVie outside of the U.S.

While Imbruvica, Orilissa and Venclexta are generating sales growth for AbbVie, the company also is excited about two best-in-category agents: the pipeline assets upadacitinib and risankizumab. According to AbbVie, the two new drug candidates have the potential to be approved for 12+ indications and contribute more than $10 billion in incremental risk-adjusted sales by 2025.

Risankizumab is considered one of the five drugs to watch in 2019 among new and potentially expensive treatments coming to market according to Optum, a leading information and technology-enabled health services business. AbbVie management is anticipating the expected approval of risankizumab during first-half 2019. The investigational interleukin-23 (IL-23) inhibitor is being jointly developed in collaboration with Boehringer Ingelheim, with AbbVie leading future development and commercialization of risankizumab worldwide. Phase III studies in psoriasis and Crohn’s disease continue. The new drug candidate is additionally being evaluated in clinical trials for the treatment of psoriatic arthritis (Phase II) and ulcerative colitis (Phase IIb/III).

IL-23 is a key cytokine involved in the inflammatory processes. The cytokine is believed to be linked to various chronic immune-mediated diseases.

Discovered and developed by AbbVie, the oral, small molecule JAK1-selective inhibitor upadacitinib is being studied for a variety of immune-mediated diseases. In addition to Phase III studies in rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, ulcerative colitis and atopic dermatitis, the investigational compound is being evaluated for treating ankylosing spondylitis.

A New Drug Application (NDA) to the U.S. Food and Drug Administration and a Marketing Authorization Application (MAA) to the European Medicines Agency was submitted in December 2018 for upadacitinib for treating adults with moderate-to-severe rheumatoid arthritis. The NDA and MAA are supported by clinical data from the global upadacitinib SELECT Phase III rheumatoid arthritis program studying more than 4,000 patients with moderate-to-severe rheumatoid arthritis across five Phase III trials. In all studies, upadacitinib met all primary and ranked secondary endpoints. According to AbbVie, the robust SELECT Phase III rheumatoid arthritis program studies more than 4,900 patients with moderate-to-severe rheumatoid arthritis in six clinical trials.

At the annual meeting of the American Association for the Study of Liver Diseases, AbbVie presented new clinical data for the pan-genotypic chronic hepatitis C virus treatment Mavyret (glecaprevir/pibrentasvir) in treatment-naïve patients with compensated cirrhosis. Results from the Phase IIIb EXPEDITION-8 trial demonstrated that with eight weeks of Mavyret, 100 percent of genotype 1, 2, 4, 5, and 6 patients achieved a sustained virologic response 12 weeks after treatment per protocol analysis. The medication is already approved as an eight-week, pan-genotypic treatment for treatment-naïve patients without cirrhosis.

AbbVie and privately held immunotherapy company Tizona Therapeutics announced during December 2018 a global, strategic collaboration to develop and commercialize CD39-targeted therapeutics. The collaboration includes TTX-030, a first-in-class antibody for the treatment of cancer. The monoclonal antibody TTX-030 inhibits the activity of CD39, a cell surface enzyme upregulated on tumors, exhausted T cells, and many suppressive cell types as an immune evasion strategy.

The ATP-adenosine axis has recently emerged as a key immune regulatory switch in the tumor microenvironment (TME) by controlling immune cells’ inflammatory and suppressive activities. The CD39 enzyme is responsible for the initial steps in the conversion of immune stimulatory extracellular ATP to immune suppressive adenosine in the TME. CD39 inhibition with TTX-030 marks a novel and differentiated approach to targeting this pathway.



Alexion Pharmaceuticals pioneered the complex field of complement biology, and today the global biopharma company’s internal research efforts focus on leveraging more than 20 years of experience in this field. Alexion discovered and developed the world’s first complement inhibitor, Soliris (eculizumab), for treating life-threatening, ultra-rare disorders caused by uncontrolled complement activation. According to management, Alexion is now applying this deep expertise to pursue novel molecules and targets in the complement cascade.

Alexion’s development efforts concentrate on the core therapeutic fields of hematology, nephrology, neurology, and metabolic disorders. The company is working to expand Soliris into new complement indications and bolster the clinical-stage pipeline via internal and external development opportunities in four core areas: paroxysmal nocturnal hemoglobinuria/atypical hemolytic uremic syndrome (PNH)/aHUS, metabolics, neurology and anti-neonatal Fc receptor (FcRn).

As Alexion develops and delivers life-changing therapies, management is additionally leveraging a proprietary bioinformatics platform to strengthen the company’s understanding of rare diseases and provide insights into their epidemiology.

According to CEO Ludwig Hantson, Ph.D., “2018 was a transformational year for Alexion. I am proud of our many accomplishments, including entering rare neurology and making Soliris for gMG Alexion’s best launch ever, completing the Phase III program and launching Ultomiris for PNH in the U.S., delivering groundbreaking Phase III data and submitting regulatory filings for Soliris in NMOSD and rebuilding our pipeline through disciplined business development, all while continuing to grow our base business. As we look at 2019 and beyond, I am confident that this strong foundation positions us well to achieve our Four Pillars of growth, building durable, blockbuster franchises in PNH/aHUS, metabolics, neurology and FcRn.”

Alexion ended 2018 on a high note with the FDA marketing clearance of Ultomiris, which has the potential to become the new standard of care for both complement inhibitor-naïve patients and patients receiving the blockbuster medication Soliris, which generated 2018 global sales of $3.56 billion. As Alexion’s’ leading new product candidate during 2018, Ultomiris (ravulizumab-cwvz) is the first long-acting C5 complement inhibitor administered every eight weeks, for treating adults with PNH. A debilitating ultra-rare blood disorder, PNH is characterized by complement-mediated destruction of the red blood cells (hemolysis). The blood disorder can cause a wide range of debilitating symptoms and complications, such as thrombosis, which can occur throughout the body and lead to organ damage and premature death.

The U.S. marketing approval of Ultomiris arrived ahead of the Prescription Drug User Fee Act date of Feb. 18, 2019, which was set by the FDA as part of an expedited eight-month review following Alexion’s use of a rare disease priority review voucher.

Aplastic Anemia and Myelodysplastic Syndrome (AAMDS) International Foundation CEO Neil Horikoshi states, “The introduction of Soliris 11 years ago transformed the lives of patients with PNH. But the management of this debilitating disease still requires strength and sacrifice from patients and their families. With Ultomiris, patients no longer have to plan their lives around bi-weekly infusions and can look forward to just six or seven infusions a year.”

Regulatory authorities in the European Union and Japan have accepted and are reviewing applications for the marketing clearance of the monoclonal antibody Ultomiris for the treatment of adults with PNH.

A Phase 3 clinical study of Ultomiris in children and adolescents with PNH is under way.

The product is additionally being investigated in a Phase III trial in complement inhibitor-naïve patients with aHUS, administered intravenously every eight weeks. In January 2019, Alexion reported positive topline results from a Phase 3 trial in complement inhibitor naïve patients with aHUS. The clinical study met the primary objective with 53.6 percent of patients showing complete thrombotic microangiopathy (TMA) response. Based on these results, Alexion intends to submit for U.S. regulatory approval during first-half 2019 followed by the EU and Japan. Additionally, a Phase 3 trial of Ultomiris in adolescents and children with aHUS continues.

During late 2018, Alexion began a single, PK-based Phase 3 trial of the drug delivered subcutaneously once-weekly to support registration in PNH and aHUS. Clinical data are anticipated during early 2020.

Ultomiris has received Orphan Drug Designation for treating patients with PNH in the United States and European Union, and for the subcutaneous treatment of patients with aHUS in the U.S.

Alexion additionally intends to start during first-quarter 2019 Phase III development of the medicine, intravenously administered every eight weeks, as a potential treatment for patients with generalized MG (gMG).

Alexion is planning to initiate a Phase III trial of Ultomiris in neuromyelitis optica spectrum disorder (NMOSD).

Optum rated Ultomiris as one of five new and potentially expensive treatments that could make a large financial impact in 2019 and beyond. In November 2018 – before the product won FDA approval – EvaluatePharma analysts included Ultomiris as one of nine notable pipeline projects facing regulatory scrutiny in 2019, with the Alexion medicine having the highest consensus net present value ($10.9 billion) among them.

In other R&D news for Alexion, the company has filed U.S. and EU applications for the approval of eculizumab for NMOSD. These filings are based on previously announced results from the Phase III PREVENT trial, in which 97.9 percent of patients with anti-aquaporin-4 (AQP4) auto antibody-positive NMOSD receiving Soliris on top of stable standard-of-care therapy were free of relapse at 48 weeks versus 63.2 percent of patients receiving placebo. Alexion intends to submit for regulatory approval in Japan during 2019.

Enrollment is under way in a Phase III study of ALXN1840 (also known by the product code WTX101) in Wilson disease, which is a rare genetic disorder with devastating hepatic and neurological consequences. The clinical trial is now powered for superiority compared to standard-of-care therapy. ALXN1840 represents a first-in-class oral copper-binding agent with a unique mechanism of action to access and bind to serum copper and promote its removal from the liver.

During 2018, Alexion acquired WTX101 via the $855 million purchase of Swedish-based biopharmaceutical company Wilson Therapeutics. “The acquisition of Wilson Therapeutics is a key first step in rebuilding our pipeline,” Dr. Hantson noted. “We look forward to using our significant experience in rare metabolic and neurological diseases to improve treatment for patients with Wilson disease through the development of WTX101, which has the potential to be the first new treatment in more than 20 years and become the new standard of care for Wilson disease.”

WTX101 (bis-choline tetrathiomolybdate) has received Fast Track designation in the United States and Orphan Drug Designation for treating Wilson disease in the U.S. and EU. WTX101 represents a first-in-class copper-binding agent with a unique mechanism of action. In contrast to existing treatments, WTX101 provides an alternative copper-protein binding mechanism by forming a tripartite complex with copper and albumin. WTX101 thereby detoxifies excess copper in liver and blood, and promotes copper clearance via biliary excretion (the body’s natural route of elimination). WTX101 has a 10,000-fold higher affinity for copper than other chelators and addresses the underlying cause of Wilson disease.

In other M&A news for Alexion during 2018, the company in November completed the acquisition of Syntimmune at a potential transaction value of $1.2 billion. The acquisition added the clinical-stage anti-FcRn antibody SYNT001 to Alexion’s growing product pipeline. SYNT001 is the first anti-FcRn asset currently undergoing development for warm autoimmune hemolytic anemia (WAIHA). Alexion management expects to begin two pivotal studies in 2019 – one in WAIHA, following successful completion of the Phase 1b/2a study, and one in an undisclosed indication.

Alexion struck a deal in October 2018 with Dicerna Pharmaceuticals Inc. to discover and develop RNA interference (RNAi) therapies for complement-mediated diseases. An RNAi-based approach to blocking the production of complement pathway factors offers the potential to inhibit the uncontrolled complement activation that results in many diseases. The collaboration provides Alexion with exclusive global licenses as well as development and commercial rights for two of Dicerna’s preclinical, subcutaneously delivered GalXC RNAi molecules and an exclusive option for other preclinical GalXC RNAi molecules for two other targets within the complement pathway.



The clinical-stage biotechnology company Argenx is a first-time participant in this long-running annual report. With global headquarters in the Netherlands and a U.S. base in Boston, Argenx combines the diversity of the llama immune system with antibody engineering, advancing a clinical pipeline for treating patients with cancer and severe autoimmune diseases. The company’s platforms allow Argenx to unlock novel and complex targets as well as develop antibody-based drugs designed for greater efficacy and longer duration of effect.

Argenx creates antibodies with first-in-class and best-in-class therapeutic potential. The company has a deep pipeline of differentiated antibody-based therapies with one autoimmune asset in clinical phase, two potential oncology medicines in the clinic, and several product leads undergoing preclinical development.

Seeking Alpha analysts in December 2018 said “this below-radar Dutch company is a potential winner.” Since 2017 when Seeking Alpha started tracking the company through 2018, Argenx stock grew five-fold. According to the analysts, considering the company’s lead in myasthenia gravis, a collaboration with Janssen and so on, “Argenx has further upside potential.”

EvaluatePharma and Vantage analysts are high on two Argenx drug prospects, efgartigimod (consensus net present value: $6.5 billion) and cusatuzumab (consensus NPV: $3 billion). Each of these pipeline assets were highlighted in the “What to watch in 2019 – biopharma’s most valuable R&D projects” list from EvaluatePharma and Vantage in November 2018.

The lead horse is efgartigimod (product code ARGX-113), an investigational therapy for IgG-mediated autoimmune diseases that was designed to exploit the natural interaction between IgG antibodies and the recycling receptor FcRn. According to the company, efgartigimod is the Fc-portion of an IgG1 antibody that has been modified by the argenx proprietary ABDEG technology to increase its affinity for FcRn beyond that of normal IgG antibodies. As a result, efgartigimod blocks antibody recycling via FcRn binding and leads to fast depletion of the autoimmune disease-causing IgG autoantibodies. The development work on efgartigimod is performed in close collaboration with Professor E. Sally Ward from the University of Texas Southwestern Medical and Texas A&M University Health Science Center.

The investigational SIMPLE Antibody cusatuzumab (product code ARGX-110) targets CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors and severe autoimmune diseases. Cusatuzumab is designed to: block CD70, kill cancer cells expressing CD70 via complement dependent cytotoxicity, enhanced antibody-dependent cell-mediated phagocytosis and enhanced antibody-dependent cell-mediated cytotoxicity, and restore immune surveillance against solid tumors (Silence K. et al. mAbs 2014; 6 (2):523-532).

Cusatuzumab is undergoing clinical development in patients with hematological malignancies, including a Phase I/II study in combination with Vidaza in patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndromes, and the Phase II part of a Phase I/II study in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL). Preclinical work on cusatuzumab in acute myeloid leukemia (AML) was conducted in collaboration with the Tumor Immunology Lab of Professor A. F. Ochsenbein at the University of Bern, who won – together with Professor Manz at the University Hospital of Zürich – the prestigious 2016 Otto Naegeli Prize for his breakthrough research on CD70/CD27 signaling with therapeutic potential for cancer patients.

During December 2018, Argenx presented detailed Phase 2 ITP data demonstrating clear correlation between IgG reduction, platelet count increase and reduction of bleeding events. The ITP program is anticipated to advance to Phase III with IV efgartigimod and Phase II with a subcutaneous formulation. New cusatuzumab data in AML resulted in a 92 percent response rate with 10 of 12 patients demonstrating a complete response (CR/CRi).

“These datasets highlight the power of the collaborations we’ve forged with leading academic institutions,” says Argenx CEO Tim Van Hauwermeire. “As part of these collaborations, we combine our antibody discovery capabilities with our collaborators’ deep disease biology insights to together unravel the functions of novel targets. We have built our broad pipeline in this way and have demonstrated strong execution with each new product candidate we bring forward. Based on the clinically meaningful results and clean tolerability profiles we have observed to date, we believe we have two antibody molecules with efgartigimod and cusatuzumab that are both first-in-class and potentially best-in-class.”

According to Argenx Chief Medical Officer Nicolas Leupin, “We established strong proof-of-concept with efgartigimod in a second autoimmune indication showing a clear correlation between IgG reductions, platelet count increases and reduced bleeding events. The improvements in platelet counts were clinically meaningful in the treatment arms after a short drug exposure in a truly refractory ITP patient population. With these results and the drug candidate’s continued favorable tolerability, we look forward to advancing into a potential pivotal trial next year.

“We continue to be excited by the encouraging dataset from our Phase I/II trial of cusatuzumab in AML and MDS,” Leupin says. “This agent targets the CD70/CD27 pathway which has the potential to be a novel and selective mechanism in treating newly diagnosed AML patents regardless of age or cytogenetic profile. Today we are seeing a growing depth of responses from patients on cusatuzumab, with 10 out of 12 patients reaching complete response and eight of these 10 with hematologic recovery, which patients tolerated well. Six patients remain on trial, and we will watch as these data mature, including the durability of responses.”

Collaborations with pharma companies enable Argenx to provide expertise to partners and develop therapeutic antibody candidates in multiple disease fields. Management says Argenx is accessing truly novel targets via partnerships with academic research groups under the company’s Innovative Access Program.

Argenx struck a deal in December 2018 with Cilag GmbH International, an affiliate of the Janssen Pharmaceutical Companies of Johnson & Johnson. The two parties agreed on an exclusive, global collaboration and license deal for cusatuzumab for AML, MDS and other potential future indications. Janssen will pay Argenx $300 million up-front and Johnson & Johnson Innovation – JJDC Inc. (JJDC) will purchase $200 million of newly issued shares representing 4.68 percent of Argenx’s outstanding shares at a price of €100.02 per share ($113.19). Argenx is eligible to receive potentially up to $1.3 billion in development, regulatory and sales milestones, in addition to tiered, double-digit royalties. Janssen is responsible for global commercialization. Argenx retains the option to participate in U.S. commercialization efforts, where the companies have agreed to share economics 50/50 on a royalty basis. Outside the United States, Janssen will pay double-digit sales royalties to Argenx.

During third-quarter 2018, AbbVie exercised an exclusive option to license ARGX-115, a novel immuno-oncology antibody targeting glycoprotein A repetitions predominant (GARP). In another Q3 2018 transaction, Argenx received a preclinical milestone in the company’s strategic collaboration with Shire plc. The milestone, for which an undisclosed payment was received, was triggered by Shire exercising an exclusive option to in-license an antibody discovered and developed using Argenx’s proprietary SIMPLE Antibody platform and Fc engineering technologies.


BlueBird Bio

Making the company’s debut in Med Ad News’ Top 10 Pipelines To Watch annual report, Bluebird Bio is dedicated to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies. The clinical-stage company’s objective is to develop and bring to market the most advanced products based on the transformative potential of gene therapy to provide patients hope for a better life in the face of limited or no long-term safe and effective treatment options. With headquarters located in Cambridge, Mass., Bluebird Bio also has operations in Seattle; Durham, N.C.; and Zug, Switzerland.

According to company executives, Bluebird is leading the gene therapy revolution. The company’s integrated product platforms encompass gene therapy, cancer immunotherapy and gene editing – providing Bluebird with the potential to treat, and hopefully cure, a wide array of serious diseases. Bluebird is focused on developing products for treating cerebral adrenoleukodystrophy, transfusion-dependent β-thalassemia (also known as β-thalassemia major), multiple myeloma, and sickle cell disease.

Bluebird’s oncology pipeline is built upon the company’s lentiviral gene delivery and T cell engineering, with a concentration on developing novel T cell-based immunotherapies, such as chimeric antigen receptor (CAR T) and T cell receptor (TCR) therapies. The lead oncology programs are anti-B cell maturation antigen (BCMA) CAR-T programs in partnership with Celgene.

Bluebird’s discovery research programs include using megaTAL/homing endonuclease gene-editing technologies with potential use across the corporation’s product pipeline.

The potentially most lucrative pipeline assets in terms of commercial sales opportunity are bb2121 and LentiGlobin.

Bluebird and Celgene’s lead investigational anti-BCMA CAR-T cell therapy candidate for patients with relapsed and refractory multiple myeloma is bb2121. The new drug prospect is being developed as part of a joint-development, joint-promotion and profit-share deal between the two companies.

In November 2018, Bluebird and Celgene announced the completed enrollment for the KarMMa pivotal study of bb2121. KarMMa is a pivotal, open-label, single-arm, multi-center Phase II trial investigating the efficacy and safety of bb2121 in patients with relapsed and refractory multiple myeloma. During November 2017, bb2121 was granted Breakthrough Therapy Designation (BTD) by the U.S. FDA and PRIority Medicines (PRIME) eligibility by the European Medicines Agency. The BTD designation and PRIME eligibility were based on preliminary clinical data from the Phase 1 CRB-401 trial.

The FDA action date for the bb2121 New Drug Application is expected during 2020. “We continue to be excited about bb2121 as a potential first-in-class BCMA-targeted therapy for patients with multiple myeloma,” noted Alise Reicin, M.D., President, Global Clinical Development for Celgene.

LentiGlobin is a one-time gene therapy being evaluated as a potential treatment to address the underlying genetic cause of sickle cell disease (SCD), which could increase normal hemoglobin production. Bluebird’s clinical development program for LentiGlobin includes continuing studies globally with sites in Australia, Germany, Greece, France, Italy, Thailand, the United Kingdom and the United States. The company is also performing a long-term safety and efficacy follow-up study (known as LTF-303) for individuals who have participated in Bluebird-sponsored clinical trials of LentiGlobin for transfusion-dependent β-thalassemia (TDT) and SCD.

Bluebird during October 2018 reported that the European Medicines Agency (EMA) accepted the company’s Marketing Authorization Application (MAA) for LentiGlobin gene therapy for treating adolescents and adults with transfusion-dependent β-thalassemia (TDT) and a non-β0/β0 genotype. LentiGlobin was previously granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the EMA during July 2018, potentially reducing the regulatory body’s active review time of the MAA from 210 days to 150 days.

The EMA previously granted PRIME eligibility and Orphan Medicinal Product designation to LentiGlobin as a treatment for TDT. LentiGlobin is part of the EMA’s Adaptive Pathways pilot program, which is part of the European Union regulatory agency’s effort to improve timely access for patients to new medicines.

The U.S. Food and Drug Administration has granted LentiGlobin Orphan Drug status and Breakthrough Therapy designation for treating TDT.

Also, the EMA has granted Orphan Medicinal Product designation to LentiGlobin for treating SCD. LentiGlobin is part of the EMA’s Adaptive Pathways pilot program.

The U.S. FDA has granted LentiGlobin Orphan Drug status, Fast Track designation and Regenerative Medicine Advanced Therapy Designation as an SCD treatment.

During 2019, Bluebird Bio intends to start a Phase III trial of LentiGlobin in SCD.

Bluebird Bio and Celgene presented initial data from an ongoing Phase I study of the next-generation anti-BCMA CAR-T cell therapy bb21217 in patients with relapsed/refractory multiple myeloma (MM) at the ASH Annual Meeting in December 2018. According to the companies, bb21217’s early safety profile is consistent with CAR-T platform therapies and there was an 83 percent objective response rate in 12 heavily pretreated MM patients at the first dose level studied.

The investigational anti-BCMA CAR-T cell therapy bb21217 uses the bb2121 chimeric antigen receptor molecule with a manufacturing process designed to improve CAR-T cell functional persistence. According to researchers, bb21217 has exhibited improved functional persistence and increased anti-tumor activity in preclinical animal studies. The companies say bb21217 is being studied in the ongoing dose escalation part of the Phase I CRB-402 trial in adults with relapsed/refractory multiple myeloma who have received at least three prior treatments, including a proteasome inhibitor and immunomodulatory agent (or are double refractory).

According to Bluebird and Celgene, bb2121 and bb21217 are designed to recognize and kill plasma cells – notably malignant myeloma cells – that express the B cell maturation antigen. “Anti-BCMA CAR-T therapy with bb2121 has shown clinical responses in a substantial proportion of patients with relapsed/refractory multiple myeloma,” stated David Davidson, M.D., chief medical officer of Bluebird. “With the bb21217 program we are pursuing an approach intended to improve the in vivo persistence of functional CAR-T cells with the hope that this provides a more durable benefit for patients.”

Bluebird and the clinical-stage biotech company Inhibrx Inc. announced in January 2019 an exclusive license deal to research, develop and commercialize CAR-T cell therapies using Inhibrx’s proprietary single domain antibody (sdAb) platform to multiple cancer targets. The small size of sdAbs may allow for the generation of more complex CAR-T cell products including those designed to combine additional functions into a single CAR molecule or recognize multiple tumor antigens simultaneously.

Inhibrx is granting Bluebird the exclusive global rights to develop, manufacture and commercialize certain cell therapy products containing sdAbs directed to various cancer targets. Bluebird is responsible for the clinical development and commercialization of the cancer-targeting CAR-T products. According to Bluebird Bio Chief Scientific Officer Philip Gregory, D.Phil., “Access to the Inhibrx sdAb binder technology will allow us to combine the advancements we’ve made with our T cell therapy platform with their sdAb binder technology to generate novel cellular therapies with the potential to help patients in their fight against cancer. The technology from Inhibrx adds to our growing portfolio of tools and technologies that we can combine with our internal lentiviral vector, CAR and T cell expertise to discover potential new product candidates designed to recognize tumor-specific proteins expressed by cancer cells and kill them upon engagement.”


Bristol-Myers Squibb/Celgene

Two of the industry’s top 10 R&D spenders kicked off 2019 by announcing a mega-deal to combine forces. Bristol-Myers Squibb will acquire Celgene in a $74 billion cash and stock transaction to create a leading focused specialty biopharmaceutical company well-positioned to address the needs of patients with cancer, inflammatory and immunologic disease and cardiovascular disease via high-value innovative medicines and leading scientific capabilities.

Through the combination of the two businesses, management says the merged entity will “launch exciting new medicines for patients, including six expected near-term opportunities; advance a significantly enhanced early-stage pipeline; and integrate a broad range of discovery modalities that will further strengthen our pipeline.” Bristol-Myers Squibb will have significant financial flexibility to realize the full potential of the enhanced late-stage and early-stage pipeline.

“Together with Celgene, we are creating an innovative biopharma leader, with leading franchises and a deep and broad pipeline that will drive sustainable growth and deliver new options for patients across a range of serious diseases,” says Bristol-Myers Squibb Chairman and CEO Giovanni Caforio, M.D.

Creating the premier innovative biopharmaceutical company will significantly expand Bristol-Myers Squibb’s Phase III assets with six anticipated near-term product launches, representing more than $15 billion in revenue potential. The six near-term medicine opportunities consist of two in immunology and inflammation: TYK2 and ozanimod; and four in hematology: luspatercept, liso-cel (JCAR017), bb2121 and fedratinib. Management says these launches leverage the combined commercial capabilities of the two companies and will broaden and enhance Bristol-Myers Squibb’s market position with innovative and differentiated products. This is in addition to a significant amount of lifecycle management registrational readouts expected in Immuno-Oncology (IO). Liso-cel (JCAR017), ozanimod, bb2121, and luspatercept were listed as four of “What to watch in 2019 – biopharma’s most valuable R&D projects” in the Vantage 2019 Preview report issued in December 2018 by Vantage and Evaluate.

TYK2 is an intracellular signaling kinase that mediates cytokine-driven immune and pro-inflammatory signaling pathways that are critical in the cycle of chronic inflammation central to immune-mediated diseases. The novel, oral, selective TYK2 inhibitor BMS-986165 has a unique mechanism of action distinct from other kinase inhibitors, and is being clinically investigated by Bristol-Myers Squibb in a wide spectrum of immune-mediated diseases. BMS-986165 is undergoing a Phase 3 program for moderate-to-severe plaque psoriasis and Phase II studies for systemic lupus erythematosus and Crohn’s disease.

Celgene’s ozanimod is a novel, oral, selective, sphingosine 1-phosphate 1 (S1P1) and 5 (S1P5) receptor modulator undergoing development for immune-inflammatory indications including relapsing multiple sclerosis, ulcerative colitis and Crohn’s disease. Selective binding with S1P1 is thought to inhibit a specific sub set of activated lymphocytes from migrating to inflammation sites. The result is a reduction of circulating T and B lymphocytes that results in anti-inflammatory activity. Importantly, immune surveillance is maintained, according to researchers. Selective binding with S1P5 is believed to activate specific cells within the central nervous system. This process has the potential to enhance remyelination (when the body is able to repair damaged myelin after inflammation is reduced) and prevent synaptic defects. Ultimately, neurological damage may be prevented, researchers say.

Jointly developed via a worldwide collaboration between Celgene and Acceleron, luspatercept is a first-in-class erythroid maturation agent that is believed to regulate late-stage red blood cell maturation. Phase III programs continue to assess the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the MEDALIST trial) and in patients with beta-thalassemia (the BELIEVE study). Other studies under way inlcude the COMMANDS Phase III trial in first-line, lower-risk, MDS patients; the BEYOND Phase II study in non-transfusion-dependent beta-thalassemia; and a Phase II trial in myelofibrosis.

Liso-cel (JCAR017) is an investigational defined composition CD19-directed CAR-T cell product candidate using a 4-1BB costimulatory domain. The company’s lead CAR-T study, TRANSCEND NHL-001, is investigating liso-cel in adults with relapsed or refractory diffuse large B cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B, and mantle cell lymphoma. Celgene gained full global rights to JCAR017 upon completing the acquisition of Juno Therapeutics during March 2018. At the time of the $9 billion Juno acquisition announcement by Celgene, JCAR017 was hailed to be a significant growth driver beyond 2020 with potential global peak sales of $3 billion.

bb2121 is being developed as part of a joint-development, joint-promote and profit-share deal between Celgene and Bluebird Bio. The new drug compound represents a potential first-in-class BCMA-targeted therapy for patients with multiple myeloma. The companies’ lead investigational anti-BCMA CAR-T cell therapy candidate is intended for patients with relapsed and refractory multiple myeloma. The FDA action date for the bb2121 New Drug Application is on track for 2020.

When Celgene inked a deal in January 2018 to acquire Impact Biomedicines in a transaction valued at up to $7 billion, the Summit, N.J.-based integrated global biopharma company gained the development rights to fedratinib. The highly selective JAK2 kinase inhibitor was being developed by Impact Biomedicines for myelofibrosis and polycythemia vera. Fedratinib showed clinical improvement in a Phase III study with treatment-naïve myelofibrosis patients and in a phase II trial with myelofibrosis patients resistant or intolerant to Incyte Corp.’s JAK1/JAK2 inhibitor Jakafi (ruxolitinib).

Registrational clinical trial opportunities and the early-stage pipeline will position the combined company for sustained leadership underpinned by cutting-edge technologies and discovery platforms, executives note. Bristol-Myers Squibb/Celgene will have a deep and diverse early-stage pipeline across solid tumors and hematologic malignancies, immunology and inflammation, cardiovascular disease and fibrotic disease leveraging combined strengths in innovation. The early-stage pipeline includes 50 high-potential assets, many with important data readouts in the near term, according to management. With a significantly enhanced early-stage pipeline, Bristol-Myers will be well-positioned for long-term growth and significant value creation, the leadership team says.

Uniting the two corporations will result in powerful combined discovery capabilities with world-class expertise in a broad range of modalities. Bristol-Myers Squibb/Celgene will have expanded innovation capabilities in small-molecule design, biologics and synthetic biologics, protein homeostasis, antibody engineering and cell therapy. In addition, strong external partnerships will provide access to additional modalities.

The deep and broad late-stage pipeline through the Bristol-Myers Squibb and Celgene combo includes 10 Phase III assets. The robust mid-stage and early-stage pipeline of Phase I and Phase II assets includes 21 in oncology (with 10 for solid tumors), 10 in hematology, 10 in immunology and inflammation, and nine in cardiovascular/fibrosis.

Bristol-Myers/Celgene will have nine products with more than $1 billion in yearly sales and significant potential for growth in the core disease areas of oncology, immunology, and inflammation, and cardiovascular disease. The combination creates leading oncology franchises in solid tumors and hematologic malignancies led by Opdivo and Yervoy as well as Revlimid and Pomalyst; a top five immunology and inflammation franchise headed by Orencia and Otezla; and the No. 1 cardiovascular franchise led by Eliquis. At the time of the merger announcement, each of those seven blockbusters were undergoing clinical development for new indications.



Another newcomer to appear in this annual report is FibroGen, which is dedicated to creating innovative, first-in-class medicines for treating chronic and life-threatening or debilitating conditions including anemia in chronic kidney disease (CKD), anemia in myelodysplastic syndromes (MDS), idiopathic pulmonary fibrosis (IPF), pancreatic cancer, and Duchenne muscular dystrophy (DMD). According to management, the products FibroGen develops represent more than isolated opportunities or single indications – the company sees its products as representing broader platforms that enable researchers to continue to investigate discrete pathways and mediators that are central to multiple diseases.

The San Francisco-based corporation is applying deep expertise in the biology of the body’s central mediators and internal pathways to build a biopharma company with a strong product pipeline, offering new approaches to the treatment of anemia, fibrosis, cancer, corneal blindness and other serious medical conditions. According to company executives, China is a critical part of FibroGen’s strategy and commitment to deliver groundbreaking therapies for serious diseases.

FibroGen’s near-term and long-term strategies include:

• Advancing roxadustat through approval and commercial launch in collaboration with FibroGen’s pharma partners for treating anemia in CKD.
• Initiating roxadustat pivotal studies for the treatment of anemia in MDS in China, the United States, and Europe.
• Completing Phase 2 studies of pamrevlumab in idiopathic pulmonary fibrosis and pancreatic cancer, and advancing to Phase III pivotal trials for each indication.
• Developing a proprietary biosynthetic cornea, FG-5200, for treating corneal blindness in China and other countries.
• Investing strategically in R&D to expand roxadustat into additional anemia indications and to expand pamrevlumab into other fibrotic and proliferative diseases, including Duchenne muscular dystrophy.
• Maintaining an extensive and multi-layered patent portfolio to protect the company’s technologies and product candidates.

FibroGen’s proprietary programs directly result from the company’s investment into scientific exploration of these critical targets and pathways. FibroGen’s hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) platform builds off of the discovery that a family of prolyl hydroxylase enzymes is involved in regulating HIF and HIF-mediated pathways. According to FibroGen, this insight has allowed the company to investigate the ability of roxadustat and other proprietary compounds to therapeutically harness the body’s own natural responses. Through the company’s pamrevlumab platform, FibroGen is advancing therapeutic applications that target connective tissue growth factor (CTGF), a central mediator of fibrotic and proliferative disease, as a regulator of extracellular matrix production. The company is also investigating the use of FG-5200, a biosynthetic cornea manufactured from proprietary recombinant human collagen, in treating corneal blindness.

FibroGen announced during December 2018 positive topline results from three global Phase III studies of the company’s lead drug candidate roxadustat, intended for the treatment of anemia in patients with chronic kidney disease. The HIF-PHI inhibitor met all primary efficacy endpoints in the three global pivotal Phase III studies carried out by FibroGen: ANDES in non-dialysis-dependent chronic kidney disease patients, HIMALAYAS in incident (newly initiated) dialysis patients, and SIERRAS in dialysis-dependent CKD patients. Each study had a pre-specified primary efficacy endpoint for meeting U.S. regulatory requirements and another pre-specified primary efficacy endpoint for meeting EU regulatory requirements, which additionally served as a secondary efficacy endpoint for the United States. The U.S. and EU primary efficacy endpoints were met in all three studies.

According to FibroGen CEO Thomas B. Neff, “These Phase III results demonstrate the potential for roxadustat to be a first-in-class oral anemia therapeutic for CKD patients. This is the first well-controlled CKD anemia program that has shown improved efficacy in incident and stable dialysis patients relative to ESA standard of care therapy.”

Discovered by FibroGen, roxadustat (product code FG-4592) is a first-in-class, orally administered small molecule marketed in China for treating anemia in CKD patients on dialysis. Roxadustat is a HIF-PHI that promotes erythropoiesis by way of increasing endogenous production of erythropoietin, improving iron regulation, and overcoming the negative impact of inflammation on hemoglobin syntheses and red blood cell production by downregulating hepcidin. Administration of roxadustat has been demonstrated to induce coordinated erythropoiesis, increasing red blood cell count while maintaining plasma erythropoietin levels within or near normal physiologic range in multiple subpopulations of CKD patients, including in the presence of inflammation and without a need for supplemental intravenous iron.

FibroGen and collaboration partners are pursuing four approval pathways in major jurisdictions to prepare for global commercialization. FibroGen and Astellas are collaborating on the development and commercialization of roxadustat for treating anemia in territories including Japan, Europe, the Commonwealth of Independent States, the Middle East, and South Africa. AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat for anemia treatment in the United States, China, and other markets in the Americas and in Australia/New Zealand as well as Southeast Asia.

FibroGen and the company’s partners have completed 35 Phase I and Phase II trials. The Phase II trials have consistently shown anemia correction and maintenance of hemoglobin levels in multiple subpopulations across a wide spectrum of CKD patients.

On a worldwide scale, the Phase III program encompasses a total of 15 Phase III trials of roxadustat in non-dialysis-dependent and dialysis-dependent CKD patients to support independent regulatory approvals in the United States, Europe, Japan, and China. As of Dec. 20, 2018, positive topline results had been reported for 12 of the Phase III studies, with two supporting the China NDA for treating anemia in CKD patients on dialysis and not on dialysis, four supporting the Japan NDA for treating anemia in CKD patients on dialysis, and six supporting the U.S./EU submissions. Roxadustat was approved by China National Medical Products Administration (NMPA) during December 2018 as a treatment for anemia in CKD patients on dialysis. The Japan NDA filed by Astellas is undergoing regulatory review by the Japan Pharmaceuticals and Medical Devices Agency.

Roxadustat is undergoing Phase III clinical development as a treatment for anemia associated with MDS in the United States and in Phase II/III studies for MDS in China.

The first-in-class antibody pamrevlumab is being developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. The new drug candidate is advancing towards Phase III studies for treating idiopathic pulmonary fibrosis (IPF) and pancreatic cancer, with Orphan Drug Designation having been granted in each of these indications. Pamrevlumab is also undergoing a Phase II trial for Duchenne muscular dystrophy. Pamrevlumab has been granted Fast Track designation from the U.S. Food and Drug Administration for treating patients with IPF and also for locally advanced unresectable pancreatic cancer.

Across all clinical studies, pamrevlumab has consistently shown a good safety and tolerability profile, according to FibroGen. Company management anticipated advancing the anti-CTGF antibody pamrevlumab into Phase III trials during early 2019.



Gilead is responsible for two of the best-selling pharmaceutical product launches of all-time: the hepatitis C treatments Harvoni and Sovaldi. Gilead also has a variety of blockbuster products in the HIV space, including sales-growth generators Genvoya, Odefsey, Descovy, and Biktarvy. Gilead also brought to market the blood cancer drug Yescarta as the second-ever gene therapy and chimeric antigen receptor T-cell (CAR-T) therapy to receive U.S. regulatory approval, via the company’s acquisition of Kite Pharma. While still focusing on products in the HIV, oncology and hepatitis settings, Gilead’s pipeline is also targeting some newer areas of interest for the company, including inflammatory diseases and nonalcoholic steatohepatitis (NASH).

Gilead is advancing a pipeline of novel investigational agents for inflammatory diseases, addressing multiple targets with potential application across a broad range of disorders. The lead product candidate in this area for Gilead is the highly selective JAK1 inhibitor filgotinib. According to EvaluatePharma, the consensus net present value for filgotinib as of November 2018 was $6.6 billion.

Gilead and Galapagos are globally collaborating on the development and commercialization of filgotinib in inflammatory indications. Clinical trials include the FINCH Phase III program in rheumatoid arthritis; the DIVERSITY Phase III study in Crohn’s disease; the Phase IIb/III SELECTION study in ulcerative colitis; and Phase II trials in small bowel and fistulizing Crohn’s disease, psoriatic arthritis, ankylosing spondylitis, Sjogren’s syndrome, lupus and uveitis.

Filgotinib was discovered and developed by Galapagos using the clinical-stage biotech company’s target and drug discovery technology platform. In more than 1,600 patient years of rheumatoid arthritis and Crohn’s disease clinical trial experience, filgotinib has demonstrated a rapid onset of action, potentially best-in-class efficacy and favorable findings on safety and tolerability.

Galapagos and Gilead entered into a global collaboration pact during December 2015 to develop and commercialize filgotinib for treating inflammatory indications. Under the terms of the collaboration, Gilead is mainly responsible for development and for seeking regulatory approval of the licensed product. Galapagos is responsible for jointly funding 20 percent of development costs through to regulatory marketing clearance.

Gilead and Galapagos during October 2018 reported detailed results from the Phase III FINCH 2 study of filgotinib in adults with moderately to severely active rheumatoid arthritis and prior inadequate response or intolerance to biologic agents. The clinical data suggest that filgotinib has a potential role in addressing significant unmet needs in treating rheumatoid arthritis. Positive efficacy data from FINCH 2 were previously revealed during September 2018. The data demonstrate statistically significant improvements in the proportion of patients achieving a range of clinical efficacy endpoints. Other FINCH 2 data include positive results across several patient-reported health-related quality-of-life measures.

FINCH 2 was a global, 24-week, randomized, double-blind, placebo-controlled, Phase III trial investigating daily oral filgotinib on a background of conventional synthetic disease-modifying anti-rheumatic drug(s) (csDMARDs) in adults with moderately to severely active rheumatoid arthritis who had not adequately responded (or were intolerant) to prior biologic DMARDs (bDMARDs).

“We are encouraged by these data, which suggest filgotinib can improve symptoms of rheumatoid arthritis in patients who have not responded to prior biologic treatment and who need new therapies that are safe and effective,” noted Galapagos Chief Medical Officer Walid Abi-Saab, M.D.

In what could be a $35 billion market for drug companies, Gilead’s lead NASH candidate is the Phase III asset selonsertib. According to EvaluatePharma, interim data from selonsertib’s Stellar-3 and Stellar-4 clinical studies are expected during first-half 2019, with Gilead management hoping to seek accelerated approval based on fibrosis endpoints.

Gilead and Yuhan Corporation announced in January 2019 a licensing and collaboration agreement to jointly develop novel therapeutic candidates for treating patients with advanced fibrosis due to NASH. Gilead will acquire worldwide rights to develop and commercialize novel small molecules against two undisclosed targets in all countries, with the exception of the Republic of Korea where Yuhan will retain certain commercialization rights. Yuhan and Gilead will jointly perform preclinical research, with Gilead responsible for worldwide clinical development. Gilead is responsible for commercialization globally, outside of Yuhan’s rights in the Republic of Korea.

Gilead and Agenus Inc. entered into a partnership during December 2018 that is concentrating on the development and commercialization of up to five novel immuno-oncology therapies. Gilead receives global exclusive rights to AGEN1423, which had an estimated IND filing by year-end 2018. Gilead receives the exclusive option to license two other programs: AGEN1223 and AGEN2373. Agenus has submitted the IND for AGEN1223 and has an estimated IND filing for AGEN2373 in first-half 2019. Agenus is responsible for developing the option programs up to the option decision points, at which time Gilead may obtain exclusive rights to the programs on option exercise. For one of the option programs, Agenus has the right to opt into shared U.S. development and commercialization. Gilead receives right of first negotiation for two other, undisclosed preclinical programs.

In another December 2018 deal, Gilead and Scholar Rock Holding Corporation agreed on a strategic collaboration to discover and develop highly specific inhibitors of transforming growth factor beta (TGFβ) activation for the treatment of fibrotic diseases. Gilead has exclusive options to license global rights to product candidates that emerge from three Scholar Rock TGFβ programs: inhibitors that target activation of latent TGFβ1 with high affinity and specificity, inhibitors that selectively target activation of latent TGFβ1 localized to extracellular matrix, and a third TGFβ discovery program. Scholar Rock is responsible for antibody discovery and preclinical research through product candidate nomination, after which – upon exercising the option for a program – Gilead is responsible for the program’s preclinical and clinical development and commercialization. Scholar Rock retains exclusive global rights to discover, develop, and commercialize certain TGFβ inhibitors for oncology and cancer immunotherapy.

Gilead and Tango Therapeutics Inc. in October 2018 inked a worldwide strategic collaboration to discover, develop and commercialize a pipeline of innovative targeted immuno-oncology treatments for cancer patients. Under the multi-year collaboration, Tango will perform target discovery and validation while Gilead will have options to global rights on up to five targets emerging from Tango’s proprietary functional genomics-based discovery platform. For two programs directed to these targets, Tango will retain the option to jointly develop and co-detail in the United States.

Kite Pharma and biotechnology company HiFiBiO Therapeutics announced a research collaboration and license agreement in October 2018 to develop technology supporting the discovery of neoantigen-reactive T cell receptors (TCRs) for the potential treatment of various cancers, including solid tumors. The companies plan to adapt HiFiBiO’s proprietary single cell technology platform to create a high-throughput approach that will potentially allow for the in-depth screening of TCR repertoires from patient samples to identify shared antigen and neoantigen TCRs for use in adoptive cellular therapies. According to researchers, neoantigens arise from tumor-specific mutations that are unique to each patient’s cancer, offering the potential for more targeted antitumor activity. Kite has an exclusive option to license the HiFiBiO platform to screen T cell repertoires and to identify TCRs for use in TCR engineered T cell therapies with a corresponding payment to HiFiBiO.



GlaxoSmithKline significantly bolstered the company’s pharmaceutical business recently and accelerated the build of GSK’s pipeline and commercial capability in oncology with the acquisition of Tesaro. The acquisition of the oncology-focused biopharmaceutical company, which was announced on Dec. 3, 2018, was completed on Jan. 22, 2019. Waltham, Mass.-based Tesaro was purchased for an aggregate cash consideration of £4.0 billion ($5.1 billion).

A commercial-stage biopharmaceutical company, Tesaro’s major marketed product Zejula (niraparib) is an oral poly ADP ribose polymerase (PARP) inhibitor approved for use in ovarian cancer. PARP inhibitors are transforming the treatment of ovarian cancer, notably showing marked clinical benefit in patients with and without germline mutations in a BRCA gene (gBRCA). Zejula is available in the United States and Europe for treating adults with recurrent ovarian cancer who are in response to platinum-based chemotherapy, regardless of BRCA mutation or biomarker status.

Clinical studies to assess the use of Zejula in “all-comers” patient populations, as a monotherapy and in combinations, for the significantly larger opportunity of first-line maintenance treatment of ovarian cancer are additionally under way. These trials are studying the potential benefit of Zejula in patients who carry gBRCA mutations as well as the larger population of patients without gBRCA mutations whose tumors are HRD-positive and HRD-negative. Results from the first of these clinical trials, PRIMA, are anticipated during second-half 2019.

GSK management believes that PARP inhibitors offer significant opportunities for use in treating multiple cancer types. In addition to ovarian cancer, Zejula is being evaluated for use as a possible treatment in lung, breast and prostate cancer, both as a monotherapy and in combination with other medicines, including with Tesaro’s own anti-PD-1 antibody dostarlimab (formerly known as TSR-042). Tesaro has several oncology assets in the company’s pipeline in addition to Zejula and dostarlimab, including antibodies directed against TIM-3 and LAG-3 targets.

According to GlaxoSmithKline Chief Scientific Officer and President of R&D Hal Barron, M.D., “Both GSK and Tesaro are driven by a focus on patients and a deep desire to develop truly transformational medicines that can improve and extend their lives. The acquisition of Tesaro, which we have completed today [Jan. 22], significantly strengthens our oncology pipeline and brings new scientific capabilities and expertise that will increase the pace and scale at which we can help patients living with cancer.”

GSK concentrates on delivering transformational therapies for cancer patients that may help to maximize their survival. The company’s pipeline is focused on immuno-oncology, cell therapy, and epigenetics. “Our goal is to achieve a sustainable flow of new treatments for cancer patients based on a diversified portfolio of investigational medicines utilizing modalities such as small molecules, antibodies, multi-specific molecules, adjuvants and cells, either alone or in combination,” management says.

According to EvaluatePharma analysts, GSK’s anti-B-cell maturation antigen (BCMA) antibody-drug conjugate GSK2857916 registered a net present value (NPV) of $5.4 billion as of November 2018. That figure places GSK2857916 as No. 8 in terms of NPV among EvaluatePharma’s 2019 “biopharma’s most valuable R&D projects.”

GSK2857916 is a humanized anti-CMA monoclonal antibody conjugated to the cytotoxic agent monomethyl auristatin-F, via non-cleavable linker – the drug linker technology is in-licensed from Seattle Genetics. GSK2857916 has received Breakthrough Therapy Designation/PRIME designation and Orphan Drug Designation from the European Medicines Agency and U.S. FDA for the treatment of relapsed and refractory multiple myeloma.

During October 2018, the Phase II study of GSK’916 in combination with standard of care in second-line multiple myeloma was initiated; primary results are anticipated in 2020. Interim data from this clinical trial will be used to inform the beginning of two Phase III studies in second-line multiple myeloma during 2019.

“Overall, with three pivotal stage assets which have potential to launch within the next few years, and 12 other assets in the clinic, GSK’s oncology pipeline is gaining strength, and will start to impact our revenue growth outlook from next year,” said GlaxoSmithKline CEO Emma Walmsley at the J.P. Morgan Healthcare Conference during January 2019.

As GlaxoSmithKline bolsters the company’s cancer pipeline, GSK also continues to develop new treatments for the HIV marketplace. Another highly anticipated product in the GSK pipeline is a combination of two already-marketed HIV medicines: the integrase strand transfer inhibitor Tivicay (dolutegravir) and the nucleoside analog Epivir (lamivudine). During October 2018, ViiV Healthcare announced the submission of a New Drug Application to the U.S. FDA for a single-tablet, two-drug regimen of dolutegravir (DTG) and lamivudine (3TC) for treating HIV-1 infection. The NDA filing is based on the worldwide GEMINI 1 & 2 clinical trials that included more than 1400 HIV-1 infected adults with baseline viral loads up to 500,000 c/mL. ViiV is a global specialist HIV company majority owned by GlaxoSmithKline, along with Pfizer and Shionogi.

A priority review voucher was filed with the U.S. regulatory agency along with the NDA. Under the Prescription Drug User Fee Act, the anticipated target action date for this NDA with a priority review voucher is six months after FDA’s receipt of the application. U.S. marketing clearance is expected in second-quarter 2019. An MAA to the European Medicines Agency was filed during September 2018, and EU FDC approval is anticipated during third-quarter 2019. Other global regulatory submissions for DTG and 3TC as a single-tablet, two-drug regimen for HIV-1 therapy are planned.

According to GSK, both oral and long-acting injectable two-drug regimens could provide options for patients to reduce drug burden by ~20,000 doses over a lifetime. In addition to dolutegravir + lamivudine, the long-acting injectable two-drug regimen cabotegravir + rilpivirine represents a new treatment paradigm in HIV. The investigational, long-acting, injectable regimen is being jointly developed as part of a collaboration between ViiV and Janssen Sciences Ireland.

Cabotegravir is an investigational integrase strand transfer inhibitor. The non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine is marketed as Edurant in combination with other antiretroviral agents for the treatment of HIV-1 infection.

At the end of October 2018, positive 48-week results were reported for FLAIR, the second global Phase III trial of cabotegravir + rilpivirine. The FLAIR study met the primary endpoint, demonstrating similar efficacy of a once-a-month, investigational, injectable two-drug regimen of cabotegravir and rilpivirine versus a daily, oral three-drug, integrase-based regimen in virally suppressed adults. In August 2018, positive headline results from the worldwide, Phase III ATLAS trial of cabotegravir + rilpivirine were reported.

GSK anticipates FDA marketing approval for cabotegravir + rilpivirine during first-quarter 2020. “This innovative dosing regimen could transform HIV therapy by reducing the number of days a person receives treatment from 365 to 12,” says ViiV Chief Scientific and Medical Officer John C. Pottage Jr., M.D.



Novartis took strong action to focus the company and its capital towards the Innovative Medicines Division throughout 2018, resulting in an industry-leading pipeline, according to company management. During November 2018, Novartis provided an R&D update highlighting a product pipeline with potential blockbusters and advanced therapy platforms: 26 potential blockbusters in confirmatory development; 13 projects in clinical development across Cell, Gene & Radioligand therapies; and 60 major filings planned from 2019 to 2021.

Novartis is advancing a pipeline of medicines with potential to alter the standard of care in high-burden disease fields. In multiple sclerosis, Mayzent (siponimod, formerly BAF312) is anticipated to launch during first-quarter 2019 as the first drug proven to delay progression for typical patients living with secondary progressive multiple sclerosis (SPMS). Siponimod has been developed as an investigational, selective modulator of specific subtypes of the sphingosine-1-phosphate (S1P) receptor. According to the “EvaluatePharma World Preview 2018, Outlook to 2024” report, Mayzent is predicted to generate $1.54 billion in 2024 worldwide sales.

The MS drug ofatumumab (OMB157) is a next-generation B-cell depletor with a potentially favorable safety profile from faster b-cell repletion and preserved immunity, and with a convenient monthly subcutaneous dosing.

In moderate-to-severe asthma, QAW039 (fevipiprant) is targeting a unique profile of biologic efficacy with oral simplicity.

In neovascular age-related macular degeneration, brolucizumab (RTH258) has the potential to reduce treatment burden by drying the retina better with fewer injections. A humanized single-chain antibody fragment (scFv), brolucizumab represents the most clinically advanced, humanized single-chain antibody fragment to reach Phase III development. EvaluatePharma analysts have projected global sales of $1.8 billion for the product in 2024.

In sickle cell disease, SEG101 (crizanlizumab) is a promising treatment with data from a pivotal clinical study demonstrating patients have more vaso-occlusive crisis-free days. Sickle cell vaso-occlusive crises (VOCs) are triggered by multi-cell adhesion or clusters of cells that block or reduce blood flow, and are associated with increased morbidity and mortality. The Food and Drug Administration during January 2019 granted crizanlizumab Breakthrough Therapy Designation for the prevention of VOCs in patients of all genotypes with sickle cell disease. The humanized anti-P-selectin monoclonal antibody is being developed as a monthly infusion. Regulatory submissions are expected in 2019, including in the United States during the first half.

In lung cancer, ACZ885 (canikinumab) is undergoing three Phase lll trials in adjuvant NSCLC, first-line NSCLC, and second-line NSCLC with an opportunity to become the standard of care in these settings.

Progressing cell, gene, and radioligand therapy platforms with 13 therapies in clinical development, nine more are expected by Novartis to enter the clinic during 2019. According to the company, the potentially foundational gene therapy AVXS101 – now known as Zolgensma – delivers rapid, transformational and durable benefit in SMA Type 1. Zolgensma represents the first in a proprietary platform for the treatment of rare, monogenic diseases using gene replacement therapy – technology that replaces a missing or defective gene with a functional copy to correct the underlying cause of genetic disease. Regulatory approvals for the new drug candidate are expected in the United States, EU, and Japan during first-half 2019.

In Radioligand therapy, Novartis acquired Advanced Accelerator Applications (AAA) and successfully launched Lutathera in neuroendocrine tumors (NET) and has projects undergoing development for indications beyond NET. AAA’s Lutathera represents the first Peptide Receptor Radionuclide Therapy (PRRT) to receive regulatory registration, with approval by the European Commission during September 2017 and by the U.S. FDA in January 2018.

Novartis’ acquisition of Endocyte, which was completed in December 2018, has strengthened the company’s leadership in nuclear medicine and radioligand therapy for treating cancer in addition to complementing the robust AAA radioligand therapy pipeline. The U.S.-based biopharmaceutical company Endocyte has focused on developing radioligand and CAR-T therapies for cancer treatment. The acquisition adds to the Novartis portfolio 177Lu-PSMA-617, a potential first-in-class radioligand therapy in Phase III development for metastatic castration-resistant prostate cancer (mCRPC).

Novartis also highlights one of the most comprehensive CAR-T development programs across multiple indications.

Maximizing the potential of in-line brands with new data is a key development priority for Novartis. The company is pursuing new indications and building out the data profile for the blockbuster medications Cosentyx (secukinumab), Entresto (sacubitril/valsartan) and Gilenya (fingolimod). Cosentyx is expected to be Novartis’ top-selling drug during 2019, with robust growth in all three approved indications: plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. According to management, confidence in Cosentyx stems from 100 studies and an extensive Phase III clinical trial program, including PREVENT in non-radiographic axial spondyloarthropathy, a potential fourth indication. Entresto’s position in heart failure with reduced ejection fraction (HFrEF) is being bolstered by new clinical data that could increase initiation of therapy in hospitals. Entresto additionally has the potential to be the first approved treatment for heart failure with a preserved ejection fraction (HFpEF) with the PARAGON-HF study, with results expected in 2019. The oral MS therapy Gilenya continues to benefit from a wealth of data flow, including a recent approval for pediatric use as well as the ASSESS clinical trial that demonstrated superiority to Copaxone.



Boston-based Vertex Pharmaceuticals returns to the Med Ad News “Top 10 Pipelines To Watch” listing after last appearing in the 2016 edition. According to the biotechnology company’s leadership team, “At Vertex, we are relentless in our pursuit to create transformative medicines. We have spent the last 20 years doing what was once thought impossible – developing the first medicines that treat the underlying cause of CF. The price of our medicines reflects the significant value they bring to patients and our commitment to continuing to invest in the development of new medicines for those still waiting.”

Vertex’s cystic fibrosis program started as a small research project during 1998. Now, the company has the most cystic fibrosis compounds in clinical development in the industry, and is focused on developing medicines for all people with CF.

Vertex markets the blockbuster CF medicines Kalydeco (ivacaftor) and Orkambi (lumacaftor/ivacaftor). The oral drug Kalydeco represents the first medicine to treat the underlying cause of CF in people with specific mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF results from a defective or missing CFTR protein due to mutations in the CFTR gene. Orkambi combines lumacaftor, which is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del-CFTR protein, and ivacaftor, which enhances the function of the CFTR protein once it reaches the cell surface.

The company is developing a new combination medicine for CF that is heralded by healthcare analysts as representing the highest-grossing R&D product in the industry. According to EvaluatePharma and Vantage analysis, Vertex’s triple combination VX-659 + tezacaftor + ivacaftor is the most valuable project in the pharma industry pipeline with a net present value of $14.4 billion (as of November 2018).

Near the end of November, Vertex unveiled that two Phase III studies of the triple combination of VX-659, tezacaftor, and ivacaftor met the primary endpoint of improvement in lung function (ppFEV1) in people with cystic fibrosis. The next-generation corrector VX-659, tezacaftor, and ivacaftor resulted in statistically significant improvements in lung function (percent predicted forced expiratory volume in one second, or ppFEV1) in two Phase III trials in CF patients.

According to the company, the triple combo regimen’s safety and efficacy profile supports potential submission of an NDA. Two Phase III trials of VX-659, tezacaftor, and ivacaftor are fully enrolled, with clinical data anticipated in first-quarter 2019.

Vertex is also conducting two Phase 3 studies for a triple combination of the next-generation corrector VX-445, tezacaftor and ivacaftor in people with CF with one F508del mutation and one minimal function mutation and in people with two F508del mutations. The clinical data expected during the first quarter of 2019 for VX-445 and the data reported on Nov. 27 for VX-659 will allow Vertex to choose the best regimen to file for potential regulatory approvals worldwide and will provide the basis for potential submission of an NDA for the triple combo regimen to the U.S. FDA no later than mid-2019.

Clinical data from the studies of VX-659 and VX-445 will additionally be used for regulatory filings outside of the U.S. planned for late 2019.

“These data mark a major milestone in our efforts to develop new CF medicines as they underscore the important clinical benefit that a triple combination regimen may provide to the vast majority of CF patients who have at least one F508del mutation,” noted Reshma Kewalramani, M.D., executive VP, Global Medicines Development and Medical Affairs and chief medical officer at Vertex.

The data announced in November 2018 for people ages 12 and older with one F508del mutation and one minimal function mutation are from a continuing Phase III trial investigating VX-659/tezacaftor/ivacaftor versus placebo for 24 weeks.

Vertex initiated the company’s CF research program during 2000 as part of a collaboration with CFFT, a nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Kalydeco, Orkambi, Symdeko (tezacaftor/ivacaftor and ivacaftor), VX-659, and VX-445 were discovered by Vertex as part of the collaboration.

Clinical trials are under way to study both the VX-659 and VX-445 triple combination regimens in children with CF ages 6 through 11 who have one F508del mutation and one minimal function mutation and in children who have two F508del mutations. These studies are intended to support potential approval of a triple combo regimen in children ages 6-11 years.

Vertex continues to invest to discover and develop transformative medicines in other serious diseases, such as the development of the autologous gene-edited hematopoietic stem cell therapy CTX001 for treating β-thalassemia and sickle cell disease. At the beginning of 2019, Vertex and CRISPR Therapeutics reported that the U.S. FDA granted Fast Track Designation for CTX001 for treating sickle cell disease (SCD). CTX001 is intended for patients suffering from severe hemoglobinopathies. Phase I/II trials for SCD and β-thalassemia are under way.

Vertex expects data during first-half 2019 from a Phase IIb dose-ranging trial investigating the Nav1.8 inhibitor VX-150 using an oral form in patients with acute pain following bunionectomy surgery. The study is designed to assess multiple oral doses of VX-150 to potentially support pivotal development in acute pain. Vertex is conducting a third Phase II proof-of-concept trial studying VX-150 for treating pain caused by small fiber neuropathy, with positive results reported during December 2018.

The company has advanced multiple small-molecule correctors of alpha-1 antitrypsin (AAT) through preclinical development, and in December 2018 began clinical development for the first of these potential medicines. AAT is a genetic disorder resulting from mutations in a single gene that lead to life-shortening systemic complications, primarily in the lung and liver.

In early January 2019, Vertex and Arbor Biotechnologies established a collaboration to discover novel proteins to advance the discovery of gene-editing therapies. The multi-year research deal is being funded by Vertex using Arbor’s proprietary research platform to enhance efforts in developing gene-editing therapies in five diseases. The collaboration will concentrate on the discovery of novel programmable DNA endonucleases or nickases with high fidelity and catalytic activity as well as novel transduction approaches.

“We believe that by using our powerful biodiscovery platform we will be able to identify complementary and next generation tools to enhance Vertex’s pipeline of transformative medicines and new gene-editing therapies,” stated Arbor Co-Founder David Walt, Ph.D.

Vertex and Genomics plc during August 2018 formed a collaboration to use human genetics and data science to advance the discovery of precision medicines. The multi-year collaboration joins together expertise in genomics, machine learning and drug discovery to identify novel targets for innovative medicines. The goal is to further advance Vertex’s efforts to develop transformative precision medicines for patients with serious diseases.

Genomics has developed a unique analysis engine, which uses genetics to understand human biology and the likely efficacy and safety of potential novel drugs. The Genomics engine is the largest of its kind worldwide, with more than 100 billion data points. The Genomics engine links human genetic variation at more than 14 million positions in the human genome to changes in 7,000 molecular, cellular, and physiological measurements and disease outcomes. The company uses proprietary machine learning and statistical algorithms to predict the impact of therapeutic interventions.