This yearly review analyzes recent developments, trends and outlooks in the areas of biotechnology, biosimilars, biopharmaceuticals, biologics, biomarkers and biobanks.
Big deals in 2018
With many big deals already on the ledger this year, 2018 is on track to be a popular one in terms of M&A activity in the biotech/biopharma world. With key drugs dealing with lower sales due to patent cliffs and increased competition, the big players in the pharma and biotech space are looking to build their pipelines with new prospects to boost growth. Also helping fuel the acquisition pace is tax reform that enables companies to pay less in corporate taxes and repatriate cash at a reduces rate.
2017 was regarded as a lackluster year on the merger and acquisition front in the pharma/biotech world by many industry analysts. “The strength exhibited by biopharma shares in 2017 is perhaps surprising when considering the failure of M&A action to pick up. Widely considered a driver of investor enthusiasm, takeover activity actually dimmed over the year,” according to the EP Vantage Pharma, Biotech & Medtech 2017 in review report.
“A paltry 179 deals were struck, raising just $80 billion and thus making 2017 the slowest M&A year of the past five. These figures encompass global drug makers,” the analysis says. “Many blamed uncertainty over US tax reforms for holding big companies back from making bold strategic moves. Escalating valuations were another culprit, while the hobbling of several of the industry’s serial acquirers, namely the specialty companies, cannot have helped.
Helping propel a significant upswing in pharma/biotech M&A transactions so far in 2018 is the implementation of the new tax law, which cuts corporate tax rate from 35 percent to 21 percent and encourages companies to bring back huge cash held overseas at a one-time tax rate of 10 percent. As a result, big pharma and biotech companies based in the U.S. can more fairly compete with foreign counterparts firms that operate in better tax environments.
2018 opened with a surge in prime-time transactions during January as Sanofi acquired Ablynx and Bioverativ while Celgene landed Juno Therapeutics and Impact Biomedicines. On Jan. 22nd, Sanofi announced a deal representing an equity value of $11.6 billion (on a fully diluted basis) to acquire Bioverativ, a biopharmaceutical company focused on therapies for hemophilia and other rare blood disorders. The transaction, completed on March 8th, expands Sanofi’s presence in specialty care and strengthens the company’s leadership in rare diseases. The deal also provides Sanofi with a leader in the growing hemophilia market and provides a platform for expansion in other rare blood disorders.
One week after the announcement of the Bioverativ transaction, Sanofi agreed to purchase Ablynx at a price per share of €45 in cash for the biopharmaceutical company, representing an aggregate equity value of €3.9 billion. The deal, bolsters Sanofi’s R&D strategy with Ablynx’s innovative Nanobody technology platform. Nanobodies are proprietary therapeutic proteins based on single-domain antibody fragments, which combine the advantages of conventional antibody drugs with some features of small-molecule drugs. The acquisition also expands the French drugmaker’s growing rare blood disorders franchise with Ablynx’s late-stage investigational product caplacizumab for treating acquired thrombotic thrombocytopenic purpura (aTTP).
On Jan. 7th, Celgene revealed the signing of a definitive agreement to buy Impact Biomedicines, which has been developing the highly selective JAK2 kinase inhibitor fedratinib for myelofibrosis and polycythemia vera. Celgene made an up-front payment of $1.1 billion and is also responsible for $1.25 billion in contingent payments to Impact Biomedicines shareholders based on regulatory approval milestones for myelofibrosis. Additional future payments for regulatory approvals in other therapeutic indications and sales-based milestones are also possible. A New Drug Application filing for fedratinib in myelofibrosis was planned for mid-2018.
Celgene’s busy January continued when the Summit, N.J.-based biopharma company agreed to purchase Juno Therapeutics for $87 per share in cash – representing a total of $9 billion – net of cash and marketable securities acquired and Juno shares already owned by Celgene (9.7 percent of outstanding shares). Juno is regarded as a pioneer in the development of CAR (chimeric antigen receptor) T and TCR (T cell receptor) therapeutics with a broad, novel portfolio assessing multiple targets and cancer indications. Adding to Celgene’s lymphoma program, JCAR017 (lisocabtagene maraleucel; liso-cel) represents a potentially best-in-class CD19-directed CAR T undergoing a pivotal program for relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). U.S. regulatory approval for JCAR017 is on track for 2019 with potential worldwide peak sales of $3 billion.
February deals included Merck’s A$502 million ($394 million) agreement to purchase the Australian oncolytic immunotherapies manufacturer Viralytics. This move is intended to strengthen Merck’s presence in the fast-growing immuno-oncology market. The proposed acquisition of Viralytics adds the investigational oncolytic immunotherapy Cavatak, supporting Merck’s strategy to broaden its pipeline with the best scientific assets. According to Reuters, the deal came at a time of booming merger and acquisition activity in the biotechnology sector, with $27.5 billion of transactions agreed in January alone as large drugmakers continue to seek promising assets to improve their pipelines.
Roche Holding agreed to purchase the remainder of U.S. cancer data company Flatiron Health that it did not already own for $1.9 billion to speed development of cancer medicines and support the Swiss biotech company’s efforts to price them based on how well they work. Roche already owned 12.6 percent of Flatiron – a privately held company backed by Alphabet – that taps into data on individual cancer cases to help physicians chose promising approaches for their patients.
March merger and acquisition activity included the Danish drug company Lundbeck’s deal potentially worth $1.1 billion to purchase Prexton Therapeutics, a specialist in brain disorder treatments. Prexton’s drug candidate foliglurax is undergoing Phase II testing for the treatment of Parkinson’s disease, with first data expected to be available during first-half 2019.
A big deal was announced by Novartis during April when the Swiss company entered into an agreement to acquire AveXis for $8.7 billion. The acquisition of the U.S.-based clinical-stage gene therapy company was finalized on May 15th. AveXis’ lead product candidate, AVXS-101, has the potential to be first-ever one-time gene replacement therapy for spinal muscular atrophy (SMA), a disease that results in early death or lifelong disability with considerable healthcare costs. Granted breakthrough therapy designation by the FDA, AVXS-101 is expected to be launched in the United States during 2019 and represents multi-billion dollar peak sales potential. In addition, AveXis offers a valuable gene therapy platform, with potential beyond SMA, and scalable manufacturing to accelerate potential future gene therapy programs and launches for Novartis.
The largest industry deal of the year by far occurred during May with Takeda Pharmaceutical’s proposed 45.3 billion pound ($62 billion) acquisition of Shire. This transaction will create a global, values-based, R&D-driven biopharmaceutical leader with headquarters in Japan. The acquisition represents the largest overseas purchase by a Japanese company and will vault Takeda into one of the world’s top 10 global drug manufacturers.
The Takeda and Shire combination will unite complementary positions in gastroenterology and neuroscience, and provides leading positions in rare diseases and plasma-derived therapies to complement strength in oncology and focused efforts in vaccines. Expected to close during the first half of 2019, Takeda shareholders will own 50 percent of the combined group.
Eli Lilly announced a pair of acquisitions within five days of each other during May. First up was a $1.6 billion transaction reported on May 10th that strengthens Lilly’s clinical portfolio with ARMO BioSciences’ lead immuno-oncology asset and PEGylated IL-10 pegilodecakin, which is being studied in multiple tumor types. ARMO BioSciences is a late-stage immuno-oncology company that has been developing a pipeline of novel, proprietary product candidates designed to activate the immune system of cancer patients to recognize and eradicate tumors.
Lilly then expanded its oncology pipeline with the acquisition of AurKa Pharma. AurKa was established by TVM Capital Life Science to develop the oncology compound AK-01, an Aurora kinase A inhibitor that was originally discovered at Lilly. The compound represents a potential first-in-class asset that AurKa Pharma has been evaluating in Phase 1 studies in multiple types of solid tumors.
J&J’s Janssen Biotech announced during early May a definitive agreement to purchase BeneVir Biopharm, a privately held biopharmaceutical company specializing in the development of oncolytic immunotherapies. BeneVir uses a proprietary T-Stealth Oncolytic Virus Platform to engineer oncolytic viruses tailored to infect and destroy cancer cells. Including milestone payments, the reported $1+ billion deal was expected to close during the second quarter of 2018.
5 Biotech Stocks To Buy With Amazing Pipelines
1. Amgen Inc. (AMGN)
2. Seattle Genetics Inc. (SGEN)
3. Spectrum Pharmaceuticals Inc. (SPPI)
4. Gilead Sciences Inc. (GILD)
5. BioMarin Pharmaceutical Inc. (BMRN)
Source: InvestorPlace (March 27, 2018)
Top 5 Biotech Stocks For 2018
1. Celgene Corp. (CELG)
2. Gilead Sciences Inc. (GILD)
3. Exelixis Inc. (EXEL)
4. Enzo Biochem Inc. (ENZ)
5. AbbVie Inc. (ABBV)
Source: Investopedia (May 3, 2018)
U.S. biosimilar approvals are on the rise, including three in December 2017-May 2018 period
Zarxio (filgrastim-sndz) was the first biosimilar to gain Food and Drug Administration regulatory approval in March 2015. During 2016, three biosimilars were granted U.S. marketing clearance. Then in 2017, the amount of biosimilar approvals in the United States more than doubled from the previous two-year total of four, as five more were given the green light by FDA officials including two regulatory nods during December. Each of those five products that garnered FDA approval during 2017 were biosimilars of complex blockbuster therapeutic antibodies, two of which are in new therapeutic areas for biosimilars.
Then in May 2018, Pfizer’s anemia treatment Retacrit became the 10th biosimilar to win U.S. approval (see below for a listing). Retacrit represents the first biosimilar erythropoiesis-stimulating agent (ESA) to be approved in the United States. Retacrit marks Pfizer’s third approved biosimilar by the FDA.
U.S. APPROVED BIOSIMILARS AS OF MAY 2018
Biosimilar Applicant Reference Drug Approval Date
Zarxio (filgrastim-sndz) Sandoz Neupogen March 2015
Inflectra (infliximab-dyyb) Celltrion and Hospira* (*now part of Pfizer) Remicade April 2016
Erelzi (etanercept-szzs) Sandoz Enbrel August 2016
Amjevita (adalimumab-atto) Amgen Humira September 2016
Renflexis (infliximab-abda) Samsung Bioepis Remicade May 2017
Cyltezo (adalimumab-adbm) Boehringer Ingelheim Humira August 2017
Mvasi (bevacizumab-awwb) Amgen and Allergan Avastin September 2017
Ogivri (trastuzumab-dkst) Mylan and Biocon Herceptin December 2017
Ixifi (infliximab-qbtx) Pfizer Remicade December 2017
Retacrit (epoetin alfa-epbx) Pfizer Epogen and Procrit May 2018
Sources: FDA and Med Ad News
IQVIA Institute for Human Data Science Study: Spending on Cancer Meds in the U.S. Doubled from 2012-2017 – Expected to Double Again by 2022 to $100 Billion
Biotechnology continues to play an essential role in the research and development of cancer medicines. The IQVIA Institute for Human Data Science issued a report during May called “Global Oncology Trends 2018: Innovation, Expansion and Disruption.
The report notes that spending on cancer drugs in the United States doubled since 2012 to reaching almost $50 billion in 2017, with two-thirds of the growth tied to medicines launched within the past five years. Those product costs are expected to double again by 2022. Outside the United States, oncology drug costs exceeded $60 billion during 2017, driven by new product launches and increased use of existing brands.
• Despite growing costs to payers, the average patient with commercial insurance paid less than $500 per year for outpatient non-retail medicines in 2017
• For retail medicines, patients frequently use coupons to reduce out-of-pocket cost at pharmacies
• All oncology medicines launched in 2017 carried list prices above $100,000 per year in the United States
• The top 35 cancer drugs account for 80 percent of total worldwide cancer spending
• More than 700 cancer drugs are in late-stage development – up more than 60 percent from one decade ago
• The global cancer drug market will reach $200 billion by 2022, averaging 10-13 percent annual growth, while the U.S. market is projected to increase 12-15 percent annually during the same period
The study demonstrated wide differences in final out-of-pocket costs for U.S. patients paying for cancer medicines based on drug choice, manufacturer prices and insurance plans. While outpatient drugs often lead to high costs for payers, the patient responsibility averages less than $500 per year for commercial plans and patient costs for retail drugs are often reduced by extensive use of coupons, which offsets high-cost exposure.
“Payers continue to be challenged as they seek value and fund access to the latest oncologic treatment options,” explains Murray Aitken, IQVIA senior VP and executive director of the IQVIA Institute for Human Data Science.
“The surge in innovation brings new dimensions of complexity, even as the availability of predictive biomarkers and diagnostic tests can help bring a more precise course of treatment to an individual patient,” Aitken notes. “There are also a number of disruptive technologies that will reshape healthcare and cancer specifically, including data science that incorporates artificial intelligence and real-world data, as well as advances in patient engagement through mobile apps.”
Among other highlights within the full Global Oncology Trends 2018 report (available at www.IQVIAInstitute.org, including a detailed description of the study methodology):
Advances in Cancer Therapeutics: 14 new cancer therapeutics were launched during 2017, each of them targeted therapies with 11 receiving “Breakthrough Therapy” status from the FDA – showing substantial improvement over existing therapies on one or more clinically significant endpoints. Since 2012, 78 approved therapies have been launched – relating to 24 different tumor types – with some treating multiple tumor types. In 2017, PD-1 and PD-L1 inhibitors were used to treat patients with 23 different tumor types, of which the primary use was lung cancer. The new medicines launched during last year represented significant clinical advances and contributed to patients’ overall survival across a range of tumors and mechanisms.
Use and Spending Levels for Cancer Treatments: Global spending on cancer medicines – for therapeutic and supportive care – increased to $133 billion globally in 2017, up from $96 billion during 2013. Spending on cancer medicines is heavily concentrated among the top 35 drugs, which represent 80 percent of total spending. List prices of new cancer drugs at launch have grown steadily during the past decade, and in the United States the median annual cost of a cancer drug launched in 2017 exceeded $150,000, compared to $75,000 for new cancer treatments introduced to the market 10 years ago. Most cancer medicines – including those with high annual costs – are used by relatively few patients. An estimated 87 percent of oncology products were used by fewer than 10,000 patients during 2017.
Pipeline of Therapeutic Innovation: The industry’s pipeline reached a historic level of more than 700 molecules in late-stage development during 2017, up more than 60 percent from a decade ago. Clinical trials using biomarkers to stratify patients susceptible to response made up 34 percent of oncology studies in 2017. The pipeline of immunotherapies is particularly active and includes almost 300 molecules with 60 separate mechanisms being studied in Phase I or Phase II clinical trials. These products are being tested against 27 different tumor types, indicating the broad-based application of this new approach to cancer treatment. While many efforts seek to shorten the “molecule-to-market” timeline, new drug approvals during 2017 had a median time span of 14 years from patent filing, only slightly faster than 2013.
Outlook for Oncology Through 2022: Advances in technology and the use of information will be driving forces that affect oncology treatment and costs during the next decade. Of particular note, mobile cancer apps are being used – albeit in small numbers – across the patient journey, from prevention to survivor support. Apps are additionally being incorporated into clinical studies as an adjunct to other interventions or for validation. In fact, in 2017 there were 15 published studies that found positive impacts of cancer apps across a range of uses. The worldwide market for oncology therapeutic medicines is predicted to reach $200 billion by 2022, averaging 10-13 percent growth during that time, while the U.S. market is projected to reach $100 billion with an average growth rate of 12-15 percent during the same period.
Global Biologics Market to Surpass $300 Billion by 2022 with Accelerated New Launches in Oncology
According to Frost & Sullivan analysis, “Global Biologics Market-Companies-to-Action,” leading pharmaceutical companies such as Roche, Amgen, Sanofi, AbbVie, Novo Nordisk and others are increasingly focusing on biologics due to a growing demand for innovative therapies and rising patent cliffs. Frost & Sullivan experts expect cell and gene therapy to show strong potential, especially across the rare diseases segment. Pharmaceutical companies including Amgen, Sanofi, and Pfizer are investing in molecules in the early stages of clinical development in this therapy. If approved, these molecules have the potential to propel the regenerative medicine market by almost seven percent, exceeding the $10 billion barrier.
The Frost & Sullivan study (for further information on the analysis, please visit: http://frost.ly/286) predicts that the market will reach more than $300 billion by 2022 at a compound annual growth rate of nearly 10 percent.
“To keep up with the growing demand for new and advanced therapies, companies are either adopting hybrid business models or indulging in partnerships or acquisition activities to attain technology proficiency as well as specific therapy expertise,” notes Aarti Chitale, Transformational Health Senior Research Analyst at Frost & Sullivan. “As a result, virtual pharmaceutical companies are coming to the fore by collaborating with bigger pharmaceutical players and providing specific services to these partners in terms of drug discovery, development, or manufacturing.”
Per the analysis, strategic imperatives for the global biologics companies include:
• Concentrating on unmet needs by investing across the most promising segments, including oncology, neurological disorders, infectious diseases, diabetes, and immunology among others, which have shown high acceptability across regions;
• Capturing investment opportunities through partnerships with niche players;
• Forming strategic collaborations: Small-to-mid sized pharma companies are focusing on biologics discovery and development, by collaborating with larger pharmaceutical and generic manufacturers, contract development and manufacturing organizations (CDMOs) and Contract Research Organizations (CROs); and
• Adopting newer development and manufacturing techniques, such as improvements in bioanalytical testing.
“Alongside industry and academic research collaborations, companies are focusing on partnering with IT players such as IBM Watson Health and GE Healthcare Life Sciences, which provide technologically advanced solutions for conducting clinical trials and supporting complex drug manufacturing processes,” Chitale explains. “While these collaborations are expected to mitigate certain manufacturing difficulties and create integrated business models, higher manufacturing costs are likely to affect the pricing of these molecules, thus impacting the adoption rate, especially across emerging markets with inadequate reimbursement facilities.”
“Disruptive Innovators: CRISPR, CART T-cell therapies, and the value of new science”
ISPOR, the professional society for health economics and outcomes research, released a report titled “ISPOR 2018 Top 10 HEOR Trends.” The report reveals the top trends in health economics and outcomes research that will likely have the most impact on healthcare in 2018 and beyond.
According to ISPOR, interest in the field of health economics and outcomes research (HEOR) has grown exponentially as governments and other payers grapple with how to provide the best possible health outcomes at affordable costs. As HEOR continues to play an ever-greater role in helping to inform healthcare decisions, the society has developed its first compilation of the top trends that ISPOR members have identified as having the most influence over during 2018.
One of the 10 trends identified in the report is “Disruptive Innovators: CRISPR, CART T-cell therapies, and the value of new science.” Following is that trend’s excerpt from the report (https://www.ispor.org/top10trends.pdf).
This is not your parents’ biotechnology. During the past decade, scientific innovations in cell and gene research have been creating new therapies that will make monoclonal antibodies look as sophisticated and efficient as early generation small molecule drugs. They are tremendously exciting in the scientific and medical sense and pose some new challenges to those involved in health technology assessment and healthcare decision making.
One of the techniques – promising as well as controversial – is CRISPR. The acronym, which stands for clustered regularly interspaced short palindromic repeats, is a genome-editing technology. CRISPR offers tremendous potential to produce therapies that can edit disease-causing genetic mutations. Another innovative technology is the class of immunotherapies known as CART T-cell therapies. CART T-cell therapies are a type of adoptive cell transfer in which patients’ own immune cells are collected and used to treat their cancer.
Products created by techniques such as CRISPR and CART-T bring value to healthcare in two ways. First, they create immediate benefits for those patients who are treated for the initial indications of these products; these benefits are routinely accounted for in health economic evaluation. Secondly, they create “scientific spillovers” (ie, new scientific knowledge that can be applied to development of other new therapies), the commercial benefits of which often cannot be fully realized by those creating these spillovers, despite patents and other intellectual property protections.23
In an economic sense, it is important not to under-reward these fundamental advances in order to maintain the research incentives for such important breakthroughs. Not all incentives are monetary, to be certain, and it is expected that society at large will realize much of the benefit of new therapies. The value of scientific spillovers is typically not captured in economic evaluations of new products, creating concerns that non-commercial incentives (such as government funding of research) may not be sufficient to encourage these key advances. However, this value is not straightforward to measure, particularly for disruptive therapies because all of their applications may not be immediately foreseen. Group-based deliberative processes, such as multiple criteria decision analysis,24 are being considered increasingly as a way to make decisions about new technologies, especially when their costs and/or benefits extend beyond those that are well-measured by standard economic evaluation.
23. Garrison LP, Kamal-Bahl S, Towse A. Toward a broader concept of value: identifying and defining elements for an expanded cost-effectiveness analysis. Value Health. 2017; 20(2): 213-216.
24. Thokala P, Devlin N, Marsh K, et al. Multiple Criteria Decision Analysis for Health Care Decision Making – An Introduction: Report 1 of the ISPOR MCDA Emerging Good Practices Task Force. Value Health. 2016;19(1):1–13
“GlobalData Healthcare 2017 Biopharmaceutical Industry R&D Review”
For the biopharmaceutical industry, 2017 was marked by noteworthy innovation as well as disappointments across therapy areas, set against a backdrop of remarkable advances in technology in healthcare and the growing presence of biosimilars according to analysis from GlobalData, a leading data and analytics company.
GlobalData reviewed industry R&D activity in 2017 under four key headings: Clinical Breakthroughs, R&D Disappointments, Digital Health Advances, and Growing Biosimilar.
During the course of 2017, regulatory approvals of first-in-class and otherwise groundbreaking novel drugs occurred in nearly every major therapeutic area.
• The first two CAR T-cell drugs in oncology, Novartis’ Kymriah in acute lymphoblastic leukemia (ALL) and Gilead’s Yescarta in diffuse large B-cell lymphoma (DLBCL)
• The first biologic in atopic dermatitis, Regeneron’s Dupixent
• The first drug indicated for primary progressive multiple sclerosis, Roche’s Ocrevus
Claire Herman, Global Director of Therapy Analysis and Epidemiology at GlobalData, states, ‘‘Each of these approvals fills a critical clinical unmet need and alters the treatment paradigm.’’
Pharmaceutical R&D experienced significant setbacks during 2017. The historically high attrition rate in Alzheimer’s disease therapeutics persisted, with the failures of two high-profile 5-HT6 receptor antagonists, according to the analysis. In the rapidly expanding immuno-oncology space, the blockbuster products Keytruda and Opdivo failed to meet endpoints in key trials in head & neck cancer and glioblastoma, respectively.
However, as Herman notes, ‘‘In Alzheimer’s, oncology, and other areas that saw late-stage failures in 2017, other candidates are waiting in the wings.’’
Digital Health Advances
The impact of technology on healthcare was felt far and wide throughout 2017. During the year, the industry saw advances in digital health across the spectrum of the drug lifecycle, from clinical trials, to disease diagnosis, to treatment selection, to patient monitoring.
Herman says, ‘‘With collaborations between pharma companies and technology giants such as Apple and Google making headlines regularly, the pace of digital health innovation is unlikely to slow in the year to come.’’
In oncology and immunology, biosimilars are becoming an increasingly competitive therapeutic choice, and ophthalmology is not far behind, per GlobalData. The approvals in 2017 and previous years of lower-priced biosimilar versions of market-leading branded biologics – including top-sellers Humira, Remicade, Enbrel, Herceptin, and Rituxan – have not led to high uptake in the clinic. However, as Herman explains, ‘‘As physicians’ comfort with the class grows, we expect increased erosion in 2018 and beyond.’’
Widespread Underuse of Specimens Concerns Biobanks, Says Landmark Survey
iSpecimen released during May the company’ newest biobanking survey report covering data and trends in the biobanking industry. According to the study, a majority of global biobanks – collectors of human fluids, cells and tissue for biomedical research – are underutilizing their specimens while struggling with financial pressures that threaten their long-term viability. Other data points from the report (located at pages.ispecimen.com/Worldwide-Biobanking-Survey-Download.html) include:
• Sixty-seven (67) percent of the participating biobank respondents cited underutilization of samples as a major or moderate biobank challenge.
• More than half of respondents said they collect more samples than they release to researchers.
• 64 percent of respondents cited economic sustainability as a major or moderate biobank challenge.
• Only 44 percent of respondents release specimens to external researchers from for-profit organizations with whom they are collaborating and only 24 percent of respondents said specimens are related to specimen brokers or commercial biorepositories.
“These findings are important,” states iSpecimen Founder and CEO Christopher Ianelli, MD, PhD. “We already know that researchers struggle to obtain the samples they need for their important research. Our review confirms that there’s a pent-up supply of biospecimens in storage, and that biobanks want to do something about it. Broader sample sharing would address both the underutilization and specimen availability problems, as well as the challenge of economic sustainability.”