R&D success and M&A activity loom as large swing factors for the bio sector in 2017 with the regulatory arena potentially at its most amenable for years.


After a down year in terms of the amount of FDA approvals for new medicines and therapeutic biological products in 2016, the first five months of 2017 were a different story. As of May 22, 2017, the U.S. Food and Drug Administration had approved for marketing 21 new molecular entities and novel biologics license applications this year compared to 22 for the entirety of 2016. In comparison, there were 41 NME/BLA approvals during full-year 2014 and 45 novel drug approvals throughout 2015.

As various reports have detailed, FDA’s 2016 new drug approval amount decline can be partly attributed to several new medicines being cleared for marketing before year-end 2015 while some other regulatory approval decisions were pushed back from 2016 into 2017.

QuintilesIMS data shows that the current state of the pharma industry’s late-phase R&D pipeline is in a good position to produce an average of 40 to 45 new launches per year through 2021.

According to EvaluatePharma analysis, the projected amount of new medicine launches during 2017 consists of no less than 15 blockbusters by 2022, along with three other drugs that are forecast to reach nearly $1 billion in annual sales by that year.

Leading the 2017 new drug approval cavalry charge are a number of biotech and biopharma medicines that have industry analysts excited about their mega-sales potential. Projected future blockbuster brands that have already emerged in the U.S. marketplace this year include: the Roche/Genentech multiple sclerosis treatment Ocrevus (ocrelizumab); the eczema drug Dupixent (dupilumab) and the rheumatoid arthritis medicine Kevzara (sarilumab) from the Sanofi and Regeneron Pharmaceuticals partnership; AstraZeneca/MedImmune’s immunotherapy Imfinzi (durvalumab) for bladder cancer; Tesaro’s Zejula (niraparib) for maintenance treatment of recurrent ovarian cancer; and Novartis’ Kisqali (ribociclib) for metastatic breast cancer. All of these new products are projected to generate peak annual sales of at least $2 billion and some may exceed the $5 billion barrier at their apex. For more details on these products, please see the “Recent FDA Drug Approvals with Significant Market Impact” section below.

Other projected future blockbuster brands that are on track to gain FDA regulatory clearance by year-end 2017 include Novo Nordisk’s diabetes drug semaglutide, Kite Pharma’s axicabtagene ciloleucel for rare forms of blood cancer, and Johnson & Johnson’s apalutamide for prostate cancer.

Semaglutide is a once-weekly analog of human glucagon-like peptide-1 (GLP-1) that stimulates insulin and suppresses glucagon secretion in a glucose-dependent manner, while also decreasing appetite and food intake. The new product candidate is undergoing regulatory review in the United States, European Union, and Japan.

Axicabtagene ciloleucel is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. In late May, the FDA accepted for priority review the BLA for axicabtagene ciloleucel for patients with refractory aggressive non-Hodgkin lymphoma (NHL). Additionally, Kite’s lead drug candidate has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the FDA and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

Also known by the product code ARN-509, apalutamide is undergoing U.S. and EU Phase III development as monotherapy for pre-metastatic castration-resistant prostate cancer, metastatic hormone sensitive prostate cancer, and localized prostate cancer.

Vigorous Growth for New Biotech Products

According to a recently completed assessment from the Tufts Center for the Study of Drug Development, biopharmaceuticals represented 35 percent of all new drug approvals in the United States from 2006 through 2016. Per the assessment, a robust development pipeline suggests that the recent increased pace of biotech approvals will continue for the next decade.

The annual rate of 13 new biotech products approvals by the U.S. FDA during the study period accelerated to more than 20 per year during 2014-2016, Tufts CSDD found. Also, 220 major pharmaceutical and biotechnology firms worldwide were conducting 429 Phase III clinical trials for biopharmaceuticals at year-end 2016.

“Given the historically high, 74 percent Phase III-to-approval success rate of biologicals in late-stage development, and the extensive biotech product pipeline, the high pace of biotech product approvals will likely continue through the next decade,” commented Ronald Evens, PharmD, FCCP, adjunct research professor at Tufts CSDD, who performed the analysis.

According to Evens, the relative advantages of biotech product development over small-molecule drugs – higher approval numbers and success rates, more first-in-class products with high impact on disease mitigation and cures, and a high likelihood of obtaining favorable reimbursement – will help maintain the current pace of U.S. biotechnology approvals.

Among the key findings from the analysis, issued in the May/June Tufts CSDD Impact Report:

• FDA approved 225 new biotech products during 2000-2016, versus 304 small-molecule drug approvals within the same time frame.

• Biotech products in Phase III clinical studies spanned an extensive range of molecules, with monoclonal antibodies accounting for 34.5 percent of the total.

• Biotech products spanned a wide array of disease areas in Phase III trials at the end of 2016, with one-third concentrated on oncology.

• Biosimilars represented more than 60 products in Phase III trials during 2016.

“By any measure, the biotechnology revolution has had a significant impact – by fostering development of life-saving and life-extending treatments and promoting dramatic growth in the biotech sector, which promises still more product innovation,” Evens noted.

The Tufts Center for the Study of Drug Development at Tufts University provides strategic info to help drug developers, regulators, and policy makers improve the quality and efficiency of pharmaceutical development, review, and utilization.


Recent FDA Drug Approvals with Significant Market Impact

In the first half of 2017, various new medicines with blockbuster sales potential have garnered regulatory marketing clearance from the U.S. FDA. Following is a look at some of the new biotech/biopharma products to enter the U.S. marketplace in 2017 along with other already-approved drugs that recently were approved for new indications that will help bolster their already-potent sales potential.

Ocrevus (ocrelizumab)

Roche won U.S. marketing approval in late March for a potential mega-blockbuster brand that targets severe form of multiple sclerosis. Ocrevus was FDA-approved as the first medicine for both relapsing and primary progressive forms of multiple sclerosis. The majority of individuals with multiple sclerosis have a relapsing form or primary progressive MS at diagnosis.

The humanized monoclonal antibody is designed to selectively target CD20-positive B cells, a specific type of immune cell believed to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can result in disability in people with multiple sclerosis. Based on preclinical studies, Ocrevus binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore significant functions of the immune system may be preserved.

Ocrevus represents a significant new treatment option for people with relapsing forms of MS (RMS) demonstrating superior efficacy on the three major markers of disease activity compared with Merck KGaA/EMD Serono’s Rebif (high-dose interferon beta-1a). The Roche product is administered by intravenous infusion every six months. A list price of $65,000 per year reportedly undercuts rival Rebif by a quarter.

Industry analysts project yearly sales exceeding $3 billion by 2021, according to Reuters data. According to EvaluatePharma January 2017 data, Ocrevus is forecast to generate $4 billion in global sales during 2022. The MS treatment rated as the most valuable R&D drug per EvaluatePharma as of April 2017 with a net present value (NPV) of $18.3 billion.

Dupixent (dupilumab)

A recent FDA drug approval to emerge from the Sanofi-Regeneron partnership is Dupixent Injection. In March, the product received U.S. regulatory approval for treating adults with moderate-to-severe atopic dermatitis. Dupilumab is an antibody that blocks signaling of IL-4 and IL-13.

The launch of Dupixent commenced following the March 28 FDA approval for treating adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupixent has a list price of $37,000 per year.

Dupilumab is being studied in asthma, in children with atopic dermatitis, in nasal polyps, and in eosinophilic esophagitis. During first-quarter 2017, a Phase III trial of Dupixent in adolescent patients (12-17 years of age) with moderate-to-severe atopic dermatitis was initiated. In second-quarter 2017, a Phase III trial of dupilumab in pediatric patients (6-11 years of age) with uncontrolled persistent asthma began.

Wall Street analysts forecast annual sales exceeding $4 billion by 2022 for the injectable biotech drug, according to Thomson Reuters data. EvaluatePharma ranked Dupixent as the second-highest most valuable R&D drug with an NPV of $15.8 billion, with a 2022 sales projection of $4.6 billion.

Imfinzi (durvalumab)

AstraZeneca and its global R&D arm MedImmune in May received the first marketing approval worldwide for the immunotherapy Imfinzi (durvalumab) as a treatment for bladder cancer. FDA granted accelerated approval to Imfinzi for treating patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemo before (neoadjuvant) or after (adjuvant) surgery.

Imfinzi is a human monoclonal antibody that blocks programmed death-ligand 1, which blocks the interaction of PD-L1 with its immunoinhibitory receptor PD-1 and CD80. PD-L1 is a 40kDa type 1 transmembrane protein that is believed to play a major role in suppressing the immune system during particular events including pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis.

Durvalumab is additionally being studied in the first-line treatment of patients with unresectable and metastatic bladder cancer as a monotherapy and in combination with tremelimumab – a checkpoint inhibitor that targets CTLA-4 – as part of the DANUBE Phase III trial, of which the last patient commenced dosing in first-quarter 2017 (worldwide trial, excluding China). Additional clinical studies are under way to investigate durvalumab as monotherapy or in combination in multiple solid tumors and blood cancers.

“We are excited to offer Imfinzi as a breakthrough therapy for patients with locally advanced or metastatic bladder cancer,” noted Pascal Soriot, AstraZeneca’s CEO. “Imfinzi is the cornerstone of our extensive Immuno-Oncology program, in development across many tumor types, as monotherapy and in combination. This first approval for Imfinzi is an important milestone in our return to growth and brings us another step closer to our goal of redefining the way cancer is treated.”

Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumors. According to AstraZeneca and MedImmune, their IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumor immune suppression. Company management believes that IO-based therapies will offer the potential for life-changing cancer treatments for the vast majority of patients.

The average wholesale acquisition cost of Imfinzi totals about $15,000 a month. According to EvaluatePharma’s Top 10 Most Valuable R&D Drugs listing in April, durvalumab ranked No. 3 with a net present value of $12.8 billion. According to that company’s January report, durvalumab is on track to generate sales of $2.3 billion in 2022.

Zejula (niraparib)

With FDA approval in March 2017, Zejula became the first poly(ADP-ribose) polymerase (PARP) inhibitor to be cleared for marketing for the maintenance treatment of women with recurrent ovarian cancer. Zejula is indicated for the maintenance treatment of women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response (CR or PR) to platinum-based chemotherapy. Zejula is the first PARP inhibitor to gain FDA approval that does not require BRCA mutation or other biomarker testing.

Containing the active chemical niraparib, the drug was commercially launched in the United States during April by the oncology-focused biopharma company Tesaro. The product’s wholesale acquisition cost is $9,833 for a one-month supply at a dose of 200 milligrams once daily. Zejula awaits EU marketing approval since being submitted for EMA review in October 2016. Per EvaluatePharma January 2017 analysis, Zejula annual global sales are forecast to hit the $1.8 billion mark in 2022.

Kisqali (ribociclib)

The FDA in March approved Kisqali in combination with any aromatase inhibitor as initial endocrine-based therapy for treating postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative advanced or metastatic breast cancer. The drug was reviewed and approved via FDA’s Breakthrough Therapy designation and Priority Review programs.

Kisqali belongs to a class of drugs known as selective cyclin-dependent kinase inhibitors that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can allow cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate at an uncontrollable rate.

According to an EvaluatePharma January report, Kisqali is forecast to produce global sales of $1.5 billion in 2022.

Kevzara (sarilumab)

Sanofi and Regeneron in May received another FDA approval: for Kevzara as a treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX). A human monoclonal antibody, Kevzara binds to the interleukin-6 receptor (IL-6R) and has been demonstrated to inhibit IL-6R mediated signaling. IL-6 is a cytokine in the body that, in excess and over time, can contribute to inflammation associated with RA.

The U.S. wholesale acquisition cost (WAC) of Kevzara is $39,000 annually for the 200 mg and 150 mg doses, which is 30 percent lower than the WAC for the two most widely used TNF-alpha inhibitors. Actual costs to patients, payers and health systems are expected to be lower as WAC does not reflect discounts, rebates or copay support according to the companies.

Kevzara will be marketed in the United States by Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi. The new medicine was approved in Canada during January 2017. Three months later, the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the marketing authorization of Kevzara recommending its approval for use in adult patients with moderately to severely active RA. The companies are additionally seeking approvals in various other countries around the world.

According to some analysts’ projections, Kevzara is projected to generate about $557 million in yearly revenue by 2022.

Keytruda (pembrolizumab)

In October 2016, Merck & Co.’s Keytruda was granted accelerated approval by the FDA (seven weeks after accepting the application) as the first drug in its anti-PD-1 therapy class to reach the front line in lung cancer. With this new indication, Key­truda became a first treatment option instead of chemotherapy for patients with metastatic non-small cell lung cancer whose tumors express high levels of PD-L1 (programmed death receptor-1).

Another first was achieved by Keytruda in May 2017: the medicine became the first cancer therapy approved for use based on a biomarker, regardless of tumor type. Granted accelerated approval, Keytruda received this first-of-its-kind indication: the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high or mismatch repair deficient, solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

“This is the first time in the history of oncology that a cancer medicine has been approved by the FDA using a pan-tumor predictive biomarker rather than a tumor-specific approach,” noted Dr. Luis A. Diaz Jr., head of the Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center. “This approval for Keytruda is a transformational milestone in our progress toward personalized immunotherapy, offering certain patients with difficult-to-treat cancers a medicine based on the genetic makeup of the tumor – regardless of tumor type.”

The human programmed death receptor-1 (PD-1)-blocking antibody was initially approved by U.S. regulators in September 2014 for treating patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

A humanized monoclonal antibody, Keytruda works by increasing the ability of the body’s immune system to help detect and fight tumor cells. The product blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes that may affect tumor cells and healthy cells.

According to EvaluatePharma April 2017 analysis, Keytruda is projected to rank as the third-best-selling prescription medicine worldwide in 2022 with global sales of $12.04 billion. The product’s 2016 sales for Merck totaled more than $1.4 billion.

Opdivo (nivolumab)

According to EvaluatePharma analysis, trailing behind Keytruda as the No. 4 best seller during 2022 is expected to be Opdivo. Having generated 2016 sales of more than $3.77 billion for Bristol-Myers Squibb, helping the medicine’s prospects of generating higher annual sales in the years to come is another FDA indication that was approved in February 2017. Opdivo injection received accelerated marketing clearance for intravenous use for treating patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. With that FDA approval, Opdivo has been approved in six tumor types in just more than two years.

Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world during July 2014. Opdivo is approved for marketing in more than 60 countries, including the United States, the European Union and Japan. During October 2015, Bristol-Myers Squibb’s Opdivo and Yervoy combination regimen was the first immuno-oncology combination to receive regulatory clearance for treating metastatic melanoma and is approved in 50-plus countries, including the United States and European Union.

Opdivo is a PD-1 immune checkpoint inhibitor designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, the product has become a significant treatment option across multiple cancers.

Bristol-Myers Squibb’s worldwide development program founded on scientific expertise in the area of immuno-oncology includes a wide array of clinical trials studying Opdivo across all phases, including Phase III, in various tumor types. The Opdivo clinical development program had enrolled more than 25,000 patients as of May 2017.

Kalydeco (ivacaftor)

Another FDA approval in May came in the form of a new indication for Kalydeco: for use in people with cystic fibrosis (CF) ages 2 and older who have one of 23 residual function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. According to marketer Vertex Pharmaceuticals, this precision medicine decision was based on analyses of in vitro data and is supported by more than five years of real-world clinical data that demonstrate the drug’s strong safety and efficacy profile. The approval triples the amount of rare gene mutations that the drug can now treat, expanding the indication from the treatment of 10 mutations to 33.

In addition to the mutations added to the label based on the May 2017 approval, Vertex is continuing discussions with U.S. regulators regarding the approval for additional people who have mutations responsive to Kalydeco, including one of five “splice” mutations. These five mutations were studied as part of the previously disclosed Phase III EXPAND trial in which the Kalydeco monotherapy arm met its primary efficacy endpoint while being generally well tolerated.

In January 2012, Kalydeco became the first medicine to treat the underlying cause of cystic fibrosis. That FDA approval was received three months after the filing of the New Drug Application.

Based on the May 2017 approval, Vertex increased its Kalydeco guidance product revenue to a range of $740 million to $770 million for full-year 2017.

Actemra (tocilizumab)

Actemra received marketing clearance in May for a new indication: to treat adults with giant cell arteritis. With this approval, Roche/Genentech’s Actemra becomes the first FDA-approved therapy specific to this type of vasculitis. FDA granted this application via a Breakthrough Therapy designation and Priority Review.

Giant cell arteritis is a type of vasculitis, a group of disorders that leads to inflammation of blood vessels. Because of this inflammation, the arteries narrow or become irregular, impeding adequate blood flow. In giant cell arteritis, the vessels most involved are those of the head, particularly the temporal arteries (located on each side of the head).

Subcutaneous Actemra was previously FDA-approved for treating moderate to severely active rheumatoid arthritis. Intravenous Actemra was additionally already approved for treating moderate to severely active rheumatoid arthritis, systemic juvenile idiopathic arthritis and polyarticular juvenile idiopathic arthritis. Intravenous administration is not approved for giant cell arteritis.


Big Bio Deals

Pharma and biotech M&A activity in 2016 was down compared to the amount of deals during 2014 and 2015, particularly in the fourth quarter of last year.

“Activity in the fourth quarter was deeply suppressed by the run-up to the U.S. presidential election, especially as key issues – drug pricing, health insurance coverage and corporate tax reform – hung on the outcome,” according to EvaluatePharma analysis. “It could be no coincidence that to find a three-month period with less activity you have to go back to the last U.S. presidential election at the end of 2012.”

According to the analysis, the $98.7 billion spent on acquisitions during 2016 was less than half that of the biotech boom’s peak in 2014 even though many biotechnology targets became more affordable as their valuations tumbled through the course of last year. “Before the boom, $98.7 billion would have been seen as a good year, particularly as 2016 only featured one megamerger, the acquisition of Baxter’s Baxalta spinoff by Shire. The boom years were marked by multiple megamergers each year, three in 2014 and two in 2015,” according to EvaluatePharma.

The largest M&A transaction in the biotech community during 2016 was Shire’s $32 billion cash and stock acquisition of Baxalta. As a result of Shire’s six-month pursuit of Baxalta, the combination of the two companies created the world’s largest rare-disease drug manufacturer. Shares for both companies were down upon news of the announcement.

Baxalta, which was spun off from Baxter International during 2015, had previously rejected Shire’s earlier $30 billion all-stock offer. Shire initially offered only stock because of concerns of that inclusion of cash might put at risk the tax-free status of Baxalta’s spin-off from Baxter.

The combination of Shire and Baxalta established the leading global biotech company concentrated on serving patients with rare diseases and other highly specialized conditions. Baxalta’s target areas included rare blood conditions, oncology and immune system disorders. Through the combination, Shire anticipated producing double-digit compound annual top-line growth, with more than $20 billion in yearly projected revenue by 2020 and 65 percent of total revenue being accounted for by rare disease products. As a result of the transaction, Shire has more than 50 programs in clinical development, with a balanced mix of early, mid and late-stage projects.

The value of the Shire and Baxalta combination more than doubled that of the second-largest pharma and biotech M&A deal announced in 2016: Pfizer’s $14 billion acquisition of Medivation. The companies initiated joint operations on Sept. 28, 2016, with their combined expertise accelerating Pfizer’s leadership in oncology.

Now a wholly owned subsidiary of Pfizer, the biopharma company Medivation has been concentrating on developing and commercializing small molecules for oncology. Medivation’s product portfolio included Xtandi (enzalutamide), an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within the tumor cell. At the time of the acquisition, Xtandi was the leading novel hormone therapy in the United States with global annual sales of more than $2 billion. Medivation’s promising, late-stage oncology pipeline included two development-stage oncology assets, talazoparib and pidilizumab.

2017 started with a big-time pact as J&J announced in January its acquisition of Europe’s largest biotech company, Actelion. J&J launched an all-cash tender offer in Switzerland to acquire all of the outstanding shares of Actelion for $280 per share, payable in U.S. dollars. If seen to completion as anticipated during second-quarter 2017, the $30 billion transaction would rank as the eighth-largest M&A deal in the pharma/biotech sector during the past 10 years.

Actelion has established a leading franchise of differentiated, innovative medicines for pulmonary arterial hypertension (PAH) that is highly complementary to the existing portfolio of the Janssen Pharmaceutical Companies of J&J. The Actelion portfolio includes specialty in-market medicines and late-stage products. J&J expects to retain Actelion’s presence in Switzerland and leverage its complementary capabilities in shaping medical paradigms.

Immediately before the completion of the acquisition, Actelion will spin out its drug discovery operations and early-stage clinical development assets into a newly created Swiss biopharma company known as “R&D NewCo.” The shares of R&D NewCo will be distributed to Actelion’s shareholders as a stock dividend upon closing of the tender. J&J will initially hold 16% of the shares of R&D NewCo and have rights to another 16 percent of R&D NewCo equity via a convertible note. The arrangements will result in R&D NewCo launching with cash of CHF 1 billion to be available at the closing of the transactions. J&J will additionally receive an option on ACT-132577, a product within R&D NewCo being developed for resistant hypertension in Phase II clinical development.

Upon announcing its first-quarter 2017 results, including Actelion, J&J forecast 2017 sales of $75.4 billion to $76.1 billion and adjusted earnings of $7.00 to $7.15 per share. Management projected that Actelion will contribute 35-40 cents to earnings per share in 2018.


On The Biosimilars Front

According to a visiongain Ltd. February 2017 report (“Global Biosimilars and Follow-On Biologics Market 2017-2027”), the worldwide biosimilars and follow-on biologics market is expected to increase at a CAGR of 38.8 percent during the first half of the forecast period and CAGR of 11.3 percent in the second half of the projected period. The market is estimated at $5.31 billion in 2016 and $41.07 billion for 2027.

Helping pace the compound annual growth rate increase is the monoclonal antibodies (mAbs) segment. In a visiongain report issued in May 2017 (“Global Biosimilar Monoclonal Antibodies Forecast 2017-2027), the global biosimilar monoclonal antibodies market is projected to grow at a CAGR of 9.6 percent in the second half. The market, which is expected to increase at a CAGR of 23.8 percent from 2015 through 2027, is projected at $4.2 billion in 2020 and $7.9 billion during 2027.

Another biosimilar growth driver segment is the erythropoietin class. Blockbuster erythropoietin products during 2016 included Amgen’s Aranesp and Epogen as well as Johnson & Johnson’s Procrit. The CAGR for these products and some other erythropoietins based on annual worldwide sales is expected to decline between 2016 and 2022.

According to EvaluatePharma analysis, Epogen sales will halve by 2022. Aranesp is projected to recover lost Epogen sales and be the No. 1 seller by 2022, but its growth additionally is decreasing. As the threat from biosimilar competition intensifies sales will come under renewed pressure, EvaluatePharma analysts say.

One of the exceptions to declining sales is Pfizer’s Retacrit, a biosimilar version of Epogen that is expected to generate a double-digit CAGR per EvaluatePharma analysis. Retacrit has been available in Europe since 2008, but its regulatory path in the United States has included some sped bumps, including the issuance of an FDA complete response letter two years ago. But FDA’s Oncologic Drugs Advisory Committee (ODAC) near the end of May recommended approval of Pfizer’s proposed epoetin alfa biosimilar across all indications. This represents the first time a biosimilar erythropoiesis-stimulating agent (ESA) has been recommended for approval by an FDA advisory committee. The ODAC’s favorable recommendation was based on its review of the totality of evidence, including demonstration of comparable efficacy and safety of biosimilar epoetin alfa to its reference product, Epogen and Procrit (epoetin alfa).

This positive recommendation marks an important milestone for Pfizer’s U.S. biosimilars portfolio, according to the company, following the U.S. approval and launch of Inflectra. In late November 2016, Pfizer began shipping Inflectra (infliximab-dyyb) for injection to U.S. wholesalers. Inflectra is a biosimilar version of Remicade (infliximab), which is an anti-tumor necrosis factor alpha (TNFa) mAb and blockbuster autoimmune disorders medicine that is marketed across the globe by J&J, Merck, and Mitsubishi Tanabe Pharma.

Inflectra marks the first biosimilar monoclonal antibody and only the second biosimilar to be made available in the United States. Sandoz’s Zarxio, which is a biosimilar version to Amgen’s Neupogen (filgrastim), was the first biosimilar product to gain FDA marketing clearance during March 2015. Inflectra was approved for the treatment of moderate to severely active Crohn’s disease; moderate to severely active ulcerative colitis; moderate to severely active rheumatoid arthritis; active ankylosing spondylitis; active psoriatic arthritis; and chronic severe plaque psoriasis.

Regarding Remicade, near the end of May a UK competition watchdog accused Merck & Co. of operating an unfair discount scheme for the medicine that it said was designed to restrict competition from so-called biosimilar copies. The Competition and Markets Authority (CMA) reportedly said it had provisionally found the U.S. company’s European unit, Merck Sharp & Dohme, had abused its dominant position via the scheme, opening it up to potential financial penalties. According to a Reuters report, MSD said it did not believe it had broken competition rules. MSD said it was cooperating fully with the CMA, and was confident the proceedings would demonstrate the company had complied with the law.

As outlined in the Reuters article, the drug is proving an important test for the emerging biosimilars industry. Remicade was the first antibody drug for which copycat versions were approved by European regulators, resulting in the launch of discounted products from biosimilar drugmakers such as South Korea’s Celltrion, which works with Pfizer.

Per the Reuters article, a person familiar with the investigation said MSD offered a discount to customers who continued to buy Remicade in the same quantities but not if they started buying biosimilars, which amounted to an incentive not to switch. While Remicade remains a big seller for Merck, sales have been declining in the face of biosimilar competition. The TNFa mAb is projected to be the third-best-selling anti-rheumatic product based on 2022 global sales per EvaluatePharma.

Back to Celltrion: In February 2017, the company’s biosimilar version of Roche’s blockbuster anti-cancer agent Rituxan/MabThera (rituximab) was granted marketing authorization by the European Commission. Truxima represents the first biosimilar mAb approved in an oncology indication worldwide.

Truxima is approved in the EU for treating people with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis and microscopic polyangiitis. This approval was based on the totality of evidence submitted to the EMA showing compelling similarity between Truxima and reference rituximab in terms of efficacy, safety, immunogenicity, pharmacodynamics and pharmacokinetics in patients with RA and advanced follicular lymphoma, a type of NHL. Those studies were conducted in more than 600 patients and include data up to 104 weeks.

Biosimilars have the potential to offer cost savings for healthcare systems and therefore the potential to increase patient access to biological therapies. “Assuming the price of biosimilar rituximab is 70 percent compared to reference rituximab, and the market share of biosimilar rituximab is 30 percent (first year), 40 percent (second year) and 50 percent (third year), over this three-year time period the budget savings across the 28 countries of the EU would be around €570 million,” said Prof. László Gulácsi, Head of Department of Health Economics, Corvinus University of Budapest; HTA Consulting Budapest, Hungary.

“This equates to 49,000 new RA, NHL and CLL patients who could be receiving life-changing treatment which is clearly a huge aggregate health-gain at both a national and EU level.”