Biologics in Development

3 New Biologics To Be Worth $14B in Sales by 2019


Katherine T. Adams

Eleven recently- or soon-to-be-released biologics may hit blockbuster status within five years, according to Thomson Reuters’ annual “Drugs to Watch” report. The inclusion of 11 drugs in the 2015 report is notable, as only three made the list in 2014.

Nivolumab (Opdivo) tops this year’s list. Bristol Myers-Squibb’s anticancer agent could reach $5.6 billion in sales by 2019. Alirocumab (Praulent), Regeneron and Sanofi’s monoclonal antibody to treat hypercholesterolemia and now under priority review at the FDA, comes in second at $4.4 billion. LCZ-696, a Novartis combination agent for chronic heart failure, rounds out the top three, with predicted sales of $3.7 billion by 2019.

Specialty drugs are driving the drug-dollar market, says Larry Whisenant, director of specialty pharmacy operations at McKesson Specialty Health. As more specialty products emerge, he adds, they will continue to be a main cost factor—about 20 to 60%—for payers and employers. Biosimilars will mitigate this trend, but the timing and impact remain to be seen. Whisenant says that 2016 “may be a little early, but certainly within the next two to three years, depending on level of acceptance.”

Another factor that will affect specialty drug spending, says Whisenant, is that PBMs and payers are consolidating in a big way, as with UnitedHealth Group’s acquisition of Catamaran. “What you see there is 75% of the market driven by three PBMs.” The effect of this consolidation of power is that as new specialty products become available and widen the market, PBMs are likely to drive harder bargains or offer more exclusive formularies.

Here come the biosimilars

On March 6, the FDA approved filgrastim-sndz, (Zarxio)—a biosimilar of Amgen’s Neupogen, which prevents infections in cancer patients—the first biosimilar to be approved in the United States under the 351k pathway. Hot on Sandoz’s heels is Apotex, whose filgrastim (Grastofil) biosimilar application is under FDA review. Experts see, though, a number of obstacles slowing biosimilars’ market penetration: Physicians who don’t understand the approval process, patient acceptance, litigation, and questionable cost savings, to name a few.

That didn’t deter Merck from saying at March’s Cowen Healthcare Conference that five biosimilars would be submitted for global approval this year and next. In the United States, Merck is taking aim at AbbVie’s Humira, J&J’s Remicade, Sanofi’s Lantus, Roche’s Herceptin, and Amgen’s Enbrel. Existing agreements, however, would prevent Merck from launching an Enbrel biosimilar in the United States.

Clinical trial updates

Bevacizumab (Avastin) plus chemotherapy improved overall survival (OS) by nearly five months compared with chemotherapy alone for women with platinum-sensitive recurrent ovarian cancer, according to data presented at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The GOG0213 trial marked the first time a phase 3 study has shown OS improvements in this population.

PCSK9 inhibitors were in the spotlight at the American College of Cardiology’s Annual Scientific Session. Monthly dosing of alirocumab (Praluent) reduced hypercholesterolemia in patients with high cardiovascular risk, according to data from the ODYSSEY CHOICE I and CHOICE II trials. At the same conference, Amgen presented one-year data from the phase 2 and phase 3 OSLER trials of evolocumab (Repatha). In open-label studies, evolocumab reduced adjudicated cardiovascular events. Results of both studies were published in the New England Journal of Medicine. Both agents are under review at the FDA.

The PERSIST-1 phase 3 trial examining pacritinib, an oral JAK2 multikinase inhibitor for treatment of patients with myelofibrosis, met its primary endpoint. Compared with best available therapy, pactritinib resulted in a statistically significant increase in patients achieving a 35% or greater reduction in spleen volume… Takeda will terminate the phase 3 MONET-A trial, which studied motesanib in patients with stage 4, non–small-cell lung cancer (NSCLC), after the oral angiokinase inhibitor failed to meet its progression-free survival endpoint.

Have you heard?

Sofosbuvir (Solvaldi) and ledipasvir/sofosbuvir (Harvoni) got labeling updates after the FDA warned about postmarketing cases of bradycardia when either of the hepatitis C agents are co-administered with amiodarone… Genetic testing in metastatic NSCLC patients and subsequent molecular biomarker-guided therapy is cost-effective compared with a chemotherapy-treatment approach without molecular testing, according to a study published in the Journal of Thoracic Oncology… Now that the FDA has said that 23andMe can provide an alert about Bloom Syndrome in its genetic profiles to prospective parents, the company plans to begin developing drugs based on its massive genetic database. CEO Anne Wojcicki says engaging consumers in drug development could be an industry game-changer.

In the rush to spend, queries give pause

In the wake of fast-growing expenditures on biologic therapies, opinion leaders are raising questions about how biologics and other specialty drugs are evaluated and used.

Maurie Markman, MD, clinical professor of medicine at Drexel University in Philadelphia, asks whether the regimen in a phase 3 trial comparing FOLFOXIRI versus FOLFIRI plus bevacizumab (Avastin) as first-line treatment of metastatic colorectal cancer is justified when it is associated with an “impressive” risk of toxicities. Speaking on OncologyLive, Markman also questioned the propriety of a phase 3 trial that explored the use of erlotinib (Tarceva), an epidermal growth factor receptor (EGFR) inhibitor, as maintenance therapy for patients with ovarian cancer when clinical data have shown that EGFR is not a clinically relevant target.

Writing in Pain Medicine News, New York anesthesiologist S.J. Slavin argues that, in the long run, cost reduction and quality-of-life improvements cannot be attained together. More people in the United States “have better access to the care they would want than the people who can afford to purchase private insurance in England,” he says, and questions what, specifically, we should look for in health care quality.

On Scientific American’s blog, Harvard Med student Ilana Yurkiewicz asks provocative questions about why aren’t we making greater use of agents that studies have shown to work and be cost-effective. Yurkiewicz cites the evidence for hydroxyurea in sickle cell disease, the Lyme Disease vaccine, and tamoxifen or raloxifene for breast cancer prevention in high-risk patients.

Selected FDA approvals of biologics and other specialty drugs, Feb. 16–April 1, 2015

New marketing approvals
Date (type) Manufacturer Drug (trade) name; administration Indication Notes
Feb. 23 (NDA) Novartis panobinostat (Farydak); oral In combination with bortezomib and dexamethasone for multiple myeloma in patients who have received ≥2 prior regimens including bortezomib and an immunomodulatory agent Histone deacetylase inhibitor carries a black box warning about severe and fatal cardiac ischemic events (4% of patients in clinical trials), arrhythmias (12%) and severe diarrhea (25%).
March 6 (BLA) Sandoz filgrastim-sndz (Zarxio); subcutaneous injection All five indications for filgrastim (Neulasta) First biosimilar approved in U.S. under 351k pathway. Zarxio achieved biosimilarity, not interchangeability.
March 10 (BLA) United Therapeutics dinutuximab (Unituxin); intravenous infusion In combination with GM-CSF, IL-2, and 13-cis-retinoic acid in children with high-risk neuroblastoma with partial response to a prior first-line agent GD2-binding monoclonal antibody carries a black box warning about severe neuropathic pain. IV opioids may be administered before, during, and after infusions.
New indications of previously approved treatments
March 4 (sBLA) Bristol-Myers Squibb nivolumab (Opdivo) Metastatic squamous NSCLC with progression on or after platinum-based chemotherapy Previously approved for unresectable metastatic melanoma.
March 25 (sBLA) Regeneron aflibercept (Eylea) Diabetic retinopathy in patients with diabetic macular edema New indication based on 2 RCTs in patients age 23 to 87.
BLA=biologics license application, GM-CSF=granulocyte-macrophage colony-stimulating factor, IL=interleukin, IV=intravenous, NDA-new drug approval, NSCLC=non-small cell lung cancer, RCT=randomized, controlled trial, sBLA=supplemental biologics license application, sNDA=supplemental new drug application.
Sources: FDA, Fierce Biotech, and manufacturers’ package inserts.

All clinical studies mentioned in this article are phase 3 unless otherwise stated.

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