As anyone who has watched the field with some regularity knows, cancer immunotherapy is a tough field to hoe. Provenge is the only therapeutic vaccine for cancer to make it all the way to U.S. Food and Drug Administration approval, and it’s struggling to gain market share. Many more — see GVAX, Canvaxin, and FavID — looked lively in phase 2 studies, only to die a quiet death after fizzling in phase 3.
Add Stimuvax to the list of those stumbling on a bigger stage. Merck and Oncothyreon’s immunotherapy for patients with unresectable, stage 3 non–small-cell lung cancer failed to demonstrate a statistically significant overall survival benefit compared with placebo. Though researchers said they would pull back to take a closer look at favorable data in some study populations, the FDA rarely approves a drug on the basis of subgroup analyses if it missed its primary endpoint.
“It’s now becoming clear that therapeutic cancer vaccines might be most efficacious in earlier-stage cancers, after they are treated and have minimum residual disease,” analyst Dee Kotak wrote on Seeking Alpha’s Web site in the days that followed. Some vaccine developers have made the same contention: Get in early to give the immune system time to rev up. But payers, who tend to view Provenge’s cost as additive to — rather than in place of — chemotherapies, are likely to look for hard evidence of earlier-stage efficacy and cost offsets before giving high-cost immunotherapies favorable formulary positions.
Still, the field remains a hotbed of research, with clinical trials underway for therapeutic vaccines designed to treat bladder, blood, brain, breast, cervical, kidney, lung, skin, pancreatic, and prostate cancers.
Eisai faces the same challenge that Merck and Oncothyreon share — making lemonade out of patient subset data — after its ovarian cancer candidate, farletuzumab, went sour in an 1,100-patient trial. Farletuzumab failed to show a statistically significant progression-free survival benefit in women with relapsed disease. The Japanese manufacturer said it would evaluate what it believes may be encouraging subpopulation outcomes to determine a new development strategy for the molecule.
Gilead released positive topline results of the first of three phase 3 trials of sofosbuvir (formerly GS-7977), part of an all-oral, interferon-free regimen for hepatitis C. In patients with genotypes 2 and 3, a cocktail of sofosbuvir and ribavirin left no detectable sign of the disease in 78 percent of patients after 12 weeks.
Gilead will roll out data from two more phase 3 studies this year, with an eye toward a mid-year FDA filing.
An FDA advisory committee voted 14–0 to recommend approval of GlaxoSmithKline’s H5N1 avian flu vaccine. The unanimous vote stood in contrast to 2007, when the world was in panic over bird flu and hungry for any vaccine. At the time, Sanofi Pasteur sent the FDA a first-generation H5N1 vaccine that provided protection to only 45 percent of adults who got the highest dose. The FDA held its nose and approved the Sanofi vaccine anyway, conceding that it was safe but not necessarily effective.
Another FDA advisory committee voted 8–4 to recommend approval of Novo Nordisk’s long-acting insulin analogue, degludec (Tresiba), but attached what could be a costly string: Concerned about heart risks, the panel also agreed to recommend that Novo Nordisk conduct a cardiovascular study prior to formal marketing approval. Should the FDA ultimately require the study, it could delay the launch of degludec by as much as a year.
Now that natalizumab (Tysabri) is marketed with a test to detect whether a patient harbors the John Cunningham virus (JCV), Biogen Idec wants the FDA’s blessing for first-line use of the powerful multiple sclerosis drug. Natalizumab is generally reserved for patients with advanced cases of relapse-remitting MS because it carries the risk of progressive multifocal leukoencephalopathy (PML). Exposure to JCV is required for the development of PML.
—Michael D. Dalzell
|SELECTED FDA BIOLOGIC AND SPECIALTY DRUG APPROVALS, NOV. 1, 2012–JAN. 15, 2013|
|Date (type)||Manufacturer||Drug (trade name); administration||Indication||Notes|
|New marketing approvals|
|Nov. 6 (NDA)||Pfizer||tofacitinib (Xeljanz); oral||Moderate to severe rheumatoid arthritis, alone or in combination with nonbiologic DMARDs||First oral biologic for RA and first-to-market Janus kinase inhibitor. FDA will require postmarketing study of 2 doses plus a comparator arm to study effects on infections, cancer, and heart disease.|
|Nov. 29 (NDA)||Exelixis||cabozantinib (Cometriq); oral||Progressive metastatic medullary thyroid cancer||Second FDA-approved drug to treat this rare form of cancer. Total market is 500–700 patients per month. Treatment cost is $9,900 per month. Phase 3 trials showed PFS of >7 months compared with placebo.|
|Dec. 14 (NDA)||Ariad||ponatinib (Iclusig); oral||Adults with CML and Ph+ALL who are intolerant of, or whose disease is refractory to, previous TK therapy||Targets CML cells with T315i mutation, which makes them resistant to other TK inhibitors such as dasatinib (Sprycel). Black box warns about arterial thrombosis and liver toxicity.|
|Dec. 21 (NDA)||NPS Pharmaceuticals||teduglutide [rDNA origin] (Gattex)||Adults with short bowel syndrome who are dependent on parenteral support||The first drug approved for short bowel syndrome since 2004, teduglutide will set payers back $295,000 per year. Prevalence of the disease is unknown, but estimates are that 2 of every 1 million people may have it.|
|SELECTED FDA-RELATED ACTIVITIES, NOV. 1, 2012–JAN. 15, 2013|
|Manufacturer||Drug (trade name)||Type of drug||Proposed use||Notes|
|Roche/Genentech||trastuzumab emtansine (Kadcyla)||Antibody-drug conjugate pairs trastuzumab (Herceptin) with a cytotoxic agent to target cancer cells and spare healthy tissue||HER-2+ breast cancer||FDA granted priority review; PDUFA date Feb. 26.|
CML=chronic myeloid leukemia, DMARD=disease-modifying antirheumatic drug, CRL=complete response letter, NDA=new drug application, PDUFA=prescription drug user fee act, PFS=progression-free survival, Ph+ALL=Philadelphia chromosome-positive acute lymphoblastic leukemia, RA=rheumatoid arthritis, TK=tyrosine kinase.
Sources: FDA, FierceBiotech, manufacturers’ news releases, product labeling, SEC filings, weblogs, and wire reports.
All clinical trials described in this column are phase 3, randomized, controlled studies unless otherwise specified.