Gilead Sciences is likely to be first to market with an oral drug for hepatitis C, after releasing persuasive data from three phase 3 studies of sofosbuvir. With regulatory filings planned this quarter, Gilead could conceivably win Food and Drug Administration approval of the nucleotide previously known as GS-7977 by early next year.
In two of the studies, Gilead studied sofosbuvir plus ribavirin (RBV) against the existing standard of care, RBV and pegylated interferon alfa-2a (peg-IFN). Patients with genotypes 2 and 3 given sofosbuvir achieved sustained virologic response (SVR) in half the time of those in the RBV/peg-IFN arm. Patients with genotypes 1, 4, 5, and 6 achieved higher rates of SVR after 12 weeks. And in a third study, sofosbuvir yielded SVR in 50 and 73 percent of patients who had failed interferon-based therapy, at weeks 12 and 16, respectively.
The allure is that sofosbuvir treats hepatitis C without the use of interferons, whose side effects lead to poor adherence with older hepatitis C treatments. According to a Fierce Biotech report, physicians are advising treatment-naive patients to wait until sofosbuvir is approved, preferring to start them on what is likely to become the new standard of care.
Gilead isn’t likely to be alone at the top of the hill for long. AbbVie, the drug-making unit of what used to be Abbott Labs, has an agent in phase 3, and several other companies are hot on their heels.
Eli Lilly’s stomach cancer antibody, ramucirumab, hit statistical significance with a 1.4-month overall survival (OS) benefit versus placebo. Analysts, however, generally judged the gain underwhelming.
In a trial involving patients with advanced kidney cancer, those given tivozanib had a median OS of 28.8 months. But median OS for the comparator arm, sorafenib (Nexavar), was longer — 29.3 months. The AVEO/Astellas drug did show a statistically significant improvement in progression-free survival.
Celgene’s oral PDE4 for psoriasis, apremilast, achieved PASI-75 in 33 percent of patients after 16 weeks versus 5 percent of patients given placebo. The phase 3 reductions fell below the 41 percent who reached PASI-75 in a phase 2 study.
The disappointing news continued at Eli Lilly, which abandoned its program to develop tabalumab as a rheumatoid arthritis treatment because of lack of efficacy. Lilly will continue to study the agent as a potential therapy for lupus.
Using darbepoetin alfa (Aranesp) to treat anemia has no effect on morbidity and mortality in patients with systolic heart failure. Amgen’s RED-HF study failed to meet its primary endpoint of time to death.
Hemispherx is appealing the FDA’s rejection of Ampligen, which has been in development for chronic fatigue syndrome for 20 years. Ampligen was first turned down in 2009. The FDA wants another clinical trial.
Cangene is seeking approval of a botulism antitoxin vaccine, now that the FDA has blessed the antibioterrorism shot as effective.... Stem cell transplantation reduced mortality at day 100 in patients with leukemia and lymphoma. Now, Gamida Cell will apply for U.S. approval of StemEx.... Hopes were high that MVA85A would become the first tuberculosis vaccine in 90 years, but a study in the Lancet documented only a modest immune response, insufficient to protect against the disease.... Fecal transplants to treat C. difficile infection may not be on the fringes of medicine much longer, now that the New England Journal of Medicine has published a randomized, controlled study finding the practice far superior to antibiotic therapy.
|SELECTED FDA BIOLOGIC AND SPECIALTY DRUG APPROVALS, JAN. 16–MARCH 15, 2013|
|Date (type)||Manufacturer||Drug (trade name); administration||Indication||Notes|
|New marketing approvals|
|Jan. 29 (NDA)||Genzyme/Isis||mipomersen (Kynamro); SC injection||Reduction of low-density lipoprotein, apolipoprotein B, total cholesterol, and non-high density lipoprotein in patients with HoFH||FDA advisory committee 9–6 vote illustrated concerns about carcinogenic and hepatotoxic side effects; Isis must conduct 4 postmarketing studies, including a safety registry.|
|Feb 1. (NDA)||Hyperion||glycerol phenylbutyrate (Ravicti); oral||Management of UCDs that cannot be managed by dietary protein restriction and/or amino acid supplementation alone||For adults and children ≥2 years old, orphan drug targets enzyme deficiencies that lead to brain-damaging ammonia buildup in blood.|
|Feb. 8 (NDA)||Celgene||pomalidomide (Pomalyst); oral||MM in patients who have had at least two prior therapies, including lenalidomide (Revlimid) and bortezomib (Velcade), with disease progression ≤60 days of completion of last therapy||Thalidomide analogue is the second MM drug approved in the past year. Modulates immune system to kill cancer cells and inhibit proliferation.|
|Feb. 22 (BLA)||Genentech||ado-trastuzumab emtansine (Kadcyla); IV infusion||HER2-positive metastatic breast cancer for patients who have previously received trastuzumab (Herceptin) and a taxane||The former T-DM1 combines trastuzumab with a chemotherapy targeting cancer cells but sparing healthy cells. 5.8-mo. OS benefit compared with lapatinib (Tykerb) and Xeloda.|
|Jan. 23 (BLA)||Genentech||bevacizumab (Avastin)||Metastatic colorectal cancer with intravenous 5-fluorouracil–based chemotherapy for second-line treatment||Label already had first-line indication; change permits patients to stay on bevacizumab in combination with a new chemotherapy after progression.|
|SELECTED FDA-RELATED ACTIVITIES, JAN. 16–MARCH 15, 2013|
|Manufacturer||Drug (trade name)||Type of drug||Proposed use||Notes|
|Boehringer Ingelheim||afatinib (Tomtovok)||Next-generation TK inhibitor of EGFR||Locally advanced or metastatic NSCLC with EGFR mutation||FDA granted priority review Jan. 17; approval decision in 3rd quarter.|
|Novo Nordisk||degludec (Tresiba)||Long-acting insulin analogue||Type 2 diabetes||CRL issued Feb. 10; FDA wants new cardiovascular safety study before approval.|
|GlaxoSmith-Kline||dolutegravir||integrase inhibitor||HIV/AIDS||FDA granted priority review Feb. 15; approval decision by Aug. 17.|
| BLA=biologics license application, CRL=complete response letter, EGFR=epidermal growth factor receptor, HoFH= homozygous familial hypercholesterolemia, IV=intravenous, MM=multiple myeloma, NDA=new drug application, NSCLC-non–small-cell lung cancer, OS=overall survival, SC=subcutaneous, TK=tyrosine kinase, UCD= urea cycle disorders. |
Sources: FDA, FierceBiotech, manufacturers’ news releases, product labeling, SEC filings, weblogs, and wire reports.