Viruses. You don’t want one — unless it’s one that attacks disease instead of promoting it. And yes, such a thing exists.
In a trial involving patients with stage 3 or 4 melanoma, talimogene laherparepvec, or T-vec, Amgen’s cancer-fighting virus, came out swinging against granulocyte-macrophage colony-stimulating factor (GM-CSF). In an open-label study, median overall survival (OS) in patients receiving T-vec was 23.3 months, 4.3 months more than patients given GM-CSF. T-vec is injected into cancer tissue, where it replicates and releases antitumor antigens.
The irony in T-vec’s development is that it was shepherded at Amgen by Roger Perlmutter, MD, PhD, who is now Merck’s R&D chief. Perlmutter is pushing hard for quick FDA approval of Merck’s own immunotherapy, MK-3475. Merck is wrapping up a phase 3, head-to-head melanoma trial of the PD-1 inhibitor against ipilimumab (Yervoy), and in late 2013, MK-3475 demonstrated an 81% 1-year OS in a phase 1B trial involving more than 1,000 patients with advanced metastatic skin and lung cancers.
T-vec and MK-3475 are just two immunotherapies on the forefront of development; two more are also nearing the R&D finish line. Further back, there’s CTL019, an interesting entry that might remind you of Provenge. The personalized regimen draws T cells from a patient’s blood, engineers them to hunt for cancer cells that express certain proteins, then re-injects them into the body. In an early-stage trial, CTL019 induced complete remission in 19 of 22 children and 7 of 32 adults with leukemia. Five children relapsed. Novartis has licensed CTL019 from the University of Pennsylvania.
With a new indication and a black box warning about heart failure and the risk of vascular events, ponatinib (Iclusig) is back on the market. The Food and Drug Administration asked Ariad Pharmaceuticals to stop sales and marketing last October after real-world experience with the kinase inhibitor resulted in greater incidence of blood clots than what the drug’s label showed. As part of its new agreement with the FDA, Ariad will engage in postmarketing pharmacovigilance activities.
An FDA review prepared in advance of an advisory committee vote on vedolizumab, Takeda’s leukocyte-targeting antibody for people with ulcerative colitis (UC) and Crohn’s disease, raised concern about the drug’s potential to cause progressive multifocal leukoencephalopathy (PML). Nobody in vedolizumab clinical trials developed PML, but that was also true when natalizumab (Tysabri) hit the market in 2004. Since then, 343 people taking natalizumab have developed PML. Natalizumab was later relaunched with a diagnostic test to detect the JC virus, which causes the demyelinating condition.
Days after the release of the FDA review on vedolizumab, the advisory panel played down the danger, convinced that Takeda adequately warns prescribers and patients about it in product labeling. But the committee split on when treatment with the drug should be initiated. The group voted 20–0 that the drug was effective as maintenance therapy, but 12–9 that the drug was appropriate for induction therapy. The FDA will decide by February 18 on a UC indication and by June on Takeda’s Crohn’s disease application.
The FDA told 23andMe to stop selling its personal genome service until it gets marketing clearance. By sending 23andMe a saliva sample, consumers can get information on BRCA-related genetic risk or warfarin sensitivity, among other things. The company will comply but still offers raw genetic data without interpretation.
|SELECTED FDA APPROVALS OF BIOLOGIC AND SPECIALTY DRUGS, NOV. 15, 2013–JAN. 15, 2014|
|Date (type)||Manufacturer||Drug (trade name); administration||Indication||Notes|
|New marketing approvals|
|Nov. 22, 2013 (NDA)||Janssen||simeprevir (Olysio); oral||In combination with peginterferon alfa and ribavirin, in patients with genotype 1 chronic HCV infection||Protease inhibitor cut the amount of interferon that hepatitis C patients require, compared with two other drugs in its class, telaprevir (Incivek) and boceprevir (Victrelis). Sofosbuvir approval days later, however, eliminated need in most patients for an interferon regimen.|
|Dec. 6, 2013 (NDA)||Gilead||sofosbuvir (Sovaldi); oral||Chronic HCV as part of a combination regimen with ribavirin in all 4 genotypes. Addition of interferon alfa is recommended in patients with genotypes 1 and 4 except in patients ineligible for interferon.||First all-oral treatment for hepatitis C without a need for co-administration of interferon. AWP of a 24-week supply is $84,000.|
|Dec. 20, 2013 (BLA)||Novo Nordisk||coagulation factor XIII A-subunit (recombinant), (Tretten); IV injection||Prophylaxis of bleeding in patients with congenital factor XIII A-subunit deficiency||Orphan drug is the first treatment for patients with this rare genetic disorder, seen in about 1 in 5 million births. The FDA approved Tretten on the basis of a 77-person trial.|
|SELECTED FDA-RELATED ACTIVITIES, NOV. 15, 2013–JAN. 15, 2014|
|Manufacturer||Drug (trade name)||Type of drug||Proposed use||Notes|
|Sanofi||alemtuzumab (Lemtrada)||recombinant DNA-derived humanized monoclonal antibody||Relapse-remitting multiple sclerosis||Dec. 30 CRL described the FDA’s concern about “serious adverse effects,” primarily the risk of autoimmune disorders. The FDA required new clinical trials with different designs; Sanofi is appealing. Alemtuzumab was approved in Canada Dec. 13.|
AWP=average wholesale price, BLA=biologics license application, CRL=complete response letter, HCV=hepatitis C virus, NDA=new drug application
Sources: Barts and the London School of Medicine and Dentistry, Bloomberg, CBS News, FDA, FierceBiotech, healthcentral.com, Journal of Biomedical Biotechnology, the Motley Fool, and manufacturers’ news releases and product labeling
All clinical trials described in this column are phase 3, randomized, controlled studies unless otherwise specified.