While much of the news about clinical breakthroughs this summer came out of the American Society of Clinical Oncology annual meeting (below), biotechs focused on immunomodulatory and rare diseases were busy moving their discoveries closer to market.
In the immunomodulatory area, some players are tossing out only enough information to pacify investors. Novartis says secukinumab, an interleukin 17A inhibitor, bested etanercept (Enbrel) in a head-to-head trial in patients with psoriasis. Endpoints included PASI-75. Celgene says apremilast achieved its primary endpoint of ACR-20 at Week 16 in treatment-naive patients with psoriatic arthritis. Both manufacturers promise to tell the full stories at medical congresses later this year.
On the rare disease front, Sanofi, too, is tight-lipped about outcomes from its pivotal study of SAR302503, a JAK-2 inhibitor for myelofibrosis, a rare blood cancer. The primary endpoint was a reduction in spleen volume, which Sanofi says it achieved. Data will be released later this year. In California, a tiny biotech, Alvine, reports success with a phase 2 study of AVL003 in patients with celiac disease. The drug breaks down gluten to prevent inflammation. AbbVie promptly bought the rights to the drug, which is moving on to a phase 2b trial of 500 patients.
After two once-promising treatments for blood cancers didn’t meet their trial endpoints, one hit the dustbin. Eli Lilly ended development of enzastaurin after the kinase inhibitor failed to show a significant improvement in disease-free survival in patients with diffuse large B-cell lymphoma. Pfizer says inotuzumab missed its endpoints in a study of patients with CD22+ non-Hodgkin’s lymphoma, but the drugmaker will sift subpopulation data for clues to other potential uses. Inotuzumab is an antibody-drug conjugate.
At Baxter, investigators are also analyzing subgroup data for signs of hope after Gammagard was no better than placebo in a late-stage study of Alzheimer’s patients. Gammagard is an immune-boosting agent.
Ketamine — known as Special K among those who abuse the animal sedative for a quick high — is under study as a possible antidepressant. Johnson & Johnson used a reformulation of the drug in research involving 72 hard-to-treat patients. Response rates after 1 day were 64% in the ketamine group versus 28% in a sham group, and after a week, ketamine response remained at 46% versus 28%. The drug is a long way from market, but J&J views it as a legitimate prospect.... European regulators have approved two biosimilar versions of infliximab (Remicade). Infliximab is the biggest biologic to gain biosimilar competition in Europe. It has patent protection there until 2015 and in the United States until 2018.
|BIOLOGICS IN DEVELOPMENT|
|SELECTED FDA BIOLOGIC AND SPECIALTY DRUG APPROVALS, MAY 4–JULY 14, 2013|
|Date (type)||Manufacturer||Drug (trade name); administration||Indication||Notes|
|New marketing approvals|
|May 15 (NDA)||Bayer||radium Ra 223 dichloride (Xofigo); IV injection||Castration-resistant prostate cancer||Radiopharmaceutical delivers radiation directly to bone tumors, sparing surrounding tissue. OS advantage is 2.8 months vs. placebo.|
|May 29 (NDA)||GlaxoSmithKline||dabrafenib (Tafinlar); oral||Unresectable or metastatic melanoma with BRAF V600E mutation||Companion diagnostic, THxID BRAF, must confirm mutation prior to use. FDA approved THxID BRAF May 29.|
|May 29 (NDA)||GlaxoSmithKline||trametinib (Mekinist); oral||Unresectable or metastatic melanoma with BRAF V600E or V600K mutation||Also requires presence of mutation, identified through THxID BRAF test. Trametinib is not approved as combination therapy with dabrafenib.|
|June 26 (BLA)||GlaxoSmithKline||recombinant coagulation factor IX (Rixibus); IV infusion||Control/prevention of bleeding, perioperative management, and prophylaxis to prevent or reduce frequency of bleeding in adults with hemophilia B||First new recombinant factor IX approved for hemophilia B in more than 15 years. Biogen Idec and Novo Nordisk have long-acting factor IX products in late-stage development.|
|July 12 (NDA)||Boehringer Ingelheim||afatinib (Gilotrif); oral||First-line treatment of non–small-cell lung cancer with EGFR exon 19 deletions or exon 21 substitution mutations||FDA-approved companion diagnostic must confirm EGFR mutation prior to use.|
|May 15||Genentech||erlotinib (Tarceva); oral||First-line treatment of non–small-cell lung cancer with EGFR exon 19 deletions or exon 21 substitution mutations||FDA-approved companion diagnostic must confirm EGFR mutation prior to use.|
|July 11||Celgene||lenalidomide (Revlimid); oral||Mantle-cell lymphoma, after failure of two prior therapies including bortezomib||First approved in 2005, lenalidomide is second-line therapy for MM. Celgene has new data it will use to petition the FDA for first-line MM use.|
|SELECTED FDA-RELATED ACTIVITIES, MAY 4–JULY 14, 2013|
|Manufacturer||Drug (trade name)||Type of drug||Proposed use||Notes|
|Gilead||sofosbuvir, formerly GS-7977||nucleotide analogue inhibitor of HCV||Chronic HCV: with RBV for genotypes 2, 3; with RBV and peg-IFN for genotypes 1, 4, 5, 6||Tentative FDA review date is Dec. 8.|
|Roche||obinutuzumab||humanized IgG1 monoclonal antibody||CLL||FDA approval deadline for potential “Rituxan successor” is Dec. 20.|
|Marketing approval denied|
|Aveo||tivozanib||Oral, once-daily tyrosine kinase inhibitor||Advanced renal cell carcinoma||Rejected June 10 over “uninterpretable” data showing positive PFS but a negative OS benefit.|
| BLA=biologics license application, CLL=chronic lymphocytic leukemia, EGFR=epidermal growth factor receptor, HCV=hepatitis C virus, IV=intravenous, MM=multiple myeloma, NDA=new drug application, OS=overall survival, PFS=progression-free survival, RBV=ribavirin. |
Sources: Bloomberg, FDA, FierceBiotech, Nature, New York Times, the Street.com, and manufacturers’ news releases and product labeling.
All clinical trials described in this column are phase 3, randomized, controlled studies unless otherwise specified.