Abstract
Approvals, research, conference coverage.
Selected late-stage trials
Amgen released additional data from two previously reported studies of denosumab. The investigational osteoporosis therapy reduced new spinal fractures by 68 percent and hip fractures by 40 percent compared to placebo in post-menopausal women with osteoporosis. And, in a head-to-head comparison with oral alendronate (Fosamax), three quarters of patients said they preferred the twice-yearly, subcutaneous denosumab injections to a weekly tablet.
Amgen’s TNF-α inhibitor, etanercept (Enbrel), did not fare as well in the first head-to-head comparison of two biologic psoriasis treatments. In a randomized trial of 903 patients with moderate to severe plaque psoriasis, Centocor declared its interleukin-12/-23 blocker uste kinumab (Stelara) superior to etanercept on the basis of 12-week outcomes. Patients given ustekinumab received low- or high-dose injections twice during the study period; 68 percent of those given the lower dose and 74 percent of those given the higher dose experienced a 75 percent or greater reduction in psoriasis severity (PASI-75). Among patients treated with twice-weekly injections of etanercept (50 mg), 57 percent achieved PASI-75. Amgen downplayed the results, saying that the long-term efficacy of the new product had not yet been established.
Meeting highlights
ASCO Breast Cancer Symposium
September 2008
Interim results from a study evaluating molecular breast imaging (MBI) as a screening method show that MBI is a better method than mammography in women with mammographically dense breasts, as well as in women who are at increased risk for breast cancer. MBI detected three times as many cancers as mammography. Of the 13 cancers that were detected, 8 were detected by MBI alone.
Researchers measuring quality of life among women with HER2-positive, metastatic breast cancer treated with either lapatinib (Tykerb) alone or lapatinib with trastuzumab (Herceptin) reported a similar QOL among patients who received combination therapy as those given lapatinib alone. The fact that the combination therapy — for which studies have shown a significant clinical benefit — maintained QOL was heralded as a key consideration for patient care.
The combination of oxaliplatin chemotherapy and trastuzumab in patients with HER2-positive breast cancer was reported to be well tolerated, with no significant toxicities. … Trastuzumab monotherapy was compared to trastuzumab in combination with chemotherapy as a first-line treatment for HER2-positive breast cancer. Results suggest equivalent efficacy and similar safety and tolerability profiles for the two approaches, but phase 3 trials are needed to confirm these results. ... Another study found no cardiac events associated with a regimen of bevacizumab (Avastin) and trastuzumab, or when bevacizumab was combined with docetaxel chemotherapy in HER2-positive patients.
Recombinant human C1 inhibitor (Rhucin), derived from the milk of genetically modified rabbits, was denied approval by the European Medicines Agency in March. In response, Pharming, a Dutch biotech, issued a safety analysis of more than 300 administrations —half of which were repeat treatments — showing no adverse incidents. Pharming plans to submit a biologics license application with the U.S. Food and Drug Administration by the end of this year. Rhucin was developed for the treatment of hereditary angioedema, and is a potential competitor to Dyax’s HAE drug, DX-88 (ecallantide), which has orphan and fast track status in the United States. Dyax included recent phase 3 data of DX-88, documenting symptom reductions in 94 percent of HAE patients taking the drug, in its September BLA.
Well known as a wrinkle cure, botulinum toxin type A (Botox) also works for chronic migraines, according to Allergan, which completed a phase 3 study that documented a reduction in the number of headache days. A second phase 3 study, using headache days as the endpoint, showed reductions in both headache days and headache episodes. Allergan intends to file a supplemental BLA for the new indication by the middle of next year.
Cell Genesys terminated VITAL-2, the second of two phase 3 trials of its GVAX prostate cancer vaccine, after revealing that 67 patients who received a combination of GVAX and docetaxel chemotherapy died, compared to 47 who were given docetaxel alone. Cell Genesys ended development of the program and laid off most of its employees.
| SELECTED FDA BIOLOGIC DRUG APPROVALS, AUGUST–SEPTEMBER 2008 | ||||
|---|---|---|---|---|
| Action date | Manufacturer | Drug (trade name) | Indication | Administration |
| Biologics license approval | ||||
| Aug. 22, 2008 | Amgen | romiplostim (Nplate) | Patients with ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy | Subcutaneous injection |
| New indication | ||||
| Sept. 12, 2008 | Talecris Biotherapeutics | IGIV (human), 10% (Gamunex) | CIDP | Intravenous infusion |
| SELECTED FDA ACTIONS, AUGUST–SEPTEMBER 2008 | ||||
| Manufacturer | Drug (trade name) | Type of drug | Indication sought | Notes |
| Biologics license application (BLA) | ||||
| GTC Biotherapeutics | ATIII (ATryn) | Recombinant antithrombin | Hereditary antithrombin deficiency | BLA filed Aug. 7; accepted Oct. 6;* priority review granted |
| Dyax | ecallantide, formerly DX-88 | Selective plasma kallikrein inhibitor | Hereditary angioedema | BLA filed Sept. 24 |
| Fast-track designation | ||||
| Proteon Therapeutics | PRT-201 | Recombinant human elastase | Improve vascular access for hemodialysis | Granted Sept. 10 |
| Orphan drug designation | ||||
| Stromedix | STX-100 | Humanized monoclonal antibody | Chronic allograft nephropathy | Granted Aug. 12 |
| Vivendy Therapeutics | enzyme replacement therapy | Recombinant human enzym | Morbus morquio | Granted Sept. 17 |
| Denials or delays | ||||
| Roche | tocilizumab (Actemra) | IL-6 receptor-inhibitor | Rheumatoid arthritis | Approval delayed, FDA seeks manufacturing information |
| Introgen Therapeutics | Ad5CMV-p53 (Advexin) | p53 tumor suppressor (gene therapy) | Recurrent, refractory head and neck cancer | “Complete response” letter issued Sept. 2 |
Ovation Pharmaceuticals acquired the license for commercialization of ATryn from GTC on Aug. 14. CIDP=chronic inflammatory demyelinating polyneuropathy, IGIV=immune globulin (intravenous), IL=interleukin, ITP=chronic immune thrombocytopenic purpura.
Sources: FDA, manufacturers’ news releases and package inserts, U.S. Securities and Exchange Commission filings
FDA actions
The FDA has begun a new system for responding to new drug applications. Instead of the former “approvable” and “not approvable” letters, the agency now issues “complete response” letters. Complete response letters communicate what manufacturers need to do to achieve approval. The FDA says this provides more consistent responses to manufacturers, but investors say it gives less insight into a drug’s prospects for approval. Only the company that receives a letter can disclose its contents — and decide how to frame the information.
Using power Congress granted it last year, the FDA called for new uniform boxed warnings about histoplasmosis and other fungal infections on the labels of four TNF-α blockers: infliximab (Remicade), adalimumab (Humira), certolizumab (Cimzia), and etanercept. The FDA reviewed 240 reported cases of histoplasmosis in patients taking the drugs. Of those, 45 people died and 21 cases were not promptly diagnosed, leading to delayed treatment. The FDA urges physicians to take precautions when prescribing TNF-α blockers to patients vulnerable to fungal infections.
Did you hear?
Two multiple sclerosis patients in Europe taking natalizumab (Tysabri) contracted progressive multifocal leukoencephalopathy —the first cases of PML since the drug’s reintroduction. Natalizumab, which was originally developed as an MS drug and has since has received an FDA indication for Crohn’s disease, is now under study in patients with multiple myeloma.