Pfizer Halts Lung Cancer Trials Of Toll-Like Receptor Agent
This article was originally published in The Pink Sheet Daily
Executive Summary
Fate of other oncology trials of the TLR9 candidate Pfizer licensed from Coley has not been made public.
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Pfizer halted four mid- to late-stage trials of a Toll-like receptor 9 candidate in non-small cell lung cancer after an interim analysis showed the TLR9 agonist paired with chemotherapy demonstrated no clinical efficacy over standard chemo alone, the company announced June 20. The drug maker said it pulled the plug on two Phase III and two Phase II trials on advice of a data safety monitoring board after its interim analysis of data from both Phase III trials concluded "the risk-benefit profile did not justify continuation of the trials." It was unclear whether Pfizer will cease all development of the TLR, PF-3512676, which it licensed from Wellesley, Mass.-based Coley Pharmaceutical Group in a 2005 deal worth $505 million. "We don't yet know what this will mean in the long term for '676," Coley CEO Robert Bratzler said in a same-day conference call. "For the TLR space as a whole, obviously this is a setback for this approach to the treatment of lung cancer in these combination regimens and chemotherapy." While Pfizer said it would halt two Phase II trials, three had begun dosing in lung cancer studies pairing '676 with targeted therapies. Bratzler said Pfizer has not disclosed which two of the three trials it closed. According to analysts on the call, the drug maker was testing '676 in combination with Lilly's Alimta (pemetrexed), Genentech/OSI's Tarceva (erlotinib) and Genentech's Avastin (bevacizumab) to see if the immune enhancing agent can enhance their tumor-killing effects. In addition, the fate of a planned study of '676 in combination with an experimental mAb as a therapy for melanoma has "not been decided or disclosed," Bratzler said. The fate of a study of '676 in breast cancer that was set to begin enrollment in August is similarly unknown, he said. In a separate blow to its development pipeline, Pfizer also announced June 20 that it had received an "approvable" letter from FDA on its potential first-in-class CCR5 co-receptor antagonist for AIDS, maraviroc (see 1 (Also see "Pfizer’s Maraviroc Deemed “Approvable” By FDA" - Pink Sheet, 21 Jun, 2007.)). A day later, the firm saw positive news when its Neurontin follow-on Lyrica (pregabalin) became the first drug cleared for treatment of fibromyalgia (see 2 (Also see "Pfizer’s Lyrica Is First Drug Approved For Fibromyalgia" - Pink Sheet, 21 Jun, 2007.)). Coley has a dominant position in the Toll-like receptor space, having nearly doubled its TLR patent estate earlier in June with the purchase of 3M's program (3 (Also see "Coley Doubles Toll-Like Receptor Patent Estate With Purchase Of 3M Program" - Pink Sheet, 12 Jun, 2007.)). TLRs are a new class of drug candidates that direct the immune system to fight cancers, allergy and asthma disorders and act as adjuvants to enhance the effectiveness of vaccines, according to Coley. Another TLR-focused company, Idera Pharmaceuticals, in Cambridge, Mass., is also investigating its experimental TLR9 agonist in combination with oncologics. In April, the firm reported that its candidate, IMO-2055, demonstrated "additive antitumor activity with sorafenib" (Bayer/Onyx's Nexavar ) in a mouse model. Idera has a licensing deal with Merck for agonists targeting TLR7, 8 and 9 for a variety of therapeutic areas, including vaccines (4 (Also see "Merck To Incorporate Idera’s TLR Agonists Into Vaccine Program" - Pink Sheet, 11 Dec, 2006.)). - Shirley Haley ([email protected]) |