First Chink in Nexavar's Armour as Bayer's Phase III Endpoints Not Met

German pharma heavyweight Bayer AG and development partner Onyx Pharmaceuticals (U.S.) have reported disappointing news for their oncology pipeline star, Nexavar (sorafenib). A press release issued by the two firms says that late-stage clinical trials on Nexavar failed to achieve the primary endpoint of improving progression-free survival (PFS) in patients with advanced melanoma. The international, double-blind, randomised, placebo-controlled Phase III trial was carried out on some 270 advanced melanoma patients who had undergone one prior systemic chemotherapy treatment with either dacarbazine (DTIC) or temozolomide. The trial combined Nexavar with chemotherapeutic agents carboplatin and paclitaxel in a standard 21-day dosing cycle. However, while the main objective of the study was to improve PFS while measuring the safety and efficacy of the drug, the primary endpoint of improving PFS could not be achieved. Complete data from the trial will be presented at an upcoming scientific congress.

Onyx has said that, while it is disappointed with the results, it intends to maintain its collaboration with Bayer over Nexavar, and intends to carry out more clinical trials on the drug in a wider variety of tumour settings, including tumours that are more common than advanced melanoma.

What neither company has mentioned, but will both be acutely aware of, is the Phase III disappointment's impact on Nexavar's race for market share with competitor product Sutent (sunitinib malate). Sutent, manufactured by U.S. pharma giant Pfizer, is already approved as a treatment for advanced renal cell carcinoma, as is Nexavar. The Pfizer drug was also approved by the U.S. Food and Drug Administration (FDA) as a treatment for gastrointestinal stromal tumours (GIST, a rare stomach cancer) in January this year, whereas Nexavar is not approved in this indication (see United States: 27 January 2006: Sutent Approval Heralds New Direction for Pfizer, but No Pricing Premium over Nexavar). Meanwhile, however, Nexavar was being developed as a treatment for advanced melanoma, and while Sutent is also being tested for melanoma, Nexavar was until recently held to be at a more advanced stage of the development process.

Outlook and Implications

Sutent may now hold a competitive advantage over Nexavar in terms of its development as a melanoma treatment, while another Pfizer drug candidate, CP-675,206 or ticilimumab, is currently in Phase III trials in a malignant melanoma setting. Bayer is holding one final card close to its chest, however, with both the FDA and the European Commission having noted the promise of Nexavar as a treatment for hepatocellular carcinoma (liver cancer; see Germany: 14 June 2006: FDA Awards Fast-Track Status to Bayer's Nexavar for Liver Cancer Indication and Germany: 19 April 2006: Bayer's Nexavar Clinches Orphan-Drug Status for Second Indication after Nod from European Commission). The liver-cancer trials are at the Phase III stage, and patient enrolment has just been completed. Meanwhile, a further Phase III trial on Nexavar in combination with carboplatin and paclitaxel as a treatment for treatment-naïve non-small-cell lung cancer (NSCLC) patients was launched in the first half of 2006. In this last setting, however, Nexavar will be faced with significant late-stage competition from the likes of Eli Lilly, Bristol-Myers Squibb and Genentech (all U.S.).

Bayer and Onyx have not confirmed officially whether they are abandoning the development of Nexavar as an advanced melanoma treatment, or whether they will relaunch Phase III trials. However, given the statement of Onyx Chairman, Hollings C. Renton, that "We will continue to broaden out clinical program, including increasing out attention to the more common malignancies in which anti-angiogenics have demonstrated activity", it appears that Bayer's hopes of a speedy second-indication approval for Nexavar will need to be shelved.