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Kosan Biosciences: some hope for metastatic melanoma
Kosan Biosciences is to initiate a Phase II clinical trial of 17-AAG for metastatic melanoma.
July 20, 2004 6:32 PM GMT (Datamonitor) - The success of Kosan Biosciences' [KOSN] Phase II clinical trial, investigating 17-AAG for Stage III and IV metastatic melanoma patients who have failed one prior course of therapy, could be increased with the development of a diagnostic to determine B-Raf status of patients to be enrolled into the trial.
17-AAG (17-allylamino-17-demethoxy-geldanamycin) confers its mode of action by inhibiting heat shock protein 90 (Hsp90), a protein chaperone that binds to specific signaling proteins. These signaling proteins constitute several oncology-relevant targets including, among others, mutated p53, Bcr-Abl, HER-2, Raf-1 and B-Raf. By binding to Hsp90, 17-AAG disrupts the Hsp90-signaling protein complexes, thereby leading to degradation of relevant tumor cell targets.
Mutations in B-Raf are found in approximately two-thirds of melanoma patients. By enhancing degradation of this protein, researchers speculate that 17-AAG will effectively disrupt the tumor growth pathway. The Phase II clinical trial will administer 450mg/m2 of 17-AAG weekly for six weeks as part of an eight-week cycle. This will determine any measurable antitumor activity of the drug, as well as its pharmacodynamics and any effects on B-Raf.
Metastatic melanoma patients are poorly served by current therapeutics. Few approved agents exist for Stage III and IV patients, with a lack of consensus on what constitutes gold standard therapy. In addition, the most frequently used agents, interferon alpha-2b and dacarbazine, only induce a tumor response in up to 20% of patients.
Many agents in development for metastatic melanoma fail to show any benefit in clinical trials, most likely due to the highly resistant nature of the disease. If Kosan Biosciences can show some benefit over current therapeutics, it is likely that the uptake will be significant. However, 17-AAG has only just reached Phase II clinical trials, thus facing many more years of development before commercialization is possible.
Kosan Biosciences could increase the commercial potential of this opportunity by partnering with a specialist diagnostics company to develop a test to determine if B-Raf drives tumor growth in individual patients. By selecting patients for clinical trials based on B-Raf status, the likelihood of positive results, and ultimately approval, is increased. |
