Genasense Trial Results Raise Questions About Efficacy for Advanced Melanoma Treatment

Strategic Insights -

Genasense, an experimental cancer treatment, showed mixed results in a Phase 3 trial for advanced melanoma patients. While it improved progression-free survival and response rates, it failed to demonstrate increased overall survival. The Oncologic Drugs Advisory Committee (ODAC) of the FDA voted that the evidence did not provide substantial evidence of effectiveness to outweigh the increased toxicity of administering Genasense.

The largest randomized trial ever conducted for advanced melanoma enrolled 1,131 patients across nine countries, with 771 receiving Genasense plus dacarbazine and 360 receiving dacarbazine alone. The trial showed a 51% improvement in median progression-free survival (74 days vs. 49 days), a 22% increase in durable response rate (13 patients vs. 5 patients), and a 72% increase in overall anti-tumor response rate (11.7% vs. 6.8%). However, the treatment also increased the risk of adverse events, including fever, neutropenia, thrombocytopenia, leukopenia, anemia, and nausea.

Genta Incorporated, the developer of Genasense, will work closely with the FDA to determine the next course of action. The FDA is expected to make a decision on the New Drug Application (NDA) for Genasense by June 8, 2004.

Key Takeaways:

  • The trial demonstrated improved progression-free survival, durable response rate, and overall anti-tumor response rate in advanced melanoma patients receiving Genasense plus dacarbazine.
  • The treatment also increased the risk of adverse events, including fever, neutropenia, thrombocytopenia, leukopenia, anemia, and nausea.
  • The FDA's ODAC voted that the evidence did not provide substantial evidence of effectiveness to outweigh the increased toxicity of Genasense.
  • Genasense inhibits Bcl-2 protein production, which is thought to block chemotherapy-induced apoptosis.
  • Genta is pursuing a clinical development program with Genasense to evaluate its potential in treating various forms of cancer.

Statistics:

  • 51% improvement in median progression-free survival with Genasense plus dacarbazine (74 days vs. 49 days)
  • 22% increase in durable response rate with Genasense plus dacarbazine (13 patients vs. 5 patients)
  • 72% increase in overall anti-tumor response rate with Genasense plus dacarbazine (11.7% vs. 6.8%)
  • 771 patients received Genasense plus dacarbazine in the Phase 3 trial
  • 360 patients received dacarbazine alone in the Phase 3 trial
  • 139 sites in nine countries were involved in the Phase 3 trial
  • 55,000 cases of melanoma will be diagnosed in the U.S. in 2004 (American Cancer Society estimate)
  • 132,000 melanoma skin cancers will occur globally every year (World Health Organization estimate)

Sources:

  • Genta Incorporated press release
  • Aventis press release
  • American Cancer Society website
  • World Health Organization website