Ganitumab disappoints in pancreatic cancer: Amgen halts Phase III Study

In a press release on August 8, 2012, Amgen announced that the company was halting a late-stage trial of its monoclonal antibody IGF-1 receptor antagonist ganitumab (AMG-479).

The 825-patient, Phase III GAMMA (Gemcitabine and AMG-479 in Metastatic Adenocarcinoma of the Pancreas) trial was investigating the combination of ganitumab and Eli Lilly’s Gemzar (gemcitabine) as a first-line treatment for patients with metastatic pancreatic cancer.

The company stopped the trial in response to a recommendation from an independent data monitoring committee (DMC). In a planned interim analysis, the DMC concluded that the ganitumab/Gemzar combination was unlikely to significantly improve the overall survival of patients compared to Gemzar monotherapy, GAMMA’s primary endpoint. Amgen also announced it would be stopping a separate Phase II trial investigating the use of ganitumab in locally advanced pancreatic cancer. The GAMMA trial was co-sponsored by Takeda, who has the right to develop and commercialize ganitumab in Japan through collaboration with Amgen.

The pancreatic cancer community will no doubt receive this news with great disappointment. Pancreatic cancer has a relatively low prevalence in the US; the American Cancer Society estimates 43,920 new cases will be diagnosed in 2012, compared to 226,870 new cases of breast cancer and 226,160 new cases of lung cancer. As a result, pancreatic cancer awareness is much lower than that of these other, more prevalent diseases. However, there is a gaping unmet need for the treatment of pancreatic cancer, as it is one of the most aggressive cancers, with low 5-year survival rates. According to the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, 53% of pancreatic cancers are metastatic at diagnosis and have a 5-year relative survival rate of 1.8%. Metastatic pancreatic cancer is incurable, and current treatment options are limited and include Gemzar, Roche/Genentech/Astellas’ Tarceva (erlotinib) and a combination of 5-fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFIRINOX).

Stopping the trial was a prudent decision by Amgen. It conserves valuable resources and allows Amgen to invest in more promising products in its deep pipeline, perhaps even towards the development of ganitumab for the treatment of other cancers. The company is currently sponsoring early-stage trials evaluating ganitumab for the treatment of small cell lung cancer, colorectal cancer and other solid tumors. Even if ganitumab were to somehow gain regulatory approval for pancreatic cancer, it would never be commercially successful as patients could get the same overall survival benefits by using Gemzar monotherapy. This is especially true in major markets like Germany, where in order for a drug to demand premium pricing it must show a clear clinical benefit over the current standard of care.

Ganitumab was one of the most promising pancreatic cancer drugs in late stages of development, and its recent clinical failure is a disappointment. However, no safety concerns were raised, so it is possible that ganitumab may be helpful in combination with a different drug or in treating a different segment of pancreatic cancer patients. Since patients with this disease have relatively few options, it might be worthwhile for Amgen to explore the use of ganitumab in patients with metastatic pancreatic cancer who have become refractory to Gemzar. In addition, Novartis is about to begin enrollment of a Phase II trial evaluating the combination of its developmental mitogen-activated ERK kinase inhibitor MEK162 in combination with ganitumab in patients with metastatic pancreatic cancer. If this trial is successful, it could present a partnering opportunity for Novartis and Amgen, and lead to a crucial advance in the standard of care for pancreatic cancer. The likelihood of Amgen exploring these opportunities will increase if ganitumab proves to be effective in additional indications.

*Ganitumab Disappoints in Pancreatic Cancer: Amgen Halts Phase III Study