Maxim Pharmaceuticals Inc. initiated a Phase III trial with Ceplene and interleukin-2, this time using only patients who have advanced metastatic melanoma with liver metastases, and said it expects the trial coupled with previous data to be enough to support U.S. approval.
“We are pleased to get the trial under way. We’ve completed four clinical trials in metastatic melanoma already,” said Dale Sander, chief financial officer at Maxim. “We are looking forward to completing what we believe will be the last step to supporting approval in the United States.”
The M104 Phase III trial will be conducted at 25 sites in the U.S., Europe and Canada, and will involve 224 patients. In the M01 Phase III trial that ended in 2000, patients with metastatic melanoma and liver metastases (129 out of 305 patients enrolled) showed the greatest statistically significant benefit, and thus the new trial focuses on that group. The M104 trial has the same endpoint duration of patient survival and the “exact same treatment protocol as before,” Sander said, the only difference being the concentrated patient group.
Maxim, of San Diego, was seeking approval for the patient population with liver metastases when the Oncology Drug Advisory Committee shot down Maxamine, as it was then called, in December 2000 by a 14-to-0 vote. The company regrouped, re-analyzed, gathered 24-month data and renamed the drug Ceplene. Now, with the Phase III trial using solely the intended patient population, the company stands poised to make another run at U.S. approval, although trial results remain some time away. (See BioWorld Today, Dec. 14, 2000, and Oct. 23, 2001.)
“We’ve estimated conservatively it should take three years,” Sander said. “So we’ve allotted 18 months for enrollment and 18 months for followup.”
Sander said the FDA has indicated that the trial, if conducted in accordance with the approved protocol, should have the needed teeth to support filing.
“Certainly the guidance coming out of the FDA today is adequate and well-controlled clinical studies, and we’ve completed one already,” he told BioWorld Today. “This will be the second one of that it’s designed to be the second adequate, well-controlled study.”
The M01 trial showed that two-year survival rates for the 305 patients on an intent-to-treat basis were 18 percent for patients administered the combination of Ceplene and interleukin-2, and 10 percent for patients treated with IL-2 alone. But in the subpopulation, those figures improved.
“In the prior study, it suggested a two-year survival rate of 18 percent with Ceplene and the IL-2 combination, but 3 percent for patients that received IL-2 alone,” Sander said.
Ceplene is based on the naturally occurring molecule histamine. It is designed to prevent the production and release of oxygen free radicals. By preventing their production, Ceplene may protect the NK, T- and liver-type NK/T cells. Research has suggested that the immune system’s ability to destroy cancer or virally infected cells is suppressed by oxygen free radicals.
Maxim is working Ceplene hard. It also has the product in acute myelogenous leukemia Phase III trials and Phase II trials in renal cell carcinoma. Hepatitis C Phase II studies also are under way, and Sander said the company expected to start pilot studies in alcohol liver disease and nonalcoholic steato hepatitis. Overall, more than 1,300 patients have been involved in Ceplene clinical trials.
Maxim’s stock (NASDAQ:MAXM) rose 23 cents Thursday to close at $6.35.