Washington Editor

Medarex Inc. is pushing its targeted cancer therapy, ipilimumab, into a registrational trial for untreated metastatic melanoma patients after receiving a special protocol assessment from the FDA.

If successful, the study would support an approval as a first-line treatment; already, it is in Phase III testing as a second-line therapy for metastatic melanoma, and a regulatory filing is expected next year for that initial indication. The fully human antibody, also known as MDX-010, represents the nearest-term commercial opportunity for Princeton, N.J.-based Medarex.

"This is part of a multi-pronged strategy," President and CEO Donald Drakeman told BioWorld Today, noting that because the earliest data came from second-line patients, it made sense to continue forward in that path first. "Then, as the data matured on front-line treatment, we saw that it also represented a good registration opportunity, so we've gone ahead with this trial."

Ipilimumab is targeted against human CTLA-4, an "important" molecule on T cells, Drakeman said. It is believed to be responsible for suppressing the immune response, so Medarex and partner Bristol-Myers Squibb Co. are investigating the drug's potential to enable cancer patients' immune systems to help suppress or eradicate the tumor.

Because it "enhances and amplifies" that immune response to the tumor, Drakeman said that it "can be used in many different cancers." He labeled melanoma "the entry point" for ipilimumab, noting that there is a growing body of evidence supporting the drug's use in that patient population, which "desperately needs new treatments."

The new study, which is set to begin soon in multiple countries, will test ipilimumab's use in combination with chemotherapy. The double-blind trial will randomize about 500 patients into two different arms. One group will receive 10 mg/kg of ipilimumab in combination with dacarbazine, and the other will receive dacarbazine alone. Administrations are to be given once every three weeks for up to four doses. Subsequently, eligible patients who have not experienced disease progression at week 24 will continue in a maintenance phase in which a single dose of ipilimumab will be administered once every 12 weeks until disease progression.

Drakeman declined to forecast the trial's duration.

Progression-free survival is its primary endpoint, but secondary endpoints include overall survival, progression-free survival rate at week 12, best overall objective response rate and duration of responses, as well as the disease control rate, defined as complete and partial responses plus stable disease.

Terms of Medarex's partnership with Bristol-Myers Squibb call for the New York-based pharmaceutical firm to foot about two-thirds of the bill for the study and others, with Medarex picking up the remainder. The trials are designed jointly, and other responsibilities for running the studies are shared between the partners.

Looking ahead, Medarex has an option to co-promote ipilimumab in the U.S., where the company would receive 45 percent of profits. Bristol-Myers Squibb would get the rest and pay an undisclosed royalty back to Medarex on overseas sales. The company received an initial $50 million payment and could earn up to $480 million in regulatory and sales milestones. (See BioWorld Today, Nov. 9, 2004.)

Other ongoing work on ipilimumab includes a recently initiated monotherapy study for metastatic melanoma, which is expected to complete enrollment this year. An open-label, single-arm trial, it will involve about 150 patients. Another combination study is testing its use with MDX-1379, a melanoma peptide vaccine, in 750 patients. Both are registrational trials as second-line therapy under two separate special protocol assessment agreements. (See BioWorld Today, Aug. 24, 2004, and April 3, 2006.)

Ipilimumab also is in multiple Phase II trials to investigate its activity in other tumor types, such as ovarian, renal and prostate cancers, as well as lymphoma and leukemia. "And we're looking at a wide range of others," Drakeman said, noting that the potential exists to use the product in every tumor. The partners have not yet indicated which indication they would next pursue for approval, "but we have seen very promising data in a number of areas," he added.

"It's not just targeting a tumor molecule, it's targeting a molecule that basically turns the immune system off," Drakeman said. "By blocking that molecule, we can have the immune system much more active and effective in fighting the cancer.

On Monday, shares in Medarex (NASDAQ:MEDX) dropped 32 cents to close at $9.20.