By Kim Coghill
BETHESDA, Md. ¿ A negative vote by a government panel Monday likely will hurt Matrix Pharmaceutical Inc.¿s chances of getting its cancer gel on the market.
In a unanimous vote, the Oncologic Drugs Advisory Committee (ODAC) said Matrix¿s data fail to provide substantial evidence that IntraDose Injectable Gel is safe and effective. And in a 9-to-3 vote, with one member abstaining, the panel said the response rate of patients in the trials was not beneficial. The vote was the same when considering whether IntraDose should be granted accelerated approval.
The FDA will make the final decision, and typically follows the committee¿s recommendation.
IntraDose (cisplatin/epinephrine) was developed to treat patients with head and neck cancer who have few, if any, remaining treatment options. The company filed the NDA in January and was granted fast-track and orphan status. Treatment options currently available are surgery, chemotherapy or radiation.
IntraDose is injected directly into tumors with the goal of achieving high, sustained, intratumoral cisplatin concentrations for extended periods of time, but without the toxicities typically seen with systemically administered cisplatin, the company said.
However, George Sledge, a panel member and professor in the Department of Medicine and Pathology at the Indiana University School of Medicine in Indianapolis, said the data show IntraDose appears to produce systemic side effects that include pain. The company argued that the side effects are local, temporary and generally associated with the injection. Also, some patients have experienced nausea and vomiting, but not to the extent that is experienced by chemotherapy patients.
Matrix presented data on its two pivotal Phase III studies totaling 178 patients. Both were prospective, randomized, double-blind, placebo-controlled studies that compared the safety and efficacy of IntraDose to placebo in patients with recurrent or refractory tumors. Patients were required to have received at least one prior therapy.
In its submission to the FDA, the company said the tumor response in patients with advanced disease was clinically meaningful.
¿It is remarkable what the sponsor was able to do,¿ said Scott Lippman, a panel member and professor of medicine and cancer prevention at the University of Texas in Houston. ¿These are very difficult trials to conduct and I would like to see a larger trial.¿
Rajeshwari Sridhara, an FDA reviewer, disagreed that the trials were statistically significant, saying patients on active dose did not benefit or respond to treatment. IntraDose appears to shrink tumors 25 percent to 30 percent of the time, according to the FDA.
The FDA also presented data showing errors and deviations that could impact the integrity of the trials. Frykman told ODAC that there were errors in measurement, calculation and administration of dosing, though more patients were underdosed than overdosed.
Glenn Mills, who conducted IntraDose trials and spoke on behalf of the company, said each year there are about 50,000 or so new patients diagnosed with head and neck cancer, and of those individuals, about 15,000 die each year. Mills is the director of the head and neck program at Louisiana State University in Shreveport.
Despite the FDA¿s less-than-positive review of IntraDose, others highlighted the benefits of the gel.
Richard Curry told the panel that his father was one of those patients whose quality of life was diminished by current therapies. Eventually his father ended up participating in a clinical trial of IntraDose, and Curry said, ¿If IntraDose had been available when my father was diagnosed, I believed it would have improved his quality of life.¿
Curry said after his father began participating in the trial, he was able to resume certain physical activities like golf and fishing.
And Edward McCartan, a cancer survivor, told ODAC the current treatment options are limited and generally associated with serious side effects, some temporary, like the loss of hair, but others more permanent, like the ability to talk or taste. ¿There are many cancer survivors who have told me if they had known about the side effects of [traditional therapies] they would not have opted to take treatment.¿
Matrix, of Fremont, Calif., also is testing IntraDose on other indications including liver cancers, metastatic breast cancer, esophageal cancer and malignant melanoma. Aside from IntraDose, Matrix also is testing tezacitabine, a next-generation nucleoside analog for systemic treatment.
Trading on Matrix¿s stock (NASDAQ:MATX) was held Monday, as it was Friday when FDA review documents were made public, at $6.79.