Washington Editor

WASHINGTON - The FDA's oncology advisory committee is meeting today to form an opinion on two cancer drugs, clofarabine and Marqibo, and a review of the latter could prove dicey based on a briefing document made public by the agency Tuesday.

On its website, the FDA posted comments by its review team questioning whether data from a clinical study underlying Marqibo's new drug application, filed by Inex Pharmaceuticals Corp., meets requirements for accelerated approval. The company submitted an international, multicenter, single-arm Phase II study of patients with relapsed aggressive non-Hodgkin's lymphoma for such an approval based on response rate. But the submitted data were from only 65 patients whom the FDA found to be evaluable for an accelerated approval claim. That is equal to 54.6 percent of the total study population.

The trial originally enrolled 119 patients, but the company amended the protocol nine times, including the eligibility criteria, and granted exemptions that allowed patients who otherwise would not be enrolled.

In the briefing document, the review team noted concerns about the exemptions, how the study was conducted, the independent response panel process and adjudication, revision of standardized criteria that prevented comparison to historical controls, and the magnitude of responses.

The agency also noted that in the evaluable study population, the unconfirmed response rate (made up of complete responses, partial responses and unconfirmed complete responses) was 21.5 percent. The confirmed response rate was 12.3 percent. The study response rates consist mostly of partial responses of short duration, the FDA added.

The agency, which plans to complete its review of the NDA by Jan. 15, added that it has discussed Phase III study designs with Inex, a common pr ocess for any product under an accelerated approval path. Protocol finalization is under way.

The Vancouver, British Columbia-based company began submitting a rolling NDA a little more than a year ago. (See BioWorld Today, Oct. 1, 2004.)

Formerly called Onco TCS, the drug is made of an off-patent cancer drug, vincristine, encapsulated in Inex's sphingosomal drug delivery technology. Inex and its partner, Enzon Pharmaceuticals Inc., of Bridgewater, N.J., both declined to comment on the briefing document.

The companies entered their agreement earlier this year in a deal valued at about $75million for Inex. Outside of seeking approval in non-Hodgkin's lymphoma, the partners continue to explore Marqibo's use as a single-agent therapy or in combination therapy for several cancers in which vincristine is used. (See BioWorld Today, Jan. 21, 2004.)

Inex requested that trading of its stock on the Toronto Stock Exchange be halted Tuesday and kept frozen until after the Oncologic Drugs Advisory Committee meeting today. The request was granted, as its shares (TSE:IEX) remained at C$5.45 (US$4.59) Tuesday. Shares in Enzon (NASDAQ:ENZN) fell 18 cents to close at $13.54.

The other drug scheduled for review during today's committee meeting, clofarabine, has been developed in the U.S. by ILEX Oncology Inc. It has proposed Clolar as its trade name.

The San Antonio-based company, the subject of a $1 billion buyout by Genzyme Corp., earlier this year completed its new drug application for the product in the treatment of refractory or relapsed acute leukemia in children. Pivotal Phase II data, reported at last summer's American Society of Clinical Oncology meeting, showed an overall response rate of 29 percent for clofarabine in heavily pretreated children with acute myelogenous leukemia or acute lymphoblastic leukemia. ILEX submitted the first part of the rolling NDA a little more than a year ago. (See BioWorld Today, Oct. 23, 2003.)

Genzyme, of Cambridge, Mass., entered the deal to acquire ILEX largely because of the latter's cancer drug portfolio. In addition to clofarabine, ILEX has been earning revenue from sales of Campath (alemtuzumab for injection) for B-cell chronic lymphocytic leukemia. (See BioWorld Today, March 1, 2004.)

The FDA, which has been evaluating the clofarabine submission under priority review, also has named it an orphan drug for adult and pediatric acute lymphoblastic leukemia and acute myeloid leukemia. The next-generation purine nucleoside analogue is being investigated for use in both adult acute leukemias, as well as in advanced solid tumors. Clofarabine also has fast-track status.

ILEX licensed exclusive North American development, marketing and manufacturing rights for the product more than three years ago. The drug is being developed outside North America by Bioenvision Inc., of New York. (See BioWorld Today, March 16, 2001.)

Tuesday, ILEX's stock (NASDAQ:ILXO) lost 11 cents to close at $24.86. Genzyme's shares (NASDAQ:GENZ) rose 17 cents to close at $56.01.

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