Hana Braces For Additional Zensana Research

Problem discovered in commercialization ramp-up of the antiemetic spray has company anticipating additional studies, more FDA review time.

Hana Biosciences may have to delay a planned 2007 launch of Zensana , its oral spray formulation of ondansetron, after precipitate was discovered in some scale-up batches of the antiemetic during regular testing, Chief Executive Officer Mark Ahn said during a Feb. 20 conference call.

Ahn said the company has "about a dozen" experiments ongoing to determine why batches of the oral spray stored below room temperature had the material in them. The company does know enough to know that "while it's precipitating, the drug is not degrading," a potentially more serious problem, Ahn said.

"There are two ways that we could make changes," he said. The first would involve changes based on the solvent system or with the flavor masking or taste flavoring, and the second is the "more obvious route, where we are too near the saturation point, and we need to dilute down the formula."

"Whether both or one of those would cause us to need to have more clinical trials is really subject to review and some guidance ... from FDA." Major formulation changes and changes to active ingredients likely would require new clinical trials, and the changes of simple taste enhancers or masking agents probably would not, he said.

"We should count on the conservative case that we'll have to do a 32-patient bioequivalency study, establish equivalence to an 8 mg tablet, and then move on from there," Ahn said, adding that Hana could "get through" such a study and "have the report inside of a quarter."

Zensana is still worth the investment, Chief Business Officer Fred Vitale said. "If you look ahead to the 2008 market - and let's just assume if we had to go that far down the road in terms of commercialization - clearly there are going to be more generics in the marketplace, price pressures will be down, but I think you'll still find that there's not going to be any spray form of 5-HT3 [antagonist] that's available ... to meet the unmet needs of patients who have difficulty swallowing," Vitale said.

The South San Francisco, Calif., company is asking approval of Zensana for prevention of nausea and vomiting associated with chemotherapy, radiotherapy, and postoperative induced nausea and vomiting. It has an April 30 user fee date, though Hana noted it anticipates an extension.

The company announced in June that it had submitted the Zensana NDA under the 505(b)(2) pathway (¹ (Also see "Ondansetron Oral Spray Could Launch In H1 07" - Pink Sheet, 3 Jul, 2006.)). Zensana would be the first spray formulation of ondansetron (GlaxoSmithKline's Zofran and generics).

Ahn said he would update analysts during the company's March 20 earnings call.

In January, FDA granted Hana's lead oncology candidate Marqibo (liposomal vincristine) an orphan drug designation for acute lymphoblastic leukemia. The company plans two clinical trials for Marqibo, one a 56-patient supporting trial and the other a 120-patient Phase II pivotal trial to be conducted under a special protocol assessment.

Ahn said the company expected to hear from FDA "as we speak" on the SPA for the pivotal trial and plans to launch the study in the second quarter. "The agency has agreed on an accelerated approval on the basis of the two trials proposed, the supportive trial and the pivotal trial, and we're now seeking agreement on ... elements of the protocol," Ahn said.

A Phase III trial, to be conducted by the cooperative groups, should begin enrollment by the end of the year and will serve as the basis for full approval of the drug, Hana said.

Hana licensed Marqibo from Inex Pharmaceuticals in March 2006. In January 2005, Inex received a "not approvable" letter on its NDA for Marqibo based on a single-arm Phase II trial (² (Also see "Inex/Enzon's Marqibo Accelerated Approval Application "Not Approvable"" - Pink Sheet, 19 Jan, 2005.)).

- Shirley Haley ([email protected])