Novartis Malaria Combo Set For FDA Committee Review

Coartem will be milestone project for new priority review voucher incentive program.

Novartis' precedent-setting artemisinin combination therapy Coartem for malaria will go before FDA's Anti-Infective Drugs Advisory Committee Dec. 3, ahead of a year-end user fee date.

The Coartem (artemether/lumefantrine) application is commercially insignificant in its own right, but is likely to become the first to generate a priority review voucher under FDA's new incentive program to encourage development of drugs for neglected tropical diseases.

Novartis submitted an NDA for Coartem in acute uncomplicated malaria infection caused by Plasmodium jalciparum or mixed infections including P. jalciparum, in June. The application is receiving a priority review from the agency, setting a user fee action date in late December ("The Pink Sheet", Sept. 22, 2008, p. 26).

The advisory committee review is likely to include discussion of three interesting regulatory issues raised by the application: (1) It will be precedent setting for the new voucher incentive program; (2) It is a fixed-dose combination of two new molecular entities that are not already marketed here; and (3) Coartem's extensive use globally likely means it has one of the largest safety databases ever seen by FDA for a new molecular entity.

Coartem is approved in over 80 countries, including 16 in the European Union, with more than 200 million treatment courses administered. But it would be the first artemisinin combination therapy (ACT) approved in the U.S., the firm said.

"It is common for FDA to hold advisory committee hearings for new chemical entities, and Coartem contains two new chemical entities from an FDA review perspective," Novartis notes. FDA's regulatory process for combination therapies is not always easy to navigate, though it seems unlikely that the agency will let that become a significant issue in the context of the global health significance of the medication involved.

Under a new incentive program created by the 2007 FDA Amendments Act, companies that get approval for new drugs for neglected diseases are to be issued a voucher granting priority review status for another application (¹ (Also see "Biotech Sector Considers New Funding Vehicle: FDA Priority Review Voucher" - Pink Sheet, 15 Jul, 2008.)).

"While we have not discussed with FDA whether Coartem qualifies for the Priority Review Voucher, we assume it qualifies - if approved," Novartis said.

However, from a regulatory perspective, FDA and the advisory committee will have to look at the safety and efficacy in the context of the proposed U.S. indication-the roughly 3,000 cases of traveler's malaria diagnosed in this country each year.

Advocates for the neglected diseases incentive program will be watching closely to see whether the agency and its advisors are willing to allow the global public health role of the medicine to factor in their approach. The agency's decision to grant priority status to the application is already a signal that FDA will indeed take that approach.

Coartem is one of a number of combination therapies based on the ancient Chinese plant-based medicine artemisinin that have become more widely used for malaria due to resistance to older monotherapies.

The World Health Organization advises use of Coartem and three other ACTs as first-line therapies for malaria: artesunate-amodiaquine ( Coarsucam/ASAQ from Sanofi-Aventis); artesunate-mefloquine ( Mefonate from Adams Pharmaceutical); and artesunate/sulfadoxine-pyrimethamine ( Co-Arinate from Dafra Pharma).

The Novartis Institute for Tropical Diseases, a public-private partnership, is co-developing a pediatric formulation of Coartem with the Medicines for Malaria Venture, with plans to file for approval in at least one European country by the end of this year.

- Emily Hayes ([email protected])