US FDA 'Complete Response' letters delay Novartis and Roche/Biogen products

Swiss drug majors Novartis and Roche, the latter in conjunction with its partner Biogen Idec and US subsidiary Genentech, have received 'Complete Response' letters from the US Food and Drug Administration, delaying the regulatory process for two of their products.

Roche, Genentech and Biogen Idec received the communication with respect to their supplements Biologics License Application for Rituxan (rituximab) plus methotrexate (MTX) in patients with moderately-to-severely active rheumatoid arthritis (RA) who no longer respond to treatment with a disease modifying antirheumatic drug (DMARD), including MTX.

The FDA has indicated that it does not believe an approval for Rituxan as first-line treatment (in people with RA who have not previously received MTX or those who were MTX inadequate responders) can be supported at this time due to the rare risk of progressive multifocal leukeoencephalopathy (PML) in light of the number of effective RA treatments currently available to patients in earlier stages of the disease. Rituxan, known outside the USA as MabThera, in its current indications for non-Hodgkin's lymphoma, chronic lymphocytic leukemia and RA generated sales of 4.6 billion francs ($4.5 billion), in the first nine months of this year (The Pharma Letter October 15).

However, the FDA approved a label expansion to use Rituxan as a retreatment option in patients who had an inadequate response to current standard treatment. "Overall we could have increased our Rituxan RA numbers by about $300 million for the longer treatment duration. However, we would need to reduce our expectations for Rituxan in the earlier setting by $300 million," said Vontobel analyst Andrew Weiss.quoted by Forbes magazine. "Hence the impact of the two announcements should be neutral," he noted.

Roche stock rose 0.8% to 163.60 Swiss francs by 0902 GMT, just ahead of a 0.5% rise in the DJ Stoxx European healthcare index.

Dosing data wanted for QAB149

For its part, Novartis received a Complete Response letter for QAB149, also dubbed indacaterol, for the treatment of chronic obstructive pulmonary disease (COPD). The FDA has requested additional information on the dosing proposed for QAB149. Novartis says it will work with the agency to review already submitted data for the drug, as well as recently available data to determine what, if any, further clinical trials would be required. QAB149 was filed for approval in the USA in December 2008.

"Our confidence in the benefit/risk profile of QAB149 is based on results of Phase III trials which showed QAB149 significantly improved lung function," says Trevor Mundel, global head of development at Novartis Pharma.

QAB149 is the first once-daily bronchodilator treatment and the European Medicines Agency (EMEA) has backed approval of the drug, a recommendation which is likely to be followed by the European Commission.