Following the FDA's request last week for more data on its Xolair anti-IgE antibody for allergic asthma, Genentech Inc. must be weighing the pros and cons of continuing to throw money at the product.

DNA, which has been moving out of the pulmonary market, could decide there is little benefit to doing more trials as the timeline for approval recedes into the future and the indication narrows. On the other hand, a high-priced drug addressing even a small slice of the asthma market could provide consequential revenues.

According to physicians, the compound's best bet is if it can be shown to reverse airway remodeling in asthma patients. If it can't, Xolair rhuMAb-E25 would face a highly competitive marketplace of inexpensive steroids and bronchodilators. In that case, they expect its use to be reserved for the most severe asthma patients.

Narrower indication

The FDA last week sent DNA (South San Francisco, Calif.) and partner Novartis AG (NVS; SWX:NOVN, Basel, Switzerland) a complete response letter asking for additional preclinical, clinical and pharmacokinetic data for their BLA. As a result of these requests, the companies said they will narrow the proposed indication for Xolair to moderate to severe adult asthma. The original BLA filing was for asthma and seasonal allergic rhinitis in both adult and pediatric patients. The therapy is to be used as an adjunct with other treatments.

According to DNA, the agency "is looking for more patient experience on the drug." NVS told BioCentury that the FDA is concerned with "primarily theoretical risks of uncommon events and whether the safety data is robust enough to rule out such theoretical risks."

Because of the letter, the companies said FDA approval of the Xolair rhuMAb-E25 will not take place in 2001 and there also will be a delay in European approval since they will submit the new data to the EMEA as well. The companies now expect to resubmit their BLA in 2002 or early 2003, which would push potential approval out to 2004. DNA told BioCentury that a meeting with the FDA within the next month "would give a better idea on the timeline."

The companies said they believe that substantial information can be provided from completed trials and ongoing trials such as the 900-patient ALTO trial, an open-label Phase IIIb study assessing the overall safety of Xolair in moderate to severe asthma patients already treated with other therapies. However, they said additional trials may be necessary in specific subgroups. In particular, NVS said the agency has asked for safety data from pediatric and geriatric groups, non-caucasians, patients given oral corticosteroids, and patients with a history of hospitalization for asthma.

In the meantime, according to DNA, the partners have decided to focus on a narrower indication in adult allergic asthmatics "to get approved of the product in an expedited fashion."