Members of the FDA's Pulmonary-Allergy Drugs Advisory Committee (adcom) voiced majority support on Wednesday for the approval of Teva Pharmaceutical Industries Ltd.'s Cinqair (reslizumab) injection for adults with asthma, though they stood firmly against potential use of the drug in children, 12 to 17 years.

Teva is seeking approval for the interleukin-5 antagonist to complement its existing portfolio by adding to its existing asthma portfolio of inhaled therapies a product for severe patients that could potentially reduce exacerbations, relieve symptoms, and improve lung function for patients with asthma and elevated blood eosinophils who are inadequately controlled on inhaled corticosteroids. (See BioWorld Today, June 16, 2015.)

Following a session of animated discussions poking and prodding Teva's clinical data, adcom members ultimately voted 11-3 in favor of the available efficacy and safety data supporting FDA approval of Cinqair 3 mg/kg IV every four weeks for the treatment of adult patients with asthma. A vote on the same question, but for pediatric patients, came down against recommending approval for that group, with panelists voting 14-0.

Separate votes on other questions yielded marginally different results, with panelists voting 13-1 in favor of the efficacy data providing substantial evidence of a clinically meaningful benefit of reslizumab for the treatment of asthma and again 14-0 opposing pediatric efficacy evidence. They also voted 11-3 in support of the drug's safety profile being adequate to support approval in general.

Data from four separate placebo-controlled trials involving more than 1,700 adult and adolescent asthma patients with elevated blood eosinophils and whose symptoms were inadequately controlled with inhaled corticosteroid (ICS)-based therapies were included in Teva's biologics license application. The studies demonstrated that reslizumab, in comparison to placebo, reduced asthma exacerbation rates by at least half and provided significant improvement in lung function and other secondary measures of asthma control when added to an existing ICS-based therapy.

On the efficacy front, FDA statistical reviewer Lan Zeng verified that Cinqair was successful in effectively reducing asthma exacerbation frequency and improving lung functions. However, the agency's clinical reviewer, Kathleen Donohue, expressed concerns about both anaphylaxis and muscle toxicity, saying that both had emerged as "important safety signals" in the Cinqair program. Given limitations in the clinical data, she said, adcom members were "faced with a bit more than the usual amount of uncertainty" in evaluating the therapy's overall safety while projecting a slide with the tip of a iceberg peeking above sea-level.

For every 1,000 patients a doctor treats with Cinqair for one year, Donohue said, they could be expected to prevent 182 asthma exacerbations and five asthma-related hospitalizations. However, they could also expect to manage three cases of anaphylaxis and 46 cases of CPK elevations.

FDA reviewers also expressed concern over Teva's dose-ranging study 3081, which was conducted in parallel with the exacerbation studies, 3082 and 3083, meaning that results from study 3081 could not inform either dose or patient selection in 3082 or 3083, noted Thomson Reuters Cortellis Clinical Trials Intelligence. With limited dose-ranging data, it was left unclear whether a lower dose might have also been effective as the 3 mg/kg dose.

The limited amount of pediatric efficacy data Teva provided also drew virtually unanimous concern from both FDA reviewers and adcom members, with one, University of Colorado associate professor Elaine Morrato, saying that she felt the efficacy data on 19 children was "not much more than in a qualitative study, and we just don't approve drugs based on qualitative data and case series."

Like Glaxosmithkline plc's Nucala (mepolizumab), approved Nov. 4, Cinqair targets IL-5, a key protein involved in the maturation, recruitment and activation of eosinophils, which are implicated in a number of diseases, such as asthma. Because elevated levels of blood eosinophils are a risk factor for future asthma exacerbations, Cinqair binds circulating IL-5, thus minimizing the production of eosinophils and preventing it from binding to its receptor. (See BioWorld Today, Nov. 6, 2015.)

Despite those reservations, most panelists in the end seemed to share the view of another adcom member, Steve Georas, a professor of medicine at the University of Rochester: From the 10,000-foot view, he said, "I think this compound does address an unmet need in severe asthma. The reduction in exacerbations and symptom improvement at the 3 mg dose I find compelling."

Teva shares (NYSE:TEVA), which declined toward the midpoint of the discussion, recovered most ground lost during the day to close at at $65.46 on Wednesday, just 21 cents off Tuesday's close.