Biotech Values

[DewDiligence]

NVS’ NVA237 Succeeds in ‘GLOW2’ Phase-3 Study in COPD

[NVA237 is a long-acting muscarinic antagonist (LAMA) that NVS is developing as a monotherapy for COPD and as a combination therapy with QAB149 (a LABA) for asthma and COPD. As a monotherapy, NVA237 has now succeeded in two large phase-3 trials: GLOW-2, the subject of this PR, and GLOW-1, a similar trial that reported data in Apr 2011 (#msg-62261390). The main difference between these two trials is that GLOW-2 contained an open-label comparator arm where patients received PFE’s Spiriva. According to this PR, NVA237 had “similar” efficacy to Spiriva, but the PR does not say NVA237 was statsig non-inferior; we’ll have to wait until the data are presented at a medical conference to find out, but my guess is that NVA237 missed the threshold for statisg non-inferiority to Spiriva, which could be detrimental from a marketing standpoint. In any case, NVS will submit regulatory applications for NVA237 monotherapy before the end of 2011, and this product would seem to be very likely to be approved.

On the other hand, NVS’ plans to combine NVA237 and QAB149 into a product called QVA149 (to compete with such 2-drug products as GSK’s Advair) have hit a bump in the road with respect to the QAB149 (LABA) component of the combination. Following an FDA CRL in 2009 and a resubmission with more data, an FDA advisory panel in Mar 2011 rejected the 150mcg dose of QAB149 monotherapy that is used in the QVA149 combination (#msg-60733567). QAB149 monotherapy (a/k/a Onbrez Breezhaler) was approved in Europe in 2009 (#msg-41904142), so perhaps the FDA and the FDA advisory panel are being overly cautious. The PDUFA date for QAB149 monotherapy is 7/31/11.]

http://www.novartis.com/newsroom/media-releases/en/2011/1527049.shtml

›June 30, 2011 07:15 CET

Novartis Phase III study shows once-daily NVA237 is superior to placebo and similar to tiotropium in improving lung function in COPD

• GLOW2 study shows NVA237 provides superior 24-hour bronchodilation to placebo (p<0.001) with comparable efficacy to open-label tiotropium at 12 weeks

• NVA237 shown to be well-tolerated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD)

• Phase III data support first regulatory submission for NVA237 by end of 2011

Basel, June 30, 2011 - Results from the pivotal Phase III GLOW2 clinical trial show that once-daily NVA237 (glycopyrronium bromide) 50 mcg significantly improved lung function in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) relative to placebo (p<0.001), with similar efficacy to open-label tiotropium [Spiriva].

Further efficacy and safety results from GLOW2 will be presented at a scientific congress in 2012, and the data will be used to support an application for regulatory approval to be filed before the end of 2011.

"NVA237 has demonstrated its potential benefit for COPD patients in two large pivotal Phase III studies," said Trevor Mundel, MD, Global Head of Development at Novartis Pharmaceuticals. "This new study adds to the growing evidence that NVA237 could be an important treatment option for COPD, and supports our plans to develop a fixed-dose combination with our long-acting beta2-agonist Onbrez® Breezhaler® (indacaterol)" [a/k/a QVA149, a combination of NVA237 and QAB149].

In an exploratory arm of the study, NVA237 was compared with open-label tiotropium (Spiriva® HandiHaler®*) 18 mcg, another once-daily long-acting muscarinic antagonist (LAMA) indicated for the treatment of COPD. Results show that NVA237 produced similar improvements in lung function to tiotropium. [Were they statsig non-inferior?]

The study met its primary endpoint by demonstrating superior 24-hour bronchodilation to placebo at 12 weeks measured by trough FEV1 (i.e. forced expiratory volume in one second), a standard measure of lung function. NVA237 was delivered using the Concept1® device, a single-dose dry-powder inhaler.

Key secondary endpoints were improvement in breathlessness assessed using the Transition Dyspnea Index (TDI) at 26 weeks, and improved quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) at 52 weeks. Important secondary endpoints were time to first COPD exacerbation and use of rescue medication during 52 weeks of treatment. The study met all of these endpoints.

The GLOW2 study also showed that NVA237 was well-tolerated with a similar incidence of adverse events for patients treated with NVA237, placebo and open-label tiotropium.

GLOW2 was a 52-week double-blind, placebo-controlled, parallel-group study involving 1,066 patients to assess the efficacy, safety and tolerability of NVA237 in patients with COPD. Patients were randomized into three treatment arms receiving either once-daily NVA237 50 mcg or placebo (double-blind), or once-daily tiotropium 18 mcg[1] (open label). They were also permitted to use COPD background therapy and rescue medication.

In April 2011 Novartis announced results from the first Phase III clinical trial with NVA237 [#msg-62261390]. The pivotal double-blind 26-week GLOW1 study met its primary endpoint by demonstrating superior bronchodilation to placebo at 12 weeks measured by trough FEV1 (p<0.001). The incidence of adverse events was similar in NVA237-treated patients and in those receiving placebo. Further data from GLOW1 will be presented at the European Respiratory Society congress in Amsterdam in September 2011.

COPD is a progressive, life-threatening disease associated with tobacco smoking, air pollution or occupational exposure, which causes obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. COPD affects 210 million people worldwide and is projected to be the third leading cause of death by 2020. Although often considered a disease of the elderly, research has shown that a majority of COPD patients are under the age of 65 when they are likely to be at the peak of their earning power and family responsibilities.

NVA237 was licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei.‹