Spiriva Finds COPD Exacerbation Studies Can Be An Exasperating Experience

As competitors tout comparative data, Boehringer hopes a Nov. 19 advisory committee on its claim for reduction in exacerbations will lead to a broader label.

Boehringer Ingelheim is seeking to expand its indication for Spiriva HandiHaler (tiotropium inhalation powder) to include its use against exacerbation of chronic obstructive pulmonary disease, something GlaxoSmithKline's market-leading Advair (fluticasone/salmeterol inhalation powder) did in 2008 that put it in a league of its own.

Boehringer's drug faces an advisory panel hurdle - FDA's Pulmonary-Allergy Drugs Advisory Committee is set to discuss the supplemental NDA on Nov. 19 - but the firm is hoping to benefit from the lessons of GSK's hard-won approval.

The agency issued a "not approvable" letter for Advair's initial application for a survival and reduced exacerbations claim in 2007, asking for head-to-head data against a reduced strength (Also see "FDA Grants GSK's Advair Broader Use" - Pink Sheet, 30 Apr, 2008.).

New data on exacerbation reduction

At the European Respiratory Society Annual Congress September 15, 2009, BI revealed data from a new post-hoc analysis from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial, which showed that based on 356 patients under the age of 50, those treated with Spiriva had a 27 percent decreased risk of exacerbations compared with patients in the control group.

In a press release announcing the new findings, BI noted that "exacerbations can worsen the clinical course of the disease, therefore a treatment such as tiotropium that significantly reduces the number of COPD exacerbations may provide patients with an improved disease prognosis and impact the clinical course of COPD."

The same analysis also demonstrated that Spiriva administered to younger patients with COPD resulted in statistically significant reductions in the rate of lung function decline and improvements in health-related quality of life. The younger patient population showed a 34 percent reduction in the rate of lung function decline over four years when treated with Spiriva compared to age-matched controls.

Spiriva's current indication was based on six Phase III studies in 2,663 patients 40 years old and older with COPD.

Furthermore, a pre-specified subgroup analysis of UPLIFT recently published in The Lancet showed that Spiriva reduced the rate of decline in post-bronchodilator FEV1 over 4 years compared with control. The rate of decline in pre-bronchodilator FEV1 was similar between the groups, and Spiriva also resulted in an 18 percent lower risk for exacerbations and 20 percent fewer exacerbations compared with control.

Staying ahead of the pack

Spiriva is currently indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema. BI's label expansion efforts come as a growing number of companies seek a presence in the COPD field.

Novartis is building a respiratory franchise based around QAB149 (indacaterol), pending in the U.S. and the EU for once-daily treatment of COPD: The company has exclusive global rights to QMF149, a drug in Phase II development for asthma and COPD that combines QAB149 and Schering Plough's Asmanex (mometasone). Novartis also has a licensing partnership with U.K.-based Vectura Group for NVA237 in development for monotherapy and in combination with QVA149 for treatment of COPD.

Novartis claims data released at the American Thoracic Society conference May 18, 2009, show that once-daily QAB149 delivered clinically relevant lung function results, with improvement seen over Spiriva at three months of treatment (Also see "Taking A Deep Breath: Novartis & Schering Split Respiratory Product Rights, Giving Novartis Indacaterol" - Pink Sheet, 25 May, 2009.).

AstraZeneca, which has a COPD indication for the Symbicort pressured metered dose inhaler approved in February, is on track to launch in China, Australia and Canada in the second half of 2009 (Also see "AstraZeneca’s Symbicort On Advair’s Heels With COPD Approval" - Pink Sheet, 9 Mar, 2009.). Symbicort SMART, a dry powder inhaler device, is only available outside the U.S. [Editor's note: this story was updated Sept. 29 to clarify where Symbicort SMART is marketed.]

Vivitrol has a COPD therapy in the works - ALKS-27 is currently in Phase II development.

Forest Laboratories recently inked a deal with Nycomed as its commercialization partner for Daxas (roflumilast), a promising oral COPD drug, which recently turned up positive Phase II data. The August 28 issue of Lancet reports that Daxas consistently improved lung function and reduced exacerbations in patients with moderate to severe chronic obstructive pulmonary disease.

The commercialization partnership paid Nycomed $100 million upfront, plus undisclosed regulatory and commercial milestones (Also see "Forest Acquires U.S. Rights To Nycomed's Oral COPD Drug Daxas" - Pink Sheet, 10 Aug, 2009.). That deal (now vindicated by the positive trial results) managed to fill a sudden void in Forest's pipeline, which nixed an oral PDE-4 candidate in COPD with partner Glenmark on Aug. 18 after it failed to prove efficacious in a Phase IIb dose-ranging study (Also see "Good Showing For Nycomed's COPD Drug Daxas" - Pink Sheet, 27 Aug, 2009.).

-Lauren Smith ([email protected])