Weak Phase III data have dealt a blow to Vectura’s (LON:VEC) hopes of seeing Flutiform approved for use in chronic obstructive pulmonary disease (COPD) patients. Vectura shares fell as much as 10% after it revealed the Phase III study missed its primary endpoint, quashing near-term hopes of expanding the use of a drug it acquired in the £441 million ($576 million) merger with Skyepharma.
Vectura’s partner Mundipharma enrolled 1,767 patients in the study and randomized them to receive one of two doses of Flutiform or an active comparator, formoterol. After 52 weeks of daily dosing with the drugs, the study team analyzed the annual rate of moderate and severe COPD exacerbations in each arm. The key comparison was between the higher dose of Flutiform and the long-acting beta2 agonist (LABA) formoterol. Mundipharma was hoping to see evidence Flutiform is better at controlling COPD exacerbations than formoterol.
In this regard, the experimental therapy fell short, resulting in the trial missing its primary endpoint. Mundipharma is now digging through the other endpoints, which compared the lower Flutiform dose to formoterol and looked at exacerbations, lung function and safety in each of the arms. But the failure to meet the primary endpoint has scuttled Mundipharma’s plan to apply for approval in Europe on the strength of the Phase III data.
That news was seen by investors as serious enough to send shares in Vectura down 10% in early trading in London, although the stock rallied to make up some of the losses by midmorning. Faced with lengthening odds of LABA-inhaled corticosteroid (ICS) combination Flutiform winning approval in COPD, Vectura CEO James Ward-Lilley sought to play up both the challenge of improving on standard of care and the potential to grow sales in other indications.
“COPD is a complex and highly variable disease and these trial results highlight the challenge in demonstrating reductions of exacerbations with ICS/LABA combinations in today’s treatment environment,” Ward-Lilley said in a statement. “Whilst this result is disappointing, flutiform continues to grow strongly based on the approved asthma indication.”
Flutiform racked up sales of €92.4 million in the first 6 months of 2016, an increase of 42% over the comparable period of 2015. But, while there is still scope for Vectura to grow sales of Flutiform in its existing asthma indication, the potential loss of the COPD market nonetheless represents a blow to the company's plans to build its business and justify the merger with Skyepharma.
The failure of the addition of an ICS to a LABA to improve on the latter alone is in keeping with data from other COPD drug developers. GlaxoSmithKline ($GSK) and Theravance Biopharma ($TBPH) encountered a similar setback during the development of Breo, but ultimately succeeded in winning approval for the once-daily ICS/LABA.