SkyePharma's Asthma Drug Finally Approved in Europe
By Nuala Moran
LONDON The asthma treatment Flutiform finally won the seal of the European Commission last week, more than 12 years after SkyePharma plc set its sights on what it thought would be the relatively straightforward development of a combination product based on two marketed drugs.
Instead, the project left a trail of corporate wreckage in its wake, including the ousting of the company's founder, failed marketing deals, downsizing, a mountain of debt and rejection by the FDA.
Finally looking forward to the first of 21 launches in national markets in Europe before the end of 2012 CEO Peter Grant admitted, "It has taken a very long time."
Despite the reduction in patent exclusivity that this implies, "The competitive position has not changed," Grant told BioWorld Today. SkyePharma has achieved its oft-rehearsed ambition of being the third to have a combination asthma product on the market after GlaxoSmithKline plc's Advair and AstraZeneca plc's Symbicort.
"Flutiform has genuine benefits and offers the best combination of a steroid and LABA [long-acting beta 2-agonist]," said Grant.
Flutiform combines the corticosteroid fluticasone propionate with the LABA formoterol fumarate, formulated with SkyePharma's SkyeDry technology, which keeps the individual components separate and stable, and ensures a consistent, reproducible dose of each is delivered from a single aerosol inhaler. The SkyeDry formulation has patent protection until 2019.
The label allows Flutiform to be used for the regular treatment of asthma in people 12 and older whose symptoms are not adequately controlled on a corticosteroid and an as-required short-acting beta 2 agonist.
Under the agreement with marketing partner Mundipharma International Corp. Ltd., London-based SkyePharma will receive up to €15 million (US$18.4 million) in milestones as Flutiform is launched in major European markets, with a further €40 million to follow in sales-related milestones.
Royalties will start at 10 percent of net sales, with the possibility of increasing to a maximum of 35 percent of net sales. However, initially Mundipharma will retain some of the royalties as compensation for its investment in getting Flutiform through to approval.
Mundipharma previously paid SkyePharma €15 million up front when the deal was signed in September 2006, and a further €3 million milestone in December 2008.
According to the market analysts IMS Research, the total European market for asthma drugs was $8.6 billion in 2010, with combination products taking $4.8 billion of that. SkyePharma is responsible for supplying Flutiform, which will be manufactured by Sanofi SA at its facility in Holmes Chapel, UK. Some initial launch stocks have been manufactured already.
Grant was not able to comment on the pricing of Flutiform, which he said will be up to Mundipharma and its negotiations with national pricing and reimbursement bodies.
Sanofi also is marketing partner for Flutiform in South America, and European approval will feed into submissions in markets including Mexico, Brazil and Argentina.
"The EU approval is a key plank it will be largely the same dossier, and Sanofi is working on submissions," Grant said. In addition, SkyePharma's Japanese partner Kyorin Pharmaceutical Inc., announced last month that is has successfully completed Phase III development and is in line to file for approval in March 2013. Grant is searching for a Canadian marketing partner also.
The Long, Winding Road
It was in April 2000 that the founder, Ian Gowrie-Smith, announced the company was raising a £60 million (US$93 million) loan to fund a change in strategy, in which rather than solely providing drug delivery services, SkyePharma would start to develop its own products.
Work started on Flutiform in 2002, with formal clinical development getting under way in 2004. Gowrie-Smith found himself under fire in October 2005 when he raised $61 million in a heavily discounted rights issue to fund the U.S. Phase III development of Flutiform after ditching a $160 million marketing deal because he claimed the [unnamed] partner was moving too slowly.
Gowrie-Smith and CEO Michael Ashton were subsequently forced out just before Phase III U.S. development endorsed by the FDA began in February 2006.
Kos Pharmaceuticals, now part of Abbott, was signed as U.S. partner in a $165 million agreement in May 2006, but despite that deal, in January 2007, SkyePharma was forced to take out a high interest loan to see the program home.
There was a further setback in August 2007, when issues raised by the FDA in a pre-NDA meeting added $6 million to $10 million to the development costs and delayed filing until March 2009. A worse blow came in January 2010, when concerns about the safety of LABAs as a whole, led the FDA to refuse to approve Flutiform.
SkyePharma subsequently reacquired U.S. rights to Flutiform from Abbott in August 2010. Grant did not sound optimistic on the question of whether European approval will push open the door with the FDA, saying SkyePharma would only go forward in the U.S. if it found a partner to fund the further clinical development and post-approval safety study that is required for U.S. approval.
SkyePharma receives royalties on 12 marketed products that use its drug delivery technologies, but Grant said it is "very exciting" to finally be able to talk about a product where the company did a substantial part of the development. That includes carrying out eight Phase I/II studies and nine Phase III trials, in which 1 ,900 people received Flutiform.
"This endorses our credibility as one of the very few independent providers of drug delivery technologies with the ability to develop complex products," he said.
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