A day after US regulators issued Chelsea Therapeutics with a complete response letter on Northera as a treatment for symptomatic orthostatic hypotension, despite earlier support for the drug, Shire has reaffirmed its commitment to complete trials to verify the benefit of midodrine, a treatment it no longer markets.
Shares in Chelsea have taken a bashing after the US Food and Drug Administration asked for more data regarding its filing for Northera (droxidopa) for SOH. This came as something of a surprise given that the agency's Cardiovascular and Renal Drugs Advisory Committee voted 7-4 in favour of the therapy last month.
Following the news, Shire gave an update on trials it will be conducting on the hypotension drug ProAmatine (midodrine) to preserve the latter's marketing approval. Currently there are no alternative FDA-approved treatments for SOH.
In August 2010, the US Food and Drug Administration said it wanted to withdraw ProAmatine (midodrine) which was approved in the USA in 1996 under the accelerated approvals process. However, according to the agency, neither Shire nor any generic firm (the drug went off-patent in 2003) has since demonstrated ProAmatine's clinical benefit.
Shire came to an agreement with the FDA to conduct two additional trials to confirm the clinical benefit of midodrine, a deal which is "especially important" in light of the CRL for droxidopa, said Shire R&D chief Jeffrey Jonas.
The Ireland-based company marketed ProAmatine until 2010 but now has no financial interest and does not manufacture or distribute the drug. Generics firms started selling the treatment in 2003, but Shire is still the holder of the New Drug Application for midodrine.
Dr Jonas added that "even though Shire no longer generates revenue from midodrine, we've agreed to invest more time and resources in additional clinical trials because we know it's the right thing to do for patients". He added that preliminary work on the two trials is underway "and we anticipate completion in the first half of 2014."
As for Chelsea, it believes that results from an ongoing study of Northera "could potentially meet the criteria for clinical efficacy and durability of effect data identified in the CRL". Chelsea adds that "notably, the letter did not identify any outstanding concerns".