CDER, Shire enter agreement for ProAmatine clinical trial to treat symptomatic orthostatic hypotension

Dec 3 2011

Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, announces that it has reached an agreement with the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA) to conduct additional clinical trials to confirm the clinical benefit of ProAmatine® (midodrine HCl), a medicine approved in 1996 under Subpart H (an accelerated approval process) for the treatment of symptomatic orthostatic hypotension (SOH). 

This joint clinical trials proposal from CDER and Shire is being reviewed by the FDA Commissioner and, if accepted, will negate the need for a public hearing requested by Shire on this topic.  Under the agreement, Shire will conduct two additional clinical trials and expects to begin the trials as soon as possible with an anticipated completion by the end of 2014.  Midodrine HCl in its generic formulations will remain available to patients who rely on this medicine while the trials are conducted. 

"The timeframe outlined in the proposal for additional clinical trials is consistent with Shire's original request and we are appreciative that we have come to agreement with CDER on this path forward," said Jeffrey Jonas, M.D., Senior Vice President of Research & Development for Shire.  "We've been committed to completing these additional clinical trials to confirm the efficacy of midodrine as a treatment for SOH and keep this important medication available for patients."

Shire is the New Drug Application (NDA) holder for midodrine HCl, which had been marketed by Shire until 2010 under the brand name ProAmatine.  Shire has no financial interest in midodrine, and no longer manufactures, distributes or markets the brand name version of midodrine HCI, ProAmatine.  Beginning in 2003, midodrine has been manufactured and distributed by generic pharmaceutical companies.  As the NDA holder, Shire has continued to invest in the needed regulatory processes and has worked diligently with FDA to develop a path forward that would allow the NDA to maintain its marketing authorization thus allowing the generic versions of ProAmatine to remain available for patients who critically need this medicine and who have no alternative treatments to manage their SOH symptoms. 

ProAmatine was approved in 1996 under Subpart H (an accelerated approval process) for the treatment of SOH, with a post-approval commitment to conduct two clinical trials to confirm the clinical benefit of midodrine.  The initial approval was based on ProAmatine's demonstrated ability to significantly raise blood pressure in patients with SOH.  In 2000, Shire acquired ProAmatine and completed two clinical post-marketing trials as required and submitted the results to FDA in 2005.  FDA took the position that these trials were inadequate and requested that additional trials be completed.  Shire disagrees with the FDA and believes that these trials, together with 15 years of clinical experience, have established the clinical efficacy of ProAmatine and provide the necessary data to support the full approval of ProAmatine.

"This Shire agreement with CDER to conduct additional clinical studies that further demonstrate the clinical efficacy of midodrine as a treatment for SOH is in the best interest of patients and we are very pleased for those patients and their families that we have reached this outcome and are hopeful this proposal will be approved," added Jonas. 

SOURCE Shire plc