Amprya is a new drug that is said to improve mobility for those suffering from multiple sclerosis. Many years of research have gone into the development of this amazing drug, which finally made its way into the market in March 2010 after it's FDA approval on January 22, 2010.
THE BACKGROUND
1969-1990:
Early research out of London (1969-1983) included published papers related to conduction, demyelination, ion channels, 4-AP and multiple sclerosis. The first clinical study of 4-AP and visual function in MS was published in 1983. See J Neurol Sci. 1983 Aug-Sep;60(3):353-62. Early research from Yale and Brown Universities (1977-1994) include several studies of demyelination and aminopyridine in multiple sclerosis and spinal cord injuries.
Research in Chicago (1974-1991) focused on the use of 4-AP in treatment of MS symptoms. Three small clinical trials performed at Rush Multiple Sclerosis Medical Center in Chicago were published between 1987-1991 in which researchers observed clinical benefits while also comparing oral vs. intravenous delivery of the compound. See Ann Neurol. 1987 Jan;21(1):71-7. See Ann Neurol. 1990 Feb;27(2):186-92. See Neurology. 1991 Sep;41(9):1344-8.
1990-1997:
In 1990, Elan Corporation obtained the Know-How related to fampridine (4-aminopyridine) for symptomatic treatment of multiple sclerosis from Rush-Presbyterian Hospital in Chicago. Research continued in Amsterdam (1990-1996) where several clinical studies were conducted including the first large trials of 4-AP in MS looking at its broad effects on disability (EDSS) and long-term safety and efficacy (during one trial two patients had seizures and one developed hepatitis). See Ann Neurol. 1992 Aug;32(2):123-30. See Clin Neuropharmacol. 1993 Jun;16(3):195-204. See Arch Neurol. 1994 Mar;51(3):292-6.
In 1994 and 1996, Elan obtained the patents to the sustained-released technology for Fampridine-SR (slow-release fampridine/4-aminopyridine) which had been developed by Joseph Masterson and Michael Myers. Elan also sponsored clinical research at the University of Maryland, Baltimore (1990-97) as well as the very first clinical trials of Fampridine-SR in multiple sclerosis. SeeNeurology. 1997 Apr;48(4):817-21.
1995-2004:
In March 1995, Dr. Ron Cohen founded Acorda Therapeutics, Inc. to develop therapeutic products for spinal cord injury and other central nervous system disorders. Immediately, Acorda obtained the rights to develop fampridine for therapeutic use in spinal cord injury from the Canadian Spinal Research Organization (CSRO). In January 1997, Acorda entered into another licensing agreement, this one with Elan, to develop fampridine-SR for treatment of spinal cord injury.
In April 1998, Acorda and Elan entered a joint venture and formed the MS Research & Development Corp (MSRD). MSRD turned around and licensed research and development technology from Elan to develop Elan's proprietary oral sustained release formulation of fampridine for the treatment of multiple sclerosis. MSRD was permanently terminated in September 2003 when Acorda entered into agreements with Rush and Elan, terminating the Rush license to Elan with mutual releases. In the process Rush granted Acorda worldwide license to the Know-How and Orphan Drug Designation to fampridine for treatment in MS.
In December 2000, Accorda had announced they would initiate a Phase II trial of Fampridine-SR in MS (MS-F201). Results of that dose-ranging study were presented at the Sept 2002 ECTRIMS meeting but weren't fully published until 2007. See Mult Scler. 2007 Apr;13(3):357-68. Epub 2007 Jan 29. In April 2004, Acorda announced that Phase III clinical studies of Fampridine-SR in spinal cord injury did not produce the desired statistically-significant results, but that positive data from a second Phase II trial in MS (MS-F202) confirmed results from previous Phase II trials.
2005-2008:
Acorda Therapeutics turned to developing Fampridine-SR for use in MS announcing in May 2005 that they had worked out a Special Protocol Assessment (SPA) with the FDA for their phase III trial design. On April 7, 2006, Acorda’s President and CEO Ron Cohen rang the opening bell on Wall Street to celebrate their successful IPO launch. In September 2006, Acorda announced positive Phase III results (MS-F203) which were later presented at the AAN meeting in May 2007 and the ACTRIMS meeting in Washington, DC in June 2007. Results from this 1st Phase III trial were finally published in The Lancet in February 2009. See Lancet 2009; 373: 732–38.
In January 2008, Acorda announced positive data from a successful QT safety study which is required by the FDA for all new drugs seeking regulatory approval. In June 2008, Acorda announced positive results from the 2nd Phase III study of Fampridine-SR in MS (MS-F204). Results from this second Phase III trial have yet to be published.
2008-2010:
In March 2008, Acorda announced the results from a commissioned survey focused on Mobility and Quality of Life. Also in the spring of 2008, Acorda sponsored several MS Walks throughout the country. Walk MS is one of the larger fundraisers for the NMSS. In conjunction, Acorda launched the non-branded outreach website titled “I Walk Because” which features videos and profiles of MS patients and Walk MS participants.
In January 2009, Acorda submitted their New Drug Application (NDA) to the FDA for approval of Fampridine-SR (which is now called AMPYRA). The FDA Central Nervous System Advisory Committee held a meeting on October 14, 2009 to evaluate the clinical significance of AMPYRA (referred to as Amaya or Ampriva at the time) for improving walking ability in MS patients. Detail regarding the various clinical trials and data leading up to this approval can be found in the 177-page document (pdf) prepared for the FDA Committee meeting.
Data from the Phase III trials suggest that only some patients may derive a clear benefit and selectivity in responsiveness might be related to the proposed mechanism of action where only some patients would be expected to have axons (nerves) susceptible to the drug effects at any given time.
The FDA Committee voted 12 to 1 that clinical data on Fampridine-SR 10 mg twice daily demonstrated substantial evidence of effectiveness as a treatment to improve walking in people with multiple sclerosis (MS) and voted 10 to 2 (1 abstention) that it is clinically meaningful and can be safe for use. But due to the increased risk of seizures associated with the drug and concerns about the use of Fampridine-SR in patients with renal impairment, the Committee also recommended by a vote of 12 to 1 that Acorda be required to evaluate the effects of doses lower than 10 mg twice daily, but by a 10 to 2 vote (1 abstention) that these studies not be required prior to approval. Lower doses are not expected to be available for at least two or three years, if at all.
On January 22, 2010, FDA announced that they had awarded marketing approval for AMPYRA™ (dalfampridine, 10mg extended release tablet taken twice daily) as a treatment to improve walking in MS patients. AMPYRA™ will be marketed in the United States by Acorda Therapeutics and out of the US by Biogen Idec who purchased those rights last June 2009.
