No More Needles? Laurie Long 11/14/07 |
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There are currently six drugs available to slow the progression of MS (Avonex, Betaseron, Copaxone, Rebif, Novantrone and Tysabri). But whether you get it once a day or once a week, subcutaneous or intramuscular, you’re facing the needle over and over again. Effective oral drugs for MS have been a sought-after solution for a long time. Now, multiple drug companies are racing each other and the clock to get US Food and Drug Administration (FDA) approval for their particular offerings.
Most of the drugs below are currently in Phase III trials (the last trial phase before applying for FDA approval), which generally last 2-3 years. Time is also required to collate the data, apply to the FDA for new drug approval, and receive that approval. If it can meet the requirements, a drug can receive Priority Review, which speeds up the process of FDA review.
The big questions now are: what are these drugs, how do they work, how effective are they, what are their potential side effects and when will they gain FDA approval and hit the market? Let’s take a look…
Laquinimod – sponsored by Teva Neuroscience and Active Biotech AB, Laquinimod initiated enrollment in Phase III trials on 11/7/07. The Phase III trials will last 2 years. Laquinimod is an orally administered, once daily 0.6 mg dose. In Phase II trials, MRI disease activity was reduced by 40% in relapsing remitting MS (RRMS) patients. It was well tolerated in those patients with only some transient increases in liver enzymes. If you are interested in participating in the Phase III trial, see Clinical Trial Information on www.ClinicalTrials.gov.
Fingolimod (FTY720) - sponsored by Novartis Pharma and Bayer, is a daily, orally-administered disease modifying treatment for RRMS. Fingolimod keeps the immune system's T cells in the lymph nodes and away from the central nervous system. Fingolimod reduced annual relapse rates by more than 50% compared to placebo and reduced MRI (magnetic resonance imaging) inflammation, with approximately 80% of patients free of active brain lesions. The most common adverse events reported were nasopharyngitis, headache, and influenza. The Phase III trial started in June 2006 and will run for two years. It is still recruiting. Local recruitment centers are MS Center at Evergreen (425-899-5370), Seattle Neuroscience Institute at Swedish Medical Center (206-215-3565) and Virginia Mason Multiple Sclerosis Center (206-625-7373 Ext. 61386). For more info see Clinical Trial Information.
Mylinax (Oral Cladribine) – sponsored by Merk Serono & IVAX. Mylinax is a daily, orally-administered disease modifying treatment for RRMS. Mylinax interferes with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are involved in the pathological process of MS. Previous clinical trials showed positive effects of cladribine administered via injection in patients with multiple sclerosis. In these trials, reduction in new lesion development in the brain as seen on MRI scans and clinical benefits were observed. Oral cladribine was designated a Fast Track product by the FDA in September 2006. Under Fast Track designation, oral cladribine is eligible for Priority Review and the FDA may consider portions of the marketing application for review before the new drug application is completed. Phase III trials completed enrollment in January of 2007 and will last 2 years.
Teriflunomide – sponsored by Sanofi-Aventis, Teriflunomide is a daily, orally-administered disease modifying treatment for RRMS and SPMS. It is thought to prevent the interaction of T cells in the immune system involved in damage to the myelin sheath. Those on placebo during the original trial who switched to teriflunomide experienced up to an 85% decrease in new, active areas of disease activity seen on MRI and a lower relapse rate; while the high-dose group had fewer patients experience an increase in disability. Treatment was well tolerated; though headaches and nausea were both reported. Currently recruiting for their Phase III trial (see Clinical Trial Information) which will last two years.
BG-12 – sponsored by Biogen Idec, BG-12 is an oral fumarate for relapsing-remitting MS. It is an immunomodulator with a combination of cytoprotective and anti-inflammatory properties. A Phase II controlled clinical trial of oral BG-12 led to a 69% reduction in active inflammation on MRI scans in 257 people with RRMS. In the 24-week trial, the oral drug had a significant impact on enhancing, T2, and T1 lesions seen on MRI and resulted in a 32% reduction in relapses, but the latter effect was not statistically significant. The drug was well tolerated. The most common adverse events were flushing, gastrointestinal disorders, headache, and nasopharyngitis. Phase III clinical trials began in January of 2007, but are still recruiting (see Clinical Trial Information). Trials will last two years.
CDP323 – sponsored by UBC and Biogen Idec, CDP323 is an oral VLA-4 antagonist (as is Tysabri). The safety & tolerability of CDP323 have been evaluated in healthy volunteers in three separate Phase I studies. CDP323 was well tolerated with an adverse event profile comparable to the placebo. A Phase II study began in June of 2007 and the results are expected by the end of 2008.
So when will these drugs be approved? If all goes well with the trials, Novartis hopes to submit FTY720 (Fingolimod) for FDA approval in 2009, although with Mylinax (oral Cladribine) in the FDA’s fast track, they may be neck and neck in the home stretch, with their competitors not far behind.
Bibliography
Initiation of Enrollment in Pivotal Phase III Clinical Study of Oral Laquinimod for Relapsing-Remitting Multiple Sclerosis. Teva Pharmaceutical Industries Ltd.(11/7/07)
Teva and Active Biotech to Initiate Pivotal Phase III Trial Program of Oral Laquinimod for Relapsing Multiple Sclerosis. Teva and Active Biotech (06/08/07)
Laquinimod cuts multiple sclerosis relapse. Pharmabiz.com (05/05/07)
New Preclinical Data Suggests FTY720 May Repair or Reduce Damage Caused by Multiple Sclerosis Through a Direct Effect in the Brain. Novartis (10/15/07)
Preclinical Studies Suggest FTY720 Mechanisms In Multiple Sclerosis May Include Direct Activity In The Brain. Novartis (05/05/07)
The Roskamp Institute is Participating in a New Phase III MS Study to Evaluate the Efficacy and Safety of FTY720, a Novel, Investigational, Once-Daily Oral Medication. The Roskamp Institute (5/1/07)
Novartis Pharmaceuticals initiates new world-wide Phase III study for Fingolimod (FTY720). Novartis Pharmaceuticals (10/13/06)
Biogen Idec Initiates Phase III Clinical Program of Oral Compound BG-12 for Multiple Sclerosis. Biogen Idec (1/9/07)
Biogen Idec to Acquire Fumapharm AG; Consolidates Ownership of Oral Compound BG-12 Being Studied for Multiple Sclerosis. Biogen Idec (5/31/06)
Oral Compound BG-12 Achieves Primary Endpoint in Phase II Study of Relapsing-Remitting Multiple Sclerosis; Treatment with BG-12 Led to Statistically Significant Reductions in MRI measures. Biogen Idec (5/30/06)
Merck Serono Has Initiated the ONWARD Study to Evaluate Oral Cladribine as Add-on Treatment for Multiple Sclerosis. Serono International S A (1/24/07)
Merck Serono Completes Patient Enrollment in CLARITY Phase III Pivotal Clinical Trial of Oral Cladribine. Serono International S A. (1/16/07)
Serono's Oral Cladribine for the Treatment of Multiple Sclerosis Awarded Fast Track Status by FDA. Serono International S A (9/21/06)
Phase III Trial of Oral Cladribine, a Novel Investigational Therapy for Multiple Sclerosis, Begins in the United States. Serono Press Release (05/04/06)
Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis. http://clinicaltrials.gov/show/NCT00134563 (11/11/07)
Teriflunomide in Phase III. http://www.mstrust.org.uk/research/drugsindevelopment/teriflunomide.jsp (5/23/07)
A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. http://www.neurology.org/cgi/content/abstract/66/6/894 NEUROLOGY 2006;66:894-900
Positive Results Reported For Oral Teriflunomide For Relapsing MS. National Multiple Sclerosis Society Research Bulletin (5/12/06)
UCB Announces Positive Results in Neurology and Inflammation Products UCB. Press contacts UCB - Investor Relations contacts (12/03/04)
Small Molecule Compound Being Studied For The Treatment Of Relapsing-Remitting Multiple Sclerosis. http://www.ucb-group.com (10/5/06)
UCB and Biogen Idec to Collaborate on Oral Multiple Sclerosis Therapy. UCB (10/2/06)
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