Sanofi and its subsidiary Genzyme announced that 12 data presentations, including six platform presentations, from the company’s multiple sclerosis (MS) clinical trial programmes for alemtuzumab and teriflunomide will be featured at the American Academy of Neurology's (AAN) 64th Annual Meeting in New Orleans, from April 21-28.
Presentations will include full data results from CARE-MS II (The Comparison of alemtuzumab and Rebif Efficacy in Multiple Sclerosis), a phase III trial investigating alemtuzumab in MS patients who had relapsed while receiving prior MS therapy, as well as new findings from the teriflunomide clinical programme, one of the largest and broadest of any MS therapy in development.
“Genzyme’s robust development programmes for alemtuzumab and teriflunomide were designed to understand how these therapies can best address significant unmet medical needs of people living with MS,” said David Meeker, MD, president and CEO, Genzyme. “We are committed to becoming a long-term partner to the MS community with the goal of raising the expectation of what life with MS can be.”
Marketing applications for teriflunomide for the treatment of relapsing forms of MS are under review by the US Food & Drug Administration (FDA) and European Medicines Agency (EMA). Genzyme is on track to submit applications to the FDA and EMA for approval of alemtuzumab to treat relapsing forms of MS in the second quarter of this year.
Following are selected scientific abstracts highlighting new results from the phase III CARE-MS II and CARE-MS I trials for alemtuzumab, as well as the phase III TEMSO (Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis) trial for teriflunomide.
Alemtuzumab is a monoclonal antibody that selectively targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time. Although the exact mechanism of effect in MS is unknown, this repopulation creates a re-balanced immune system that potentially reduces MS disease activity.
In addition to the completed CARE-MS II study, another phase III trial, CARE-MS I, evaluated alemtuzumab against Rebif (interferon beta-1a) in relapsing-remitting MS patients naive to prior treatment and found a statistically significant reduction in relapse rate with alemtuzumab. In both trials, alemtuzumab 12 mg was given as an IV administration on eight days over the course of the two-year study. The first treatment course of alemtuzumab was administered on five consecutive days, and the second course was administered on three consecutive days 12 months later. Rebif 44 mcg was administered by subcutaneous injection three times per week, each week, throughout the two years of study.
Genzyme has the worldwide rights to alemtuzumab and has primary responsibility for the development and commercialization in MS. Bayer HealthCare has been co-developing alemtuzumab in MS with Genzyme. Bayer HealthCare retains an option to co-promote alemtuzumab in MS and upon regulatory approval and commercialization would receive contingent payments based on sales revenue.
Teriflunomide, a once daily oral tablet, is an immunomodulator with a unique mechanism of action. Although the mechanism of action for teriflunomide is not fully understood, research supports that teriflunomide inhibits the proliferation of stimulated T and B lymphocytes in the periphery thought to be responsible for the damaging inflammatory process in MS, while generally maintaining normal immune function. Teriflunomide selectively and reversibly inhibits DHODH, a key enzyme in de novo pyrimidine synthesis required by rapidly dividing lymphocytes. Through this effect, it limits the expansion of stimulated T- and B-cells in the periphery and diminishes the numbers of activated T- and B-cells available to migrate into the central nervous system (CNS). Because the salvage pathway for pyrimidine synthesis is not affected by teriflunomide, resting lymphocytes maintain their viability and remain unaffected by teriflunomide.
Teriflunomide is being studied in a large clinical program that is expected to include more than 5,000 trial participants in 36 countries. Six efficacy clinical trials are either completed or underway with teriflunomide, making the clinical program one of the largest of any MS agent under development. In addition to the completed TEMSO and TENERE trials, the phase III, placebo-controlled trial TOWER was recently completed in people with relapsing forms of MS. Another phase III study, TOPIC, is underway in early MS or CIS (clinically isolated syndrome). Teriflunomide is also being evaluated as an adjunctive therapy to interferon-ß in the phase III TERACLES trial. With up to 10 years of continuous use in a phase II extension, teriflunomide has the longest clinical experience of any investigational oral MS therapy.
Genzyme, a Sanofi company, has pioneered the development and delivery of transformative therapies for patients affected by rare and debilitating diseases and focussed on rare diseases and multiple sclerosis, dedicated to making a positive impact on the lives of the patients and families they serve.