Follow-up data from TOPIC, CARE-MS II trials positive for the two MS drugs.
At the 69th Annual Meeting of the American Academy of Neurology this week in Boston, Massachusetts, Sanofi Genzyme announced additional investigational data on two different multiple sclerosis drugs stemming from follow-ups in phase 3 trials.
Teriflunomide (Aubagio), has been FDA-approved since 2012 and is an oral treatment for relapsing multiple sclerosis. Data announced at the meeting came from the TOPIC trial, designed to assess whether early initiation of the drug following a first clinical episode of MS might delay or prevent progression to clinically definite multiple sclerosis (CDMS). In the trial, patients on both 7mg and 14mg regimens were “significantly less likely than placebo (p<0.05) to develop CDMS, the primary endpoint.”
The crux of the terflunomide announcement, however, had to do with cortical gray matter atrophy. The drug was shown to have a “consistent and significant effect on reducing cortical gray matter atrophy across all time points evaluated over two years,” according to a news release from the company. Cortical gray matter volume (CGMV) was measured using SIENAX multi-time point analysis at baseline and every 6 months for two years, roughly 200 patients were in the placebo, 7mg, and 14mg groups.
The comparative retention vs. placebo was higher throughout, but varying: 58.2% in the 7mg group (P=0.071) and 119.2% in the 14mg group at 6 months (P=0.017); 79.8% (P=0.054) and 61.4% (p=0.036) respectively at 12 months; 69.5% (p=0.004) and 66.8% (p=0.003) at 18 months; evening out to 46.0% and 40.2% (p=0.042) at 24 months.
“In accordance with the reduced risk of conversion to CDMS and indicates that teriflunomide may favorably impact the early neurodegenerative component of MS,” that study concluded.
The company’s other announcement regarded alemtuzumab (Lemtrada), and included 6 years of extension data from the CARE-MS II study. The twice-annually infused drug was studied in patients with relapsing-remitting multiple sclerosis (RRMS) judged to have highly active disease (HAD), defined as “≥2 relapses in the year prior to randomization and ≥1 gadolinium-enhancing lesion at baseline.” The extension period followed the 2 year core study, focused on disease progression, and allowed patients to receive as-needed alemtuzumab or other disease-modifying treatment.
Patients either received the alemtuzumab infusions twice per year or 44μg of interferon-beta 1a (SC IFNB-1a) 3 times per week. The study assessed patients on multiple metrics, including
Functional Assessment of MS (FAMS); a short-form 36-item survey (SF-36) that had both physical (PCS) and mental (MCS) component summaris; and EuroQol-5 dimensions visual analog scale (EQ-5D).
In each case, the drug seemed to provide what the study called “durable efficacy in the absence of continuous treatment.”
Perhaps most significantly to the company, the results indicated that a disease relapse did not necessarily spell a lack of response to the drug. “The 24% of Lemtrada-treated patients in CARE-MS II who relapsed between their first and second courses experienced a marked improvement in clinical and MRI disease activity at year 2, which was maintained through sixe years,” the official press release quotes Barry Singer, MD, the Director of the MS Center for Innovations in Care at Missouri Baptist Medical Center in St. Louis.
In patients who had relapsed between treatment courses, annual relapse rate declined continuously from year 1 through year 6, and in those who had not relapsed, the rate maintained a low of 0.2 until dropping to 0.1 in year 6. In those who had relapsed, 80% were also free of confirmed disease worsening between years 1 and 2, dipping to 60% by year 6, with even higher number in the non-relapsing group.
Both studies were presented in poster sessions at the conference and naturally featured research sponsored by Sanofi Genzyme.