Results of post hoc analyses of pivotal phase 3 trials assessing the efficacy of the investigational compound ozanimod (Celgene, Summitt, NJ) versus interferon ß-1a (IFN) (Avonex; Biogen, Cambridge, MA) for treatment of patients with relapsing multiple sclerosis (MS) were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Berlin, Germany Oct. 10-12.
Compared to patients treated with IFN, patients treated with either 1 mg and 0.5 mg doses of ozanimod for at least 1 year had improvements of 1.6 (95% CI: 0.62-2.56) and 1.2 (95% CI: 0.19-2.13), respectively, in their score on the Symbol Digit Modalities Test (SDMT), a measure of cognitive processing speed. More patients had clinically meaningful increases of at least 4 points on the SDMT when treated with ozanimod 1 mg (rate ratio 1.3; 95% CI 1.05-1.55) or .5 mg (rate ratio 1.2; 95% CI: 0.94-1.40) than those who were treated with IFN.
In these studies, early relapsing MS was defined as having an Expanded Disability Status Scale (EDSS) of 3.5 or more, being diagnosed within the last 3 years, and having no or only 1 treatment. The annualized rates of relapse (ARR) in patients with early disease (n = 1,392) who were treated with ozanimod at doses of 1 mg (ARR = 0.149) or 0.5 mg (ARR = 0.200) were lower than for patients treated with IFN (ARR = 0.285). In patients with more advanced disease (n=1,267) (ozanimod 1 mg: 0.217; 0.5 mg: 0.277; IFN: 0.363).
Patients with early relapsing MS treated with ozanimod had a lower mean number of T1 gadolinium-enhancing (ozanimod 1 mg, .263; ozanimod 0.5 mg, .458) compared to those treated with IFN (.656). For patients with more advanced disease, the mean numbers of T1 gadolinium-enhancing lesions were also lower with ozanimod (1 mg, 0.278; 0.5 mg, 0.323; and IFN, 0.915). Mean numbers of new or enlarging T2 lesions on MRI were also lower in patients treated with ozanimod (1 mg, 2.952; 0.5mg, 3.744) versus IFN (4.633); for patients with more advanced disease, the mean number of new or enlarging T2 lesions were 2.514, 2.903 and 4.710, respectively.
Ozanimod is a novel, oral, selective sphingosine 1-phosphate 1 (S1P1) and 5 (S1P5) receptor modulator in development for immune-inflammatory indications (eg, MS, ulcerative colitis, or Crohn's disease). Selective binding with S1P1 is believed to inhibit a subset of activated lymphocytes from migrating to inflammation sites, reducing the number of circulating T and B lymphocytes leading to anti-inflammatory activity without limiting immune surveillance. Selective binding to S1P5 is also thought to activate cells of the central nervous system that could enhance remyelination and prevent synaptic defects.
The most common adverse reactions (≥ 5 percent) that were higher with ozanimod than with IFN were upper respiratory tract infections, urinary tract infections, increases of alanine aminotransferase, and increases of gamma-glutamyl transferase.Next Story