Phase III RADIANCE trial, evaluating the efficacy and safety of Ozanimod, an investigational oral, selective S1P 1 and 5 receptor modulator, in patients with relapsing multiple sclerosis ( RMS ), met the primary endpoint in reducing annualized relapse rate ( ARR ), compared to weekly Interferon ( IFN ) beta-1a ( Avonex ).
RADIANCE evaluated two doses ( 0.5 mg and 1 mg ) of oral Ozanimod, with patients treated for two years. The trial enrolled 1,313 RMS patients in 21 countries.
Both Ozanimod 0.5 mg and 1 mg doses demonstrated statistically significant and clinically meaningful reductions in the primary endpoint of ARR and the key secondary endpoints of the number of new or enlarging T2 MRI lesions over 24 months of treatment compared to Avonex and the number of Gadolinium-enhancing MRI lesions at 24 months of treatment compared to Avonex.
In a pre-specified pooled analysis of the time to confirmed disability progression in both the RADIANCE and SUNBEAM phase III trials, a very low rate of disability progression was observed across the three treatment groups, and ozanimod did not reach statistical significance compared to Avonex.
Additionally, both doses of Ozanimod demonstrated statistically significant reductions in brain atrophy compared to Avonex in each phase III trial.
The overall safety and tolerability profile was consistent with results from the recently completed phase III SUNBEAM RMS trial and previously reported phase II trials.
The results of the phase III RADIANCE trial have confirmed the data observed in SUNBEAM and are consistent with the long-term phase II RADIANCE trial.
The significant effects seen with Ozanimod on relapse and MRI outcomes, including brain volume loss, coupled with the safety and tolerability profile observed in the two phase III trials, represent an exciting advancement for a disease which needs additional oral therapies with favorable benefit-risk profiles.
RADIANCE is a pivotal, phase III multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of two doses of oral Ozanimod ( 0.5 mg and 1 mg ) against weekly intramuscular interferon beta-1a over a 24 month treatment period.
The primary endpoint of the trial is ARR over 24 months. The key secondary endpoints are: the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 24 months and the number of GdE brain MRI lesions at month 24.
An analysis of the time to onset of disability progression was pre-specified using pooled data from both the SUNBEAM and RADIANCE phase III trials.
SUNBEAM is a pivotal, phase III multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of two doses of oral Ozanimod ( 0.5 mg and 1 mg ) against weekly intramuscular interferon beta-1a over a 24 month treatment period. The study included 1,346 RMS patients across 152 sites in 20 countries.
The primary endpoint of the trial was ARR during the treatment period. The key secondary endpoints were: the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 12 months and the number of GdE brain MRI lesions at month 12.
Ozanimod is a novel, oral, selective, sphingosine 1-phosphate 1 ( S1PR1 ) and 5 ( S1PR5 ) receptor modulator in development for immune-inflammatory indications including relapsing multiple sclerosis, ulcerative colitis and Crohn's disease.
Selective binding with S1PR1 receptors is believed to inhibit a specific sub set of activated lymphocytes from migrating to sites of inflammation. The result is a reduction of circulating T and B lymphocytes that leads to anti-inflammatory activity. Importantly, immune surveillance is maintained.
Selective binding with S1PR5 receptors is believed to activate specific cells within the CNS. This has the potential to enhance remyelination and prevent synaptic defects. Ultimately, neurological damage may be prevented.
Multiple sclerosis is a disease in which the immune system attacks the protective myelin sheath that covers the nerves. The myelin damage disrupts communication between the brain and the rest of the body. Ultimately, the nerves themselves may deteriorate, a process that's currently irreversible.
Signs and symptoms vary widely, depending on the amount of damage and the nerves affected.
Some people with severe multiple sclerosis may lose the ability to walk independently, while others experience long periods of remission during which they develop no new symptoms.
Multiple sclerosis affects approximately 400,000 people in the U.S. and approximately 2.5 million people worldwide.
RMS is characterized by clearly defined attacks of worsening neurologic function. These attacks ( often called relapses, flare-ups or exacerbations ), are followed by partial or complete recovery periods ( remissions ), during which symptoms improve partially or completely, and there is no apparent progression of disease.
RMS is the most common disease course at the time of diagnosis. Approximately 85 percent of people are initially diagnosed with relapsing multiple sclerosis, compared with 10-15 percent with progressive forms of the disease. ( Xagena )
Source: Celgene, 2017