New Drug Approval Case Study: USFDA approval of Zeposia, delayed market launch likely due to COVID-19

U.S. Food and Drug Administration (FDA) has approved ZEPOSIA^® (ozanimod) 0.92 mg for the treatment of adults with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

• Brand Name: Zeposia
• Active Ingredient: Ozanimod
• USFDA approved use: To treat relapsing forms of multiple sclerosis

With the FDA approval of ZEPOSIA, appropriate patients with relapsing forms of multiple sclerosis will have another oral treatment option with meaningful efficacy to help address the disease’s hallmark relapses and brain lesions.

BMS said it decided to delay rolling out the drug during the pandemic COVID-19.

Clinical Basis of Approval:

The approval is based on data from the largest pivotal, head-to-head RMS studies with an active comparator to date: the randomized, active-controlled Phase 3 SUNBEAM™ (safety and efficacy of ZEPOSIA versus interferon beta-1a in relapsing multiple sclerosis) and RADIANCE™ (safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ZEPOSIA in relapsing multiple sclerosis) Part B clinical trials of more than 2,600 adults. In both trials – as compared to AVONEX^® (interferon beta-1a), ZEPOSIA delivered powerful efficacy as measured by annualized relapse rate (ARR), as well as on the number and size of brain lesions.

• ZEPOSIA demonstrated a relative reduction in ARR versus AVONEX of 48% through one year and 38% at two years (absolute ARR of 0.18 versus 0.35 and 0.17 versus 0.28, respectively).
• At one year, treatment with ZEPOSIA reduced the number of T1-weighted gadolinium-enhanced (GdE) brain lesions more than AVONEX (0.16 vs 0.43), a relative reduction of 63%, and reduced the number of new or enlarging T2 lesions (1.47 vs. 2.84), a relative reduction of 48%.
• At two years, treatment with ZEPOSIA reduced the number of T1-weighted gadolinium-enhanced (GdE) brain lesions more than AVONEX (0.18 vs 0.37), a relative reduction of 53%.^1,2 ZEPOSIA also reduced the number of new or enlarging T2 lesions vs AVONEX (1.84 vs 3.18), a relative reduction of 42%.

There was no statistically significant difference in the three-month and six-month confirmed disability progression between ZEPOSIA- and AVONEX- treated patients over two years. ZEPOSIA demonstrated acceptable safety and tolerability in the Phase 3 SUNBEAM and RADIANCE Part B trials.

A Marketing Authorization Application for ZEPOSIA for the treatment of adults with relapsing-remitting multiple sclerosis in the European Union is currently under review with the European Medicines Agency (EMA). A regulatory decision from the EMA is expected in the first half of 2020.

About SUNBEAM™

SUNBEAM is a pivotal, phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of oral ZEPOSIA (0.92 mg, equivalent to 1 mg) against weekly intramuscular AVONEX^® (interferon beta-1a) for at least a 12-month treatment period. The study included 1,346 people living with RMS across 152 sites in 20 countries.

The primary endpoint of the trial was annualized relapse rates (ARR) during the treatment period. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 12 months and number of gadolinium-enhanced brain MRI lesions at month 12.

An analysis of the time to onset of three-month confirmed disability progression was pre-specified using pooled data from both the SUNBEAM and RADIANCE Part B phase 3 trials.

About RADIANCE™

RADIANCE Part B is a pivotal, phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of oral ZEPOSIA (0.92 mg, equivalent to 1 mg) against weekly intramuscular AVONEX^® (interferon beta-1a) over a 24-month treatment period. The study included 1,320 people living with RMS across 150 sites in 21 countries.

The primary endpoint of the trial was ARR over 24 months.² The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 24 months.

An analysis of the time to onset of three-month confirmed disability progression was pre-specified using pooled data from both the SUNBEAM and RADIANCE Part B phase 3 trials.