Bristol Myers Squibb’s Zeposia (ozanimod) Receives Positive CHMP Opinion as First Oral S1P Receptor Modulator for Ulcerative Colitis in the EU
Oct 18, 2021 00:49
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00:49
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Committee for Medicinal Products for Human Use
Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.
Ulcerative colitis (UC, image source: healthjade.com)
October 16, 2021 /BioonBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of a new indication for Zeposia (ozanimod): for the treatment of patients who have had an inadequate response to, lost response to, or are intolerant of conventional therapy or biologics.Adult patients with moderate to severe active ulcerative colitis (UC)。The active pharmaceutical ingredient of Zeposia, ozanimod, is an oral sphingosine-1-phosphate (S1P) receptor modulator that selectively binds to S1P receptor subtypes 1 (S1P1) and 5 (S1P5) with high affinity.
The CHMP opinion will now be submitted to the European Commission (EC) for review, which is expected to make a final decision in the fourth quarter. If approved,Zeposia will become the first and only oral sphingosine-1-phosphate (S1P) receptor modulator approved in the European Union for the treatment of ulcerative colitis (UC).. In the United States, Zeposia was approved in May 2021, becoming the first oral S1P receptor modulator for the treatment of UC in the United States. The drug is indicated for the treatment of adult patients with moderately to severely active UC. Notably, for this indication, Bristol-Myers Squibb to the United StatesFDAA Priority Review Voucher (PRV) was submitted to expedite the review.
Positive CHMP Opinion and the USFDAThe approval was based on the results of the pivotal Phase 3 TRUE NORTH study (NCT02435992). This was a placebo-controlled study evaluating the efficacy and safety of Zeposia as an induction and maintenance therapy for adult patients with moderately to severely active ulcerative colitis (UC). The results showed that,Compared with the placebo group, the Zeposia treatment group demonstrated significant improvements in all primary and secondary efficacy endpoints at Weeks 10 and 52 (including clinical remission, clinical response, endoscopic improvement, and endoscopic histologic mucosal improvement).The overall safety observed in this study was consistent with the known safety profile in the approved labeling for Zeposia.
Bristol-Myers SquibbImmunologyand Jonathan Sadeh, M.D., Senior Vice President of Fibrosis Development, stated: “Despite the availability of existing treatments, many patients with UC still struggle to effectively manage this often unpredictable disease, making the availability of diverse treatment options critically important. Zeposia has the potential to be a truly transformative therapy and is the first and only oral S1P receptor modulator for the treatment of ulcerative colitis. With this positive opinion from the CHMP, we are one step closer to bringing Zeposia to patients in the European Union.”
The TRUE NORTH study (NCT02435992) was a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy and safety of Zeposia as induction and maintenance therapy in adult patients with moderate-to-severe UC. Results demonstrated that the study met its two primary endpoints: at Week 10 of induction and Week 52 of maintenance, Zeposia showed highly statistically and clinically significant improvements in both primary and key secondary endpoints compared with placebo.
——At Week 10 of the induction period (Zeposia group n=429 vs placebo group n=216), the trial met the primary endpoint of clinical remission (18% vs 6%, p<0.0001) as well as key secondary endpoints, including clinical response (48% vs 26%, p<0.0001), endoscopic improvement (27% vs 12%), and endoscopic-histologic mucosal improvement (13% vs 4%, p<0.001).
——At Week 52 of the maintenance phase (Zeposia group n=230, placebo group n=227), the trial met the primary endpoint of clinical remission (37% vs 19%, p<0.0001) and key secondary endpoints, including clinical response (60% vs 41%, p<0.0001), endoscopic improvement (46% vs 26%, p<0.001), corticosteroid-free clinical remission (32% vs 17%), and endoscopic-histologic mucosal improvement (30% vs 14%, p<0.001). In patients treated with Zeposia, reductions in rectal bleeding and stool frequency subscores were observed as early as Week 2 (i.e., 1 week after completion of the required 7-day dose titration).
Based on the study results, Zeposia is the first oral S1P receptor modulator to demonstrate clinical benefit in the treatment of moderate to severe UC in a Phase 3 study. The overall safety profile observed in the study was consistent with the known safety profile in Zeposia's approved label.
Molecular structure of ozanimod (Image source: Wikipedia)
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by an abnormal, persistent immune response that causes chronic inflammation and ulceration in the mucosa (lining) of the large intestine (colon). Symptoms include bloody stools, severe diarrhea, and frequent abdominal pain, which typically develop gradually over time rather than abruptly. UC significantly impacts patients' health-related quality of life, including physical functioning, social and emotional well-being, and work capacity. Many patients exhibit an inadequate response or no response at all to currently available therapies. It is estimated that 12.6 million people worldwide are affected by IBD.
The active pharmaceutical ingredient of Zeposia, ozanimod, is an oral sphingosine-1-phosphate (S1P) receptor modulator that selectively binds to S1P receptor subtypes 1 (S1P1) and 5 (S1P5) with high affinity.
In March 2020, Zeposia received U.S.FDAApproved for the treatment of adults with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. In May 2020, Zeposia was approved by the European Commission for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease (defined by clinical or imaging features).
Currently, Bristol-Myers Squibb is developing Zeposia for multiple immuno-inflammatory indications, including Crohn's disease (CD) in addition to multiple sclerosis (MS) and ulcerative colitis (UC). Phase III YELLOWSTONEClinical TrialThe study is evaluating Zeposia for the treatment of patients with moderately to severely active CD. The mechanism of action of Zeposia in the treatment of UC and CD is not fully understood, but it may be related to the reduction of lymphocyte migration into the inflamed intestinal mucosa. (Bioon.com)