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European Medicines Agency Validates Bristol Myers Squibb’s Application for Zeposia (ozanimod) for the Treatment of Ulcerative Colitis

Marketing Authorization Application is supported by positive results from the pivotal Phase 3 True North study evaluating oral Zeposia (ozanimod) in adults with moderately to severely active ulcerative colitis

If approved, Zeposia would be the first oral sphingosine-1-phosphate (S1P) receptor modulator for the treatment of ulcerative colitis

PRINCETON, NJ, USA I December 28, 2020 I Bristol Myers Squibb (NYSE:BMY) today announced that the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for Zeposia (ozanimod) for the treatment of adults with moderately to severely active ulcerative colitis (UC). Validation of the application confirms the submission is complete and begins the EMA’s centralized review process.

The MAA submitted to the EMA is based on results from True North, a pivotal, placebo-controlled Phase 3 trial evaluating Zeposia as an induction and maintenance therapy in adults with moderately to severely active UC. True North met both primary endpoints, demonstrating highly statistically significant and clinically meaningful results for clinical remission compared to placebo at induction at Week 10 and in maintenance at Week 52. The overall safety observed in True North was consistent with the known safety profile for Zeposia in approved labeling.

“Ulcerative colitis is an unpredictable and potentially debilitating disease, and many patients cycle through different therapies as they try to manage their disease,” said Mary Beth Harler, M.D., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “This validation is an important step toward making Zeposia available to eligible patients in the European Union, who are in need of new treatment options offering proven efficacy and safety, as well as oral administration.”

About True North

True North is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of Zeposia 1mg in patients with moderately to severely active ulcerative colitis who did not adequately respond to prior treatment. In the induction phase, a total of 645 patients were randomized to receive Zeposia (n=429) or placebo (n=216), of whom 94% and 89%, respectively, completed the induction period. At study entry, mean age was 42 years, 60% were male and mean disease duration was 7 years; patient characteristics were well-balanced across treatment groups. Cohort 1 patients were randomized 2:1 to Zeposia or placebo and treated once daily for 10 weeks. Cohort 2 (n=367) was an open-label arm, and included to allow adequate patient numbers for the maintenance phase of the trial. Cohort 2 patients were treated once daily with Zeposia for 10 weeks.

For the maintenance phase, 457 patients were re-randomized to maintenance treatment with either Zeposia (n=230) or placebo (n=227). Of these, 80% and 54.6% of patients who received Zeposia and placebo, respectively, completed the study; disease relapse (13.5% Zeposia, 33.9% placebo) was the most common reason for discontinuation. Patients on Zeposia from either Cohort 1 or 2 who achieved clinical response in the induction phase at Week 10 were re-randomized 1:1 to Zeposia or placebo through Week 52. Patients on placebo who achieved clinical response in the induction phase at Week 10 remained on placebo during this blinded maintenance phase.

In Cohort 1 of the induction phase and in the re-randomized patient group in the maintenance phase, 30% of patients had prior TNF-inhibitor exposure.

All eligible patients were rolled into an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis.

The primary endpoints in True North are the proportion of patients in clinical remission based on a composite clinical and endoscopic score (3-component Mayo Score) at Week 10 in the induction phase, and at Week 52 for the maintenance phase. Secondary endpoints include the proportion of patients achieving clinical response at Week 10 and Week 52, the proportion of patients with endoscopic improvement (endoscopy score ≤1) at Week 10 and Week 52, the proportion of patients with mucosal healing at Week 10 and Week 52, and clinical remission at Week 52 in patients that were in remission at Week 10. In this study, mucosal healing is defined as endoscopic improvement with histologic remission. More information can be found on www.clinicaltrials.gov, NCT02435992.

About Ulcerative Colitis

Ulcerative colitis, a chronic inflammatory bowel disease (IBD), is characterized by an abnormal, prolonged immune response that creates long-lasting inflammation and ulcers (sores) in the mucosa (lining) of the large intestine (colon) or rectum. Symptoms, including bloody stools, severe diarrhea and frequent abdominal pain, usually develop over time rather than suddenly. Ulcerative colitis has a major impact on patients’ health-related quality of life, including physical functioning, social and emotional well-being and ability to work. Many patients have an inadequate response or do not respond at all to currently available therapies. It is estimated that approximately 12.6 million people worldwide have IBD.

About Zeposia (ozanimod)

Zeposia (ozanimod) is an oral, sphingosine-1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia reduces the capacity of lymphocytes to exit from lymph nodes, reducing the number of circulating lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the inflamed intestinal mucosa.

Bristol Myers Squibb is continuing to evaluate Zeposia in an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis. The company is also investigating Zeposia for the treatment of moderately to severely active Crohn’s disease in the ongoing Phase 3 YELLOWSTONE clinical trial program.

Zeposia was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with relapsing forms of multiple sclerosis (RMS) in March 2020. The European Commission approved Zeposia for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease as defined by clinical or imaging features in May 2020. Zeposia is not approved for the treatment of ulcerative colitis in any country.

U.S. FDA-APPROVED INDICATION FOR ZEPOSIA

ZEPOSIA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

For additional safety information, please see the full Prescribing Information and Medication Guide.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedInTwitterYouTubeFacebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

Marketing Authorization Application is supported by positive results from the pivotal Phase 3 True North study evaluating oral Zeposia (ozanimod) in adults with moderately to severely active ulcerative colitis

If approved, Zeposia would be the first oral sphingosine-1-phosphate (S1P) receptor modulator for the treatment of ulcerative colitis

PRINCETON, NJ, USA I December 28, 2020 IBristol Myers Squibb (NYSE:BMY) today announced that the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for Zeposia (ozanimod) for the treatment of adults with moderately to severely active ulcerative colitis (UC). Validation of the application confirms the submission is complete and begins the EMA’s centralized review process.

The MAA submitted to the EMA is based on results from True North, a pivotal, placebo-controlled Phase 3 trial evaluating Zeposia as an induction and maintenance therapy in adults with moderately to severely active UC. True North met both primary endpoints, demonstrating highly statistically significant and clinically meaningful results for clinical remission compared to placebo at induction at Week 10 and in maintenance at Week 52. The overall safety observed in True North was consistent with the known safety profile for Zeposia in approved labeling.

“Ulcerative colitis is an unpredictable and potentially debilitating disease, and many patients cycle through different therapies as they try to manage their disease,” said Mary Beth Harler, M.D., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “This validation is an important step toward making Zeposia available to eligible patients in the European Union, who are in need of new treatment options offering proven efficacy and safety, as well as oral administration.”

About True North

True North is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of Zeposia 1mg in patients with moderately to severely active ulcerative colitis who did not adequately respond to prior treatment. In the induction phase, a total of 645 patients were randomized to receive Zeposia (n=429) or placebo (n=216), of whom 94% and 89%, respectively, completed the induction period. At study entry, mean age was 42 years, 60% were male and mean disease duration was 7 years; patient characteristics were well-balanced across treatment groups. Cohort 1 patients were randomized 2:1 to Zeposia or placebo and treated once daily for 10 weeks. Cohort 2 (n=367) was an open-label arm, and included to allow adequate patient numbers for the maintenance phase of the trial. Cohort 2 patients were treated once daily with Zeposia for 10 weeks.

For the maintenance phase, 457 patients were re-randomized to maintenance treatment with either Zeposia (n=230) or placebo (n=227). Of these, 80% and 54.6% of patients who received Zeposia and placebo, respectively, completed the study; disease relapse (13.5% Zeposia, 33.9% placebo) was the most common reason for discontinuation. Patients on Zeposia from either Cohort 1 or 2 who achieved clinical response in the induction phase at Week 10 were re-randomized 1:1 to Zeposia or placebo through Week 52. Patients on placebo who achieved clinical response in the induction phase at Week 10 remained on placebo during this blinded maintenance phase.

In Cohort 1 of the induction phase and in the re-randomized patient group in the maintenance phase, 30% of patients had prior TNF-inhibitor exposure.

All eligible patients were rolled into an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis.

The primary endpoints in True North are the proportion of patients in clinical remission based on a composite clinical and endoscopic score (3-component Mayo Score) at Week 10 in the induction phase, and at Week 52 for the maintenance phase. Secondary endpoints include the proportion of patients achieving clinical response at Week 10 and Week 52, the proportion of patients with endoscopic improvement (endoscopy score ≤1) at Week 10 and Week 52, the proportion of patients with mucosal healing at Week 10 and Week 52, and clinical remission at Week 52 in patients that were in remission at Week 10. In this study, mucosal healing is defined as endoscopic improvement with histologic remission. More information can be found on www.clinicaltrials.gov, NCT02435992.

About Ulcerative Colitis

Ulcerative colitis, a chronic inflammatory bowel disease (IBD), is characterized by an abnormal, prolonged immune response that creates long-lasting inflammation and ulcers (sores) in the mucosa (lining) of the large intestine (colon) or rectum. Symptoms, including bloody stools, severe diarrhea and frequent abdominal pain, usually develop over time rather than suddenly. Ulcerative colitis has a major impact on patients’ health-related quality of life, including physical functioning, social and emotional well-being and ability to work. Many patients have an inadequate response or do not respond at all to currently available therapies. It is estimated that approximately 12.6 million people worldwide have IBD.

About Zeposia (ozanimod)

Zeposia (ozanimod) is an oral, sphingosine-1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia reduces the capacity of lymphocytes to exit from lymph nodes, reducing the number of circulating lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the inflamed intestinal mucosa.

Bristol Myers Squibb is continuing to evaluate Zeposia in an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis. The company is also investigating Zeposia for the treatment of moderately to severely active Crohn’s disease in the ongoing Phase 3 YELLOWSTONE clinical trial program.

Zeposia was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with relapsing forms of multiple sclerosis (RMS) in March 2020. The European Commission approved Zeposia for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease as defined by clinical or imaging features in May 2020. Zeposia is not approved for the treatment of ulcerative colitis in any country.

U.S. FDA-APPROVED INDICATION FOR ZEPOSIA

ZEPOSIA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

For additional safety information, please see the full Prescribing Information and Medication Guide.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedInTwitterYouTubeFacebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

Source Business Wire Health: Pharmaceutical News

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