Bristol Myers Squibb's Multiple Sclerosis Drug Zeposia Rejected by NICE Over Cost-Effectiveness Concerns

Compiled by Fan Dongdong

Despite Bristol-Myers Squibb (BMS) providing substantial evidence demonstrating the clear benefits of the multiple sclerosis drug Zeposia (ozanimod) for patients, regulatory bodies, including the UK’s National Institute for Health and Care Excellence (NICE), have recently continued to question the drug’s pricing.

NICE Provisionally Rejects Oral S1P Modulator Zeposia in Consultation Document. Although the pricing negotiations between Bristol-Myers Squibb (BMS) and the UK government are confidential, the consultation document indicates that NICE does not consider the estimated cost-effectiveness of this drug to fall within the range of resource use acceptable to the National Health Service (NHS), when compared with other first-line treatments for relapsing-remitting multiple sclerosis (RRMS).

NICE listed several obstacles encountered by its reviewers in determining the cost-effectiveness of Zeposia. For instance, the agency stated that Bristol-Myers Squibb (BMS) initially offered access to this drug for all patients with relapsing-remitting multiple sclerosis, but later restricted the patient population submitted for review to those with active disease who preferred oral therapy. This additional restriction confused NICE analysts, as the new criteria made it difficult to identify which patients within the eligible population genuinely preferred oral medication over injectable treatments.

In its document, NICE stated, “The committee is concerned that limiting the patient population would avoid comparing the drug with other treatments within NHS resources.” The agency proposed several methods to improve the cost analysis of Zeposia, one of which involves comparing the drug with second-line therapies such as Sanofi’s Lemtrada and Roche’s Ocrevus. BMS appeared intent on avoiding such a comparison, responding that patients with multiple sclerosis currently need convenient treatment options more than ever before. In a statement, the company said, “BMS believes that providing oral therapy to patients is particularly important during the ongoing COVID-19 pandemic, as it can reduce the need for hospital visits for clinical treatment.” Notably, Zeposia is indeed the first and only S1P receptor modulator that does not require first-dose observation.

Zeposia is an oral medication taken once daily. In March last year, the drug received approval from the U.S. Food and Drug Administration (FDA). In May last year, Bristol-Myers Squibb announced that the European Commission (EC) had approved the drug for the treatment of adult patients with active relapsing-remitting multiple sclerosis (RRMS), as defined by clinical or imaging features. Originally developed by Celgene, the approval of Zeposia marks the first new drug application (NDA) approved by the U.S. FDA since Bristol-Myers Squibb’s acquisition of Celgene, expanding Bristol-Myers Squibb’s portfolio in immunology.

The approvals in the United States and the European Union were both based on data from SUNBEAM and RADIANCE, the largest head-to-head pivotal Phase 3 clinical trials conducted to date in patients with multiple sclerosis. These two multinational trials enrolled more than 2,600 patients across 150 sites in over 20 countries worldwide. Results from the SUNBEAM trial showed that Zeposia reduced the annualized relapse rate by 48% over one year. Compared with Avonex, Zeposia also achieved a relative reduction of 63% in the number of T1-weighted gadolinium-enhancing (GdE) brain lesions and a relative reduction of 48% in the number of new or enlarging T2 lesions. In the RADIANCE study, Zeposia reduced the annualized relapse rate by 38% over two years of treatment. Compared with Avonex, Zeposia resulted in a relative reduction of 53% in the number of T1-weighted GdE brain lesions and a relative reduction of 42% in the number of new or enlarging T2 lesions.

The prices of multiple sclerosis drugs have remained consistently high. Although Zeposia’s annual wholesale acquisition cost (WAC) in the United States is as high as $86,000 per year, this price tag is lower than that of Novartis’s competing product, Mayzent, which is priced at $88,500 annually. However, this price advantage does not appear to be reflected in sales performance; by the end of the third quarter of 2020, Zeposia’s sales amounted to only $3 million. Nevertheless, David Elkins, Chief Financial Officer of Bristol-Myers Squibb (BMS), expressed satisfaction with physicians’ feedback on the Zeposia treatment regimen during the company’s earnings conference call. BMS confidently projects that Zeposia will ultimately generate approximately $5 billion in annual revenue.

Currently, NICE is widely soliciting external feedback on its appraisal of Zeposia and may ultimately revise its recommendation. In a statement, Bristol-Myers Squibb (BMS) expressed disappointment with the draft guidance, noting that “BMS recognizes the unmet clinical need among patients with relapsing multiple sclerosis in the UK.” The company plans to submit additional clinical evidence to NICE to help demonstrate the therapeutic benefits of Zeposia for adult patients with relapsing-remitting multiple sclerosis.

References:

1.Bristol Myers Squibb’s MS newcomer Zeposia gets the thumbs-down from England's price police

2.NICE no for BMS’ multiple sclerosis drug Zeposia

3.NICE rejects multiple sclerosis drug Zeposia