Merck's Rebif Maintains EMA Approval Despite 26% Revenue Drop and Shrinking Market Position
EMA Approval Status and Regulatory History
The European Medicines Agency (EMA) has confirmed that Merck Europe B.V.'s Rebif (interferon beta-1a) retains its valid marketing authorization in the European Union. This recombinant protein binds to interferon alpha/beta receptors (IFNAR1/IFNAR2) to modulate inflammatory immune responses in multiple sclerosis (MS), functioning as a disease-modifying therapy (DMT). The initial EU approval was granted on May 4, 1998, with the most recent renewal on May 4, 2008, and the product remains on the market. The U.S. Food and Drug Administration (FDA) also approved Rebif for the treatment of relapsing MS on March 7, 2002.
Approval Scope and Clinical Position
The EU indication includes patients at high clinical risk for MS due to a single demyelinating event with active inflammation, as well as those with relapsing MS. However, it is not indicated for secondary progressive MS without relapses, as efficacy has not been demonstrated in this population, thereby delineating its prescribing scope. Rebif is a subcutaneous injection in the approved and marketed phase, with its core assets being accumulated long-term safety data and regulatory stability. The EMA's continued approval reflects ongoing post-marketing safety monitoring and product information management, rather than new efficacy evidence.
Competition from High-Efficacy and Oral Therapies
The current MS treatment market features over 20 DMTs, with prescribing trends shifting from interferon-based injectables like Rebif toward high-efficacy monoclonal antibodies and oral therapies. Key competitors include Roche's Ocrevus (ocrelizumab, CD20), Novartis' Kesimpta (ofatumumab, CD20), Biogen's Tecfidera (dimethyl fumarate, Nrf2 pathway), and Avonex (interferon beta-1a). As clinical strategies increasingly favor early high-efficacy treatment, Rebif's convenience and efficacy in a weekly dosing regimen face competitive pressure. However, its long-standing use and predictable safety profile continue to serve as prescribing rationale for certain patient groups.
Market Performance and Business Implications
The global MS treatment market was valued at $21.07 billion in 2025, but Rebif's net sales for the same year were €465 million, a 26% decline from €626 million in 2024. This reflects a shift in treatment paradigms and declining market share for a mature product, rather than an overall market contraction. Merck KGaA's oral therapy Mavenclad (cladribine) recorded €1.194 billion in 2025, signaling a portfolio shift within the company. Thus, while the EMA's approval continuation is positive for cash flow sustainability, it is unlikely to serve as a catalyst for reversing Rebif's structural revenue decline.
Rebif remains an approved and marketed long-term asset, but its 2025 revenue of €465 million reflects a 26% year-over-year decline, indicating a divergence between EMA approval and commercial growth. In the 2025 MS treatment market valued at $21.07 billion, CD20-targeting high-efficacy therapies such as Roche's Ocrevus and Novartis' Kesimpta, along with Biogen's Tecfidera and generic oral therapies, are driving prescribing shifts. For Merck KGaA, managing Rebif's residual cash flow while transitioning its portfolio toward Mavenclad, which generated €1.194 billion in revenue, is critical. From a research and business development perspective, long-term safety alone is insufficient for competitiveness; next-generation DMTs that demonstrate dosing convenience, relapse suppression, and delay in disability progression will determine mid-to-long-term value assessment.
Source: EMA (ema)