Multiple Sclerosis | Disease Landscape and Forecast | G7 | 2016

The maturing, but highly lucrative, market for multiple sclerosis (MS) disease-modifying therapies (DMTs) is becoming increasingly fragmented as attractive new options enter a powerful armamentarium—one transformed by oral drugs but in which injectable mainstays have given way only slowly. Beginning in 2017, we expect Novartis’s siponimod and Roche/Genentech’s ocrelizumab (Ocrevus) to become the first compelling approved agents to treat progressive MS, which will expand DMT use in these underserved populations. In relapsing MS, Novartis/Mitsubishi Tanabe Pharma’s Gilenya/Imusera, Biogen’s Tecfidera, and Sanofi Genzyme’s Aubagio are now well established in early lines of therapy, although the safety experience with these drugs prolongs a clinical role for platform injectable therapies (e.g., interferon-βs, Teva’s Copaxone). In later lines of treatment, Genzyme/Sanofi’s Lemtrada and Biogen/AbbVie’s Zinbryta vie for use with Biogen’s Tysabri; standout Ocrevus will drive further competition late-line but will also stoke the perennial debate about induction. The first generic MS DMT, Sandoz/Momenta’s Glatopa (glatiramer acetate 20 mg/mL), has done little to date to change the U.S. market access landscape in MS, but additional generics, namely orals, loom; we expect that generic competition will limit the market potential for a growing wave of follow-on products in the late-stage MS pipeline. Meanwhile, drug developers have resharpened their focus on developing “next frontier” neuroprotective or reparative treatments, although major challenges remain. Ultimately, the launch of premium-priced novel therapies, coupled with U.S. price increases and growth in the drug-treatment rate for progressive MS, will combine to drive relatively steady growth in the market through 2025; however, this growth will be tempered by a conservative prescriber base faced with a relative lack of long-term safety data and clinical experience with novel agents, as well as a lack of prognostic and theranostic markers needed to help guide tough treatment decisions.

Questions Answered:

• At long last, approved treatment options for secondary- (SP-MS) and primary-progressive multiple sclerosis (PP-MS) are in sight. In which patient types do interviewed MS experts expect to use siponimod and Ocrevus for progressive MS? How large is the commercial opportunity for these agents in the progressive MS population, and what competitors might they face down the road?
• Generic glatiramer acetate 20 mg/mL has entered the U.S. market, and we expect that the next five years will see the launch of additional generic competitors, including oral DMTs. What will be the commercial impact of these lower-priced alternatives on the MS market, and when will it occur?
• Oral DMTs led by Gilenya/Imusera and Tecfidera hold a sizable share of the relapsing MS market, with follow-on agents rapidly progressing through the pipeline. How will oral DMTs fare against attractive new monoclonal antibodies in the evolving MS treatment algorithm? How will ozanimod (Celgene/Receptos), ponesimod (Actelion), ALKS-8700 (Alkermes), and FP-187 (Forward Pharma) compete with their first-generation counterparts? How large a role can Teva/Active Biotech’s laquinimod and Merck KGaA’s oral cladribine achieve in the increasingly crowded landscape? 
• Potent—and acceptably safe—immune-targeted DMTs are necessary for treatment-refractory MS patients and those with an aggressive disease course. Thanks to risk stratification for progressive multifocal leukoencephalopathy (PML), Biogen’s Tysabri remains competitive and Lemtrada Zinbryta and Ocrevus offer additional late-line options. How will neurologists’ use of Tysabri change? What is the market outlook for other higher-risk/higher-reward DMTs (e.g., Lemtrada)? Are physicians receptive to Zinbryta? How will experts utilize Ocrevus and ofatumumab (Novartis/Genmab)in the management of relapsing MS patients? How might these agents impact treatment paradigms? 
• Injectable DMTs remain a bedrock of current treatment. How will the role of IFN-β products and glatiramer acetate evolve? What clinical and commercial forces will shape the longevity of the platform injectable products?

Scope:

Markets covered: United States, France, Germany, Italy, Spain, United Kingdom, Japan.

Primary research: 31 country-specific interviews with experts.

Epidemiology: Prevalence of relapsing-remitting MS and clinically isolated syndrome (RR-MS + CIS); prevalence of chronic-progressive MS (CP-MS).

Population segments in market forecast: RR-MS + CIS; CP-MS.

Emerging therapies: Phase II: 17 drugs; Phase III: 7 drugs; preregistration: 2 drugs. Coverage of 11 select preclinical and Phase I products.