Three of the 20 drugs currently being developed for primary progressive multiple sclerosis (PPMS) are now in Phase III of development, according to leading data and analytics company GlobalData, offering hope to the patients, who have very few treatment options in comparison to patients affected by relapsing remitting multiple sclerosis (RRMS).

MS is an autoimmune disease that causes chronic inflammation and damages the myelin sheath that protects nerves.

According to research by GlobalData’s pharma team, the three drugs in Phase III development are tolebrutinib (anticipated launch in 2025 in the US and 2026 in the 5EU*), AB Science’s masitinib (anticipated launch in 2027 in the US and in the 5EU) and Roche’s fenebrutinib (anticipated launch in 2027 in the US and 2028 in the 5EU).

Barbora Salcman, Neurology Analyst at GlobalData, comments: “Tolebrutinib and fenebrutinib are particularly exciting, as they offer a new targeted mechanism of action (MoA) for MS: these drugs inhibit Bruton’s tyrosine kinase (BTK) to selectively target B-cell activity. Masitinib also acts via a novel MoA for MS, but is less targeted, instead inhibiting multiple tyrosine kinases. Both of these strategies offer very different approaches from existing oral disease-modifying therapies. Any agents with novel MoAs and improved efficacy will be a welcome addition for patients diagnosed with progressive MS—particularly PPMS.

PPMS patients represent around 10–15% of the total patient population. Only Roche’s Ocrevus (ocrelizumab) is currently available for these patients and its efficacy is limited.

Salcman continues: “Based on data from a pivotal Phase III (NCT01194570) clinical trial, Ocrevus improved disability progression after 24 weeks by around 25%, which is quite low, considering that, for example, Novartis’s Mayzent (siponimod) showed efficacy of around 37% in slowing disease progression in patients with secondary progressive MS after 24 weeks. Ocrevus is also not approved for use in countries such as Japan, leaving patients in this country without any effective treatment options.”

While all three Phase III agents have the benefit of being new MoAs, masitinib has already showcased impressive results at Phase II/III.

Salcman continues: “Masitinib has shown positive results in its Phase II/III clinical trial in PPMS (NCT01433497), with a low dose of the agent decreasing disability progression by 42% over the course of 96 weeks—over 1.5 times the results seen in a separate study for Ocrevus. Regarding safety, in contrast to Ocrevus, masitinib showed no risk of infection, and in general caused only mild and moderate side effects, such as diarrhea, rash, or swelling. The situation is less clear for tolebrutinib and fenebrutinib, as both agents are currently awaiting Phase III trial results in PPMS following highly successful Phase II trials in RMS. As progressive MS has a different pathogenesis in comparison to RMS, it remains to be seen how effective BTK inhibitors will be for treating PPMS.”

Alongside these three drugs in Phase III development, the rest of the pipeline includes four Phase I and 12 Phase II drugs.