A New Dawn for Progressive MS: Immunic's Vidofludimus Calcium Shines in Phase 2 Trials

The pharmaceutical landscape for progressive multiple sclerosis (PMS) has long been barren. Unlike relapsing-remitting MS, where therapies like Ocrevus and Mavenclad have slowed disease activity, PMS—particularly primary progressive MS (PPMS)—has seen only two FDA-approved treatments in over a decade: siponimod (Mayzent) and the controversial ocrelizumab (Ocrevus). Both offer marginal benefits, with siponimod reducing disability progression by just 21% in one trial. Now, Immunic, Inc. (NASDAQ: IMUN) is poised to disrupt this landscape with vidofludimus calcium, a drug that has shown promising Phase 2 results in both relapsing and progressive MS. The key? A novel mechanism targeting neuroprotection—a critical unmet need in a disease where neurons wither over time.

The Unmet Need in Progressive MS

PMS affects roughly 15–20% of MS patients, yet it remains the most devastating form of the disease. Unlike relapsing MS, where treatments can suppress inflammation, progressive MS is marked by relentless neurodegeneration. Current therapies only address inflammatory pathways, leaving the core issue—neuronal death—untreated. The market for PMS therapies is projected to grow to $2.5 billion by 2030, but the pipeline is thin. Immunic's vidofludimus could fill this gap.

The Science Behind Vidofludimus Calcium

Vidofludimus's dual-action profile sets it apart. It inhibits DHODH, a enzyme critical for RNA and DNA synthesis in immune cells, thereby reducing inflammation. But its true innovation lies in activating Nurr1, a nuclear receptor that boosts the production of neuroprotective proteins like brain-derived neurotrophic factor (BDNF) and superoxide dismutase 1 (SOD1). This mechanism directly addresses neurodegeneration, a first in the MS space. Preclinical data showed it protected neurons under stress and reduced microglial activation—a hallmark of MS pathology.

Phase 2 Results: A Strong Foundation

In the Phase 2 CALLIPER trial, vidofludimus reduced disability progression by 20% in the overall PMS population, with a striking 30% reduction in PPMS patients—the hardest-to-treat subgroup. The drug also slowed thalamic brain volume loss by 20%, a key biomarker of neurodegeneration. Notably, even patients without active inflammation (as measured by no gadolinium-enhancing lesions) saw a 34% reduction in disability worsening, underscoring its neuroprotective role.

In relapsing MS trials, the drug's safety and efficacy were equally compelling. The EMPhASIS open-label extension showed 92% of patients remained free of confirmed disability worsening over 144 weeks, with minimal adverse events. Over 950 patient-years of data revealed no new safety signals—a critical advantage over older MS drugs like tysabri, which carry risks of PML.

Safety: The Critical Edge for Long-Term Use

Long-term safety is the linchpin for any MS therapy, given the chronic nature of the disease. Vidofludimus's 5.5-year safety data, with low discontinuation rates and no cumulative toxicity, is a game-changer. This contrasts sharply with therapies like Tecfidera, which carries a black box warning for progressive multifocal leukoencephalopathy. For investors, this profile reduces regulatory and commercial risks, as insurers and neurologists are more likely to favor drugs with proven long-term tolerability.

Market Potential and Regulatory Path

With Phase 3 trials in relapsing MS (ENSURE) expected to report by late 2026, and discussions with regulators about PPMS trials already underway, Immunic is on track for potential approvals by 2028. If successful, vidofludimus could carve out a $1 billion+ annual revenue stream in PMS alone. Its oral formulation—a rarity in advanced MS therapies—adds to its commercial appeal.

Risks and Considerations

Investors must weigh risks. Phase 3 trials could stumble; siponimod's PPMS data failed before its relapsing success. Additionally, competition looms. Roche's RG6107 (a NLRP3 inhibitor) is in Phase 2 for PPMS, while Biogen's anti-LINGO-1 antibody is in early trials. Still, vidofludimus's unique neuroprotective mechanism gives it a distinct advantage.

The Investment Thesis

Immunic's stock (IMUN) trades at a market cap of ~$250 million, a fraction of its potential if vidofludimus gains even modest adoption. With a $50 million cash runway through 2025, the company is well-positioned to navigate upcoming milestones. Early investors in Biogen (during the interferon era) or Alexion (pre-Soliris) saw 10x returns on similar breakthroughs. Vidofludimus's dual-action profile and robust safety data position Immunic as a high-reward, high-risk play—ideal for investors willing to bet on transformative neurology therapies.

Conclusion

Progressive MS has been the “last frontier” of MS treatment. Immunic's vidofludimus calcium, with its neuroprotective mechanism and long-term safety, is the closest contender yet to breach this frontier. For patients and investors alike, the next 18 months—marked by Phase 3 readouts—will be pivotal. If history is any guide, therapies that address unmet needs in neurodegenerative diseases command premium valuations. The question isn't whether vidofludimus works in trials, but whether Immunic can scale its potential into a commercial powerhouse. The data so far suggests they're well on their way.