A variety of new treatments for multiple sclerosis (MS) have been introduced over the past 20 years, and there are some promising developments in the pipeline. “It is time for the next step,” according to Dr. Daniel Vitt, the CEO and President of Immunic Therapeutics.
As there is no cure, treatments for MS, a chronic and often debilitating neurological condition, include therapies aimed to reduce the risk of relapses and assault to the central nervous system. The majority of these therapies have been in use since the early 1990s and are effective in managing only certain phases of the disease, such as relapsing-remitting MS (RRMS).
Approximately 10% of patients are diagnosed with primary progressive MS, and there is only one FDA-approved therapy intended for this phase. RRMS can progress to secondary-progressive and current treatment options have little effect in slowing down the disease process.
There are a few promising treatments in development, and one of them is Immunic’s approach, says Dr. Vitt. With their Phase 3 RRMS Trial nearing completion, Immunic is highlighting the safety profile of their small molecule investigational drug, vidofludimus calcium, otherwise known as IMU-838. By blocking the activity of an immune cell enzyme known as dihydroorotate dehydrogenase (DHODH), vidofludimus calcium has known anti-inflammatory effects. According to Immunic, IMU-838 selectively targets hyperactive immune cells, allowing the immune system to continue to fight infection.
At the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum in late February, Immunic presented data showing a clear separation of vidofludimus calcium from placebo in serum neurofilament light (NFL) chain levels across all progressive MS patients and beyond. The results provided biomarker evidence that the activity of IMU-838 extends beyond its anti-inflammatory effects in offering neuroprotective activity, shown in their Phase 2 CALLIPER Interim Analysis. Vidofludimus calcium, therefore, will offer something new for MS patients.
The PMS interim data is important as it has shown that both important subgroups, primary progressive MS (PPMS) and secondary progressive MS (SPMS), are likely benefiting from vidofludimus calcium. According to Dr. Vitt, there is a linear transformation of lab data and thinking to the clinical biomarker. Both subgroups had a similar 20% reduction of NFL chain biomarker in the interim analysis. The conclusion is a prediction of an even larger benefit on preventing disability worsening in the two-year readout due in 2025.
In consideration of management for relapsing MS, Dr. Vitt believes the future of treatment is in combination therapy. Current treatment has solved over 50% of the problem, says Vitt, addressing relapses but with some side effects. Anti-CD20 antibodies do a good job of decreasing the number of relapses and relapse-associated worsening (RAW), but what part of treatment in this subset of patients is unmet?
The future of MS therapy
The future of MS treatment goes beyond managing relapse and targets neuroprotection. Vidofludimus calcium’s ability to activate the neuroprotective transcription factor Nurr1 is what gives it its direct neuroprotective properties. A subsequent focus of Immunic has been on targeting progression, independent of relapse activity. As Dr. Vitt explains, “This is what we should talk about, because this is what patients have in mind when they think about their disease.”
As MS patients on anti-CD20 treatment begin to feel well, they remain acutely aware of the potential for relapse. Dr. Vitt explains “we need to give them a tool that allows them to recover from the permanent alert that occurs in their brain.” Given the early diagnosis and longevity of a lot of these patients, they need a treatment that can be tolerated yet does not increase their risk of cancer or toxicities, which can complicate their lives over time.
Combination therapy makes the most sense given Immunic’s drug is different from what has been showcased in the market up until now. One of the biggest pros of vidofludimus calcium is its anti-viral activity. Before now, immunosuppressive therapy has been avoided for fear of JC virus reactivation, a primary cause of progressive multifocal leukoencephalopathy.
According to Dr. Vitt, “the tolerability and safety of vidofludimus calcium have been excellent on the 1,400 patients tested so far.” In Immunic’s past Phase 2 relapsing MS study, most of the patients continue to report benefits from taking vidofludimus calcium. This is an excellent reminder that “the target of the drug is the patient,” and their reaction to how well they are tolerating it offers a future look at combination therapy and its effect on preventing clinical disability. Dr. Vitt adds that “the right combination of drugs will have the biggest impact on preventing disability.” The question then becomes, what is the best way to use it and when should it be started, sequentially or in linear combination?
Immunic is on the precipice of a revolutionary change as IMU-838 is offering hope to MS patients by delivering what has so far been considered unattainable. The impact of vidofludimus calcium goes beyond anti-inflammatory to include neuroprotective and anti-viral effects.
Top-line data from their Phase 2 CALLIPER trial of vidofludimus calcium in PMS is expected in April 2025. This could be a groundbreaking difference, concludes Dr. Vitt. “If the neuroinflammation data is proven, its use could be expanded into indications outside of MS in the future.”
