Multiple sclerosis treatments have come a long way since the first drug received approval in 1993. In the 31 years since, advances have come in waves, including a 2017 approval of the first treatment for primary progressive multiple sclerosis.
But when it comes to safety, none of these advances are perfect.
“Every current treatment has a bit of a drawback,” said Daniel Vitt, CEO of Immunic Therapeutics, a clinical-stage biotech company developing therapies for chronic inflammatory and autoimmune diseases.
Some MS drugs, including Biogen’s Tysabri, are associated with the often-fatal brain disease progressive multifocal leukoencephalopathy. Others come with side effects that require regular monitoring of heart or kidney function, which is burdensome for both patients and physicians.
Immunic’s lead candidate, vidofludimus calcium, has not only shown a “benign” safety and tolerability profile in clinical trials, but also antiviral effects, including against COVID-19.
Moreover, the molecule has anti-inflammatory and neuroprotective features that slow down disease progression, prevent relapses and keep patients physically independent longer, according to Immunic.
“Disability worsening is the main unmet medical need,” Vitt said.
The first-in-class vidofludimus calcium activates the target Nurr1, a neuroprotective transcription factor. It’s in phase 3 trials in relapsing MS, a phase 2 trial in progressive MS and a phase 2 trial in relapsing-remitting MS that’s currently in open-label phase.
“This neuroprotective feature related to Nurr1 is new, and this could be a game changer for MS patients,” Vitt said.
Three-fold effects
MS is a progressive, neurodegenerative autoimmune disease that attacks the central nervous system. It’s unpredictable, comes in a variety of forms and progresses differently in every patient, but always involves two primary pathological processes: Focal inflammation and neurodegeneration.
“People say it has a thousand faces, and every individual case may be a little bit different, but the overall pattern is the same,” Vitt said. “Both processes lead to destruction of neural tissue and loss of physical ability of the patients.”
That’s why vidofludimus calcium’s three main features — anti-inflammation, neuroprotection and antiviral effects — are so important.
First, there are the inflammatory processes that contribute specifically to MS relapse.
“Our drug, with its mode of action targeting a protein in the metabolic pathway called DHODH, is very good [at] preventing inflammation,” Vitt said.
Immunic’s phase 2 study showed this effect reduces inflammatory lesions in the brain, as measured by MRI, and reduces relapses.
Second is the neuroprotection related to activating Nurr1, “which is known to play an important role in protecting neurons from cell death,” Vitt said. Nurr1 is also a potential target for Parkinson’s disease, and activating the receptor has shown protected relevant neurons from cell death, slowing down disability for patients in clinical trials.
“This is the big differentiator. I’m not aware of any other MS drug acting on Nurr1,” Vitt said. “Therefore I think this drug, by being a Nurr1 activator, can really make a difference from the current standard of care.”
Third is the antiviral piece. Research has shown that infection with the Epstein-Barr virus (EBV) leads to a 32-times higher likelihood of developing MS.
“One of the causes of the disease is an infection with EBV,” Vitt said. “It is one ingredient in a big equation of why patients get multiple sclerosis.”
Vidofludimus calcium has potent anti-EBV activity and the potential to suppress EBV-related T cells. In clinical trials, this combination of factors has resulted in patients staying independent longer, slowing down the progression of the disease and staving off disability, which is often what matters most to patients, Vitt said.
Easier to use
In addition to its clinical benefits, vidofludimus calcium’s safety profile is another factor in its status as a potential MS game changer.
“I think that’s one of the big strengths of that molecule,” Vitt said.
In more than 1,800 people in clinical trials, the drug’s side effect profile has been very similar to the placebo profile, with no liver enzyme differences observed between the treatment and placebo groups. There were also no cardiovascular findings and no infection risk increase.
That means it could be an easier treatment on both patients and physicians, without the need for expensive and cumbersome screening and monitoring. That’s also different from many other MS drugs in development, such as Bruton's tyrosine kinase (BTK) inhibitors, which are associated with liver injury.
“What I learned from doctors is they want to have an easy treatment,” Vitt said.
Vitt said the company expects a readout for its phase 2 data in progressive MS in April 2025 — which will help determine how well the drug protects the brain — and results for its phase 3 studies the following year.
Vitt said that in talking with patients and physicians, slowing disability progression is key.
“With multiple sclerosis they lose, over time, their independence,” he said. “That’s the biggest threat to patients today.”
