The approval of Roche Holding AG's Ocrevus (ocrelizumab) last month made it the first FDA-approved multiple sclerosis (MS) drug that provided benefit to patients with primary progressive MS. (See BioWorld Today, March 30, 2017.)

At the American Association of Neurology annual meeting, which starts in Boston Saturday, researchers are presenting various studies suggesting that a similar success may be at hand in secondary progressive MS (SPMS).

MS is an autoimmune reaction to the myelin sheath that insulates neurons and makes high-speed neuronal communication possible. In most patients, it begins as a relapsing-remitting disease, where bouts of symptoms alternate with periods of complete or near-complete recovery.

Roughly 15 percent of patients have what is known as primary progressive MS (PPMS), where there is no initial period of intermittent reprieve, with disease symptoms worsening steadily from the time of diagnosis. Relapsing-remitting MS ultimately converts to SPMS, where the symptoms no longer improve between relapses.

SPMS is particularly challenging, neurologist Michael Racke told BioWorld Today, because "we can stop the inflammation, but we can't really stop the combination of inflammation and already significant damage to the brain. . . . It's sort of like you are putting aging on top of that equation."

As a result, "every drug I can think of that got approved for relapsing MS didn't work in secondary progressive MS."

There is one drug that is approved specifically for the treatment of SPMS, namely Novantrone (mitoxantrone concentrate for injection, Amgen Inc.). But its toxicity precludes long-term use.

Last fall, Novartis AG reported that its siponimod (BAF-312) slowed progression in patients with SPMS in the phase III Expand study. (See BioWorld Today, Aug. 26, 2016.)

Extended efficacy data from the Expand trial will be presented at the Clinical Trials Plenary Session on Monday.

The conference will also see updates on the open-label extension of the phase III ASCEND trial, which is reporting "clinically meaningful benefits . . . on disability progression in advanced SPMS patients," in patients treated with Tysabri (natalizumab, Biogen Inc.), according to its abstract, and on Innate Immunotherapeutics Ltd.'s MIS-416.

And in the emerging science program, researchers are presenting interim results from a phase I trial showing that treating MS patients with T cells trained to attack Epstein-Barr virus (EBV)-infected B cells may be a new approach to the disease that could work in patients with progressive MS.

Researchers from the University of Queensland in Brisbane, Australia, reported on data from six progressive MS patients treated with autologous ATA-188 (Atara Biotherapeutics Inc.).

ATA-188 consists of T cells that have been trained to attack EBV antigens.

There is evidence that an inappropriate immune response to EBV is important in setting off MS, and that B cells and plasma cells that are chronically infected with EBV accumulate in the brain and contribute to the immune attacks on the myelin sheath that are the pathological hallmark of MS.

Though the study's goal is to evaluate the safety of ATA-188, the authors also saw improved symptoms in three of the six patients treated so far.

Of the three patients whose symptoms improved after treatment with ATA-188, two had SPMS, while one had PPMS.

Racke, who treats patients with MS at the Ohio State University Wexner Medical Center and was an investigator in the trial that led to the approval of Ocrevus, said that the approach is interesting, but the question is how specific the EBV approach will turn out to be.

100 percent of patients with MS show evidence of EBV exposure, but "the problem is that 95 percent of the general population has had exposure to that virus. . . . The issue becomes, is there really any specificity," he said.

Chris Haqq, Atara Bio's executive vice president of research and development and chief scientific officer, said the clinical improvements seen in the patients themselves "support the hypothesis that targeting EBV-positive B cells and plasma cells may be an effective therapeutic strategy in the treatment of MS."

The company expects to initiate an additional trial in the second half of 2017.