#AAN2018- Ra Pharma’s Myasthenia Gravis Therapy Shows Promise in Phase 1 Trial with Healthy Volunteers

Ra Pharma’s RA101495, a potential treatment for generalized myasthenia gravis patients, showed preliminary signs of halting red blood cell destruction in healthy volunteers, results of an early clinical trial show — justifying the Phase 2 trial in patients now underway.

Data reporting on the Phase 1 trial results — showing that RA101495 led to a rapid and sustained drop in hemolysis,  or cell rupture — will be presented at the annual meeting of the American Academy of Neurology in Los Angeles on April 25.

James F. Howard Jr., M.D., a medical professor at the University of North Carolina, will lead the oral presentation, “RA101495, A Subcutaneously Administered Peptide Inhibitor of Complement Component 5 (C5) for the Treatment of Generalized Myasthenia Gravis (gMG): Phase 1 Results and Phase 2 Design.”

These results prompted Ra Pharma to start a Phase 2 trial of RA101495 that continues to enroll myasthenia gravis patients. Those participating in the trial will self-administer the therapy via injections.

In the Phase 1 trial, the volunteers received single or  multiple doses for seven days, and tolerated the treatment well, the study reports.

RA101495 led to a 95 percent drop in complement destruction of red blood cells within three hours of the first dose. The effect lasted more than 24 hours in the higher-dosed groups.

Findings supported “the evaluation of RA101495 in a Phase 2 study” in generalized myasthenia gravis, the researchers said.

The 12-week Phase 2 trial (NCT03315130) is evaluating the safety and preliminary effectiveness of RA101495, and patients’ ability to tolerate it. Researchers’ aim is to recruit 36  generalized myasthenia gravis patients at sites across the U.S. and Canada.

Participants will be randomly assigned to one of two doses of RA101495 — either 0.1 mg/kg or 0.3 mg/kg — or a placebo daily.

The trial’s main objective is to see whether the treatment can improve patients’ scores on the  Quantitative Myasthenia Gravis scale. A secondary objective is to see if it can improve their ability to engage in daily activities. The measurement for this will be patients’ scores on the Myasthenia Gravis-Activities of Daily Living scale.

Enrollment is continuing in the Phase 2 trial, which is expected to conclude in early 2019. More information is available here.

RA101495 “potently inhibits C5 [complement component 5], a validated therapeutic target in myasthenia, and offers a convenient, once-daily, subcutaneous, self-administration regimen that has the potential to benefit a broad population of gMG [generalized myasthenia gravis] patients,” Ramin Farzaneh-Far, the chief medical officer of Ra Pharma, said in a press release.

“Subcutaneous [under-the-skin] self-administration of RA101495, if shown effective, may not only enable a broader population of gMG patients to potentially benefit from targeted C5 inhibitor therapy but also ease the treatment-related burden of intravenous options,” the researchers wrote.

“We continue to work toward rapid enrollment of this Phase 2 trial, with the goal of reporting top-line data [key results] in the first half of 2019, and to advance” RA101495 to a Phase 3 trial in the second half of 2018, Farzaneh-Far said.