Weekly Dosing with Extended Release Zilucoplan Shows Similar Activity as Daily Dose

A new extended release formulation of zilucoplan, a potential self-administered therapy for patients with generalized myasthenia gravis (gMG), given once weekly, achieved complement 5 (C5) inhibition similarly to zilucoplan administered daily, pre-clinical data in non-human primates show.

Zilucoplan, developed by Ra Pharmaceuticals, is an artificial peptide that binds to C5, inhibiting its activity and preventing the overactivation of the complement system — a set of more than 50 blood proteins that form part of the body’s immune defenses — which is thought to be involved in the formation of harmful autoantibodies in MG.

Data from a Phase 2 clinical trial showed that zilucoplan at a daily dose of 0.3 mg/kg injected subcutaneously (under the skin) led to a statistically significant reduction in the quantitative MG (QMG) score of 6.0 points and 3.4 points in the MG-ADL score, relative to the beginning of the study and compared to the placebo group (2.8 points and 2.3 points, respectively).

Moreover, none of the patients treated with zilucoplan at 0.3 mg/kg required rescue therapy (either with intravenous antibodies or plasma exchange), compared to 20% (three of 15) of the patients in the placebo group.

The extended released version of zilucoplan uses poly (D,L-lactic-co-glycolic acid) (PLGA) technology, an established delivery platform for sustained release of peptides.

The new results showed that the extended release formulation of zilucoplan delivered at 0.3 mg/kg once weekly had similar activity to that of 0.3 mg/kg delivered daily.

“We’re excited to present data for the PLGA XR formulation of zilucoplan, in which target drug concentrations were achieved and maintained with once-weekly subcutaneous dosing,” Simon Read, PhD, chief scientific officer of Ra Pharma said in a press release.

“Our XR [extended release] development program allows for simple administration of a low drug volume without the need for intravenous loading, on-body infusion devices, tissue-degrading enzymes, or permeation enhancers,” he said.

Zilucoplan levels also were maintained for 14 days, along with an almost complete inhibition of C5.

Overall, this means the new formulation may achieve the same therapeutic activity with less-frequent dosing.

These results were presented at the 6^th Annual Peptides Congress April 24-25 in London in a presentation titled, “Development of a Pipeline of Macrocyclic Peptides for Disorders of the Complement System.”

“Consistent with our patient-centric approach to drug development, the progress of the PLGA XR formulation of zilucoplan is an important step in our efforts to develop and expand patient access to simple and convenient treatment options for a wide range of C5-mediated diseases,” said Doug Treco, PhD, president and CEO of Ra Pharma.

Ra Pharmaceuticals is preparing a Phase 3 clinical trial to continue assessment of the therapeutic potential of zilucoplan, delivered at a daily dose of 0.3 mg/kg by subcutaneous (under the skin), for gMG patients.

“We look forward to sharing our continued progress in this and other XR formulations that form part of the zilucoplan life-cycle extension program, and we remain on track to advance the zilucoplan XR program into the clinic in the first half of 2020,” said Read.