Camurus AB and Ra Pharmaceuticals have signed an agreement to develop and manufacture a long-acting injectable formulation of zilucoplan for patients with complement-mediated disorders, such as generalized myasthenia gravis.
Using Camurus’s proprietary FluidCrystal technology, the subcutaneously injected formulation will allow patients with complement-mediated disorders — such as generalized myasthenia gravis and immune-mediated necrotizing myopathy — to administer zilucoplan once weekly.
“The FluidCrystal extended-release formulation of zilucoplan has the potential to control disease for at least seven days from a single subcutaneous dose without the need for intravenous loading, on-body infusion devices, tissue-degrading enzymes, or permeation enhancers,” Doug Treco, PhD, president and CEO of Ra Pharma, said in a press release.
Zilucoplan, formerly known as RA101495, is a synthetic small molecule that was specifically designed to bind and inhibit the activity of complement 5 (C5).
C5 is one of the many proteins that belong to the complement system, which forms part of the body’s immune defenses and is believed to contribute to the production of harmful autoantibodies in myasthenia gravis patients.
Data from a Phase 2 clinical trial (NCT03315130) showed that zilucoplan administrated at a daily dose of 0.3 mg/kg by subcutaneous (under the skin) injection could induce significant reductions in the quantitative MG score — a measure of myasthenia gravis severity.
The trial also found that none of the zilucoplan-treated patients required additional rescue therapy — either with intravenous antibodies or plasma exchange — to manage their symptoms, compared with 20% (three of 15) of the placebo-treated patients.
Based on these promising clinical results, researchers decided to develop an extended-released version of zilucoplan to reduce the burden of having to administer the medication daily.
Zilucoplan XR will use Camurus’ FluidCrystal injection depot, which transforms from a fatty liquid into a crystalline gel upon contact with the fluid in body tissues. This gel effectively encapsulates the active therapeutic ingredient and allows it to be slowly released as the gel gradually degrades in tissue, according to the company.
“The partnership with Ra Pharma follows the successful completion of a feasibility study of the FluidCrystal extended release zilucoplan injection, which met formulation, pharmacokinetic, and tolerability target specifications,” said Fredrik Tiberg, president and CEO of Camurus.
Preclinical studies in primates showed that a single dose of zilucoplan XR could induce rapid and sustained complement inhibition at therapeutic levels for at least seven days. During this time, additional intravenous administrations of the therapy were not required to achieve nearly complete inhibition of C5.
Data showed that zilucoplan XR delivered at 0.3 mg/kg once weekly produced similar activity to that of the simpler zilucoplan formulation administrated daily at 0.3 mg/kg. This demonstrates that the new formulation may achieve the same therapeutic activity with less-frequent dosing.
“The promising data from our preclinical studies conducted with Camurus, the potential for cost-effective manufacturing, and Camurus’s proven late-stage regulatory experience with FluidCrystal were compelling reasons to add the FluidCrystal technology into our zilucoplan XR life-cycle extension program,” Treco said.