Pivotal myasthenia gravis data from argenx augur well for FcRn inhibitors in development
Leading the pack of biotechs vying for a piece of the generalized myasthenia gravis (gMG) market with an FcRn inhibitor, argenx on Tuesday unveiled keenly anticipated positive late-stage data on its lead asset, bringing it one step closer to regulatory approval and lifting its stock by more than a third.
Despite steroids, immunosuppressants, acetylcholinesterase inhibitors, and Alexion’s Soliris, patients with the rare, chronic neuromuscular disorder (more than 100,000 in the United States and Europe) don’t necessarily benefit from these existing options, leaving room for the crop of FcRn inhibitors in development.
Belgium-based argenx’s experimental drug, efgartigimod, was tested against a placebo over 26 weeks in 167 adults with generalized myasthenia gravis (gMG) who were on background gMG therapy in the late-stage study christened ADAPT.
In the study, 67.7% of acetylcholine receptor-antibody positive patients treated with efgartigimod achieved the primary endpoint — the percentage of responders (a responder was defined as ≥2 point improvement for at least 4 consecutive weeks, during the first 8-week period) on a daily living with MG scale — compared with 29.7% on placebo (p<0.0001).
On the secondary goal, 63.1% of those patients responded to efgartigimod compared with 14.1% on placebo on another scale called Quantitative Myasthenia Gravis (QMG) (p<0.0001). Other secondary endpoints, including time on trial in clinically meaningful improvement and fast onset of response, were also found to be statistically significant, although the time to qualify for retreatment endpoint was not met.
“While responder criteria in argenx’s ADAPT trial are slightly different than those utilized in the pivotal trials of Alexion’s Soliris, we broadly view argenx’s top-line data as strong in comparison to the pivotal data from Soliris, and believe this data could position FcRN inhibition as having a significant role …” Baird’s Brian Skorney wrote in a note.
Meanwhile, there were no red flags on the safety side. “Overall, we think the likely speed of onset and definitely the safety of efgartigimod compares extremely well to standard of care therapies, such as IVIG and PLEX, which have rapid onset but are notorious for their safety issues,” Stifel analysts wrote in a note.
Shares of the company $ARGX shot up nearly 33% to $210 on the Nasdaq in Tuesday morning trading.
With these results, argenx plans to submit a marketing application for the IV formulation (60 min infusion) by the end of 2020. If approved, likely by 2021, this version of the product should pave the way for the company’s subcutaneous formulation (packaged as a single ~5 mL injection) to boost commercial prospects. Stifel analysts forecast ~$1.7 billion in peak sales for both efgartigimod formulations for use in MG patients.
Other players with FcRn inhibitors in the pipeline for MG include UCB’s rozanolixizumab (~30 min subcutaneous infusion), Momenta Pharmaceuticals’ nipocalimab (~7.5-15 min IV infusion, with a subcutaneous formulation in development), Immunovant’s IMVT-1401 (two subcutaneous injections of 2 mL each per dose) and Alexion’s ALXN1830 (a subcutaneous infusion that will be tested in a Phase II trial planned for the second half of 202o). Apart from efficacy, the convenience of dosing and duration will play a key role in the adoption of these FcRn therapies, analysts said.
Argenx’s results further validate the anti-FcRn mechanism in MG and bode well for the mid-stage nipocalimab readout expected in the coming weeks, Stifel analysts added on Tuesday.
MG occurs when IgG antibodies disrupt communication between nerves and muscles, causing potentially life-threatening muscle weakness. More than 85% of patients progress to generalized MG (gMG) within 18 months, where muscles throughout the body may be affected, resulting in extreme fatigue and difficulties with facial expression, speech, swallowing and mobility.
The need for new treatment options is apparent — given the toxicity of steroids and immunosuppressants and Soliris’ prohibitive costs. While intravenous immunoglobulin (IVIg) is used as a stop-gap, high costs, long infusions accompanied by headaches and supply constraints limit its broader appeal.
“FcRn antagonists’ broadly applicable mechanism of action and safe and efficacious clinical profile should support their competitive edge and support use in earlier lines of therapy. Given efgartigimod’s lead to market and likely availability as both IV and SQ, we anticipate that it will capture the lion’s share of the market,” Cowen analyst Yaron Werber wrote in an April note.
The neonatal Fc receptor (FcRn) plays a key role in preventing the degradation of IgG antibodies. FcRn recycles IgG antibodies by shuttling them away from lysosomal degradation, thereby preserving pathogenic antibody levels in IgG-mediated diseases such as myasthenia gravis (a long-term condition). Drugs designed to inhibit FcRn, therefore, are designed to decrease total IgG — crucially pathogenic IgG — to treat patients.
Social image: argenx