Argenx's autoimmune phase 3 hits goals, teeing up FDA filing

A phase 3 trial of Argenx’s efgartigimod in generalized myasthenia gravis (gMG) patients has hit its primary endpoint, setting the European biotech up to file for FDA approval by the end of the year.

Efgartigimod is an antibody fragment designed to bind to neonatal Fc receptor (FcRn), driving down levels of antibodies implicated in multiple autoimmune diseases. The potential of FcRn has attracted the attention of drug developers including Alexion, Immunovant and UCB, but Argenx is the first to validate the target with phase 3 data.

The trial randomized 167 adults with gMG, a disease that causes loss of muscule function, to receive infusions of efgartigimod or placebo for 26 weeks. Over that period, efgartigimod outperformed the control against a clutch of endpoints.

In the efgartigimod arm, 67.7% of acetylcholine receptor (AChR)-antibody positive patients met the criteria for a response to the drug, compared to 29.7% of people in the placebo cohort, causing the trial to hit its primary endpoint. There were statistically more responders in a broader population including AChR-antibody negative patients, too. 

Efgartigimod also outperformed placebo against secondary endpoints. Using a different gMG disease scale, 63.1% of patients on the experimental drug were classed as responders, compared to 14.1% in the control group. Another analysis found 40% of people in the efgartigimod arm had disease scores of 0, indicating they were symptom free, or 1. In the placebo group, 11.1% of patients had symptoms that mild. 

Subjects receiving efgartigimod also experienced faster relief from symptoms, as measured by time to clinically meaningful improvement and onset of response. The only disclosed efficacy setback was the failure of the time to qualify for retreatment endpoint to meet statistical significance.

With the study finding efgartigimod has a safety profile comparable to placebo, Argenx is gearing up to file for FDA approval by the end of the year. If efgartigimod comes to market, Argenx sees it being used to enable physicians to start tapering steroids sooner and delay or eliminate the need for broad immunosuppressants. Alexion’s Soliris is used later in the disease pathway.

The data presented today have implications beyond Argenx’s efforts to win approval in gMG. Argenx is studying efgartigimod in three indications other than gMG and plans to disclose a fifth indication soon. The phase 3 data add to evidence that efgartigimod can play a role in autoimmune diseases.  

Argenx’s phase 3 data also set a bar for rival FcRn assets in gMG. Alexion acquired anti-FcRn antibody ALXN1830 in its $400 million takeover of Syntimmune and is gearing up to test the drug in a phase 2/3 trial of gMG patients. UCB moved its FcRn prospect rozanolixizumab into a phase 3 gMG trial last year but then temporarily suspended enrollment in response to COVID-19. A far smaller phase 2 trial of Immunovant’s IMVT-1401 is continuing, according to 

Shares in Argenx rose almost 30% in premarket trading on news of the phase 3 success.