Just about one month ago, clinical-stage biotechnology company AnaptysBio announced the availability of positive top-line results from two Phase 3 clinical studies: GEMINI-1 and GEMINI-2. Both studies sought to assess how safe, well-tolerated, and effective imsidolimab was in treating individuals with generalized pustular psoriasis (GPP). Ultimately, the investigational IgG4 antibody performed well in the clinical setting.
Imsidolimab in Clinical Trials
AnaptysBio describes imsidolimab as a fully humanized monoclonal antibody therapy:
That inhibits the function of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogenesis of inflammatory diseases, including GPP.
45 participants enrolled in the Phase 3 GEMINI-1 study. During the course of the study, participants received either a placebo, 300mg intravenously administered imsidolimab, or 750mg intravenously administered imsidolimab as a one-time dose. The study found that 13% of people on the placebo achieved clear or nearly clear skin by the fourth week, compared to 53% in both the 750mg and 300mg groups. Imsidolimab was tolerated well by participants and did not increase infection or infusion site reaction rates.
42 participants were re-randomized into the GEMINI-2 study, where they were split into groups that either received 200mg subcutaneously administered imsidolimab for maintenance or a placebo. Participants were monitored for 24-92 weeks. Of the 16 participants who had achieved clear or nearly clear skin in the first trial, 50% (those taking the imsidolimab maintenace dose) experienced no flares during the second trial. The remaining 50% (those taking the placebo) had more complicated results. While some still maintained clear skin, a majority of these individuals experienced a GPP flare. This suggests that imsidolimab not only initially clears skin but can prevent flares over time.
Moving forward, AnaptysBio plans to submit and possibly present data from these studies, as well as out-license imsidolimab, later this year.
Know the Facts: Generalized Pustular Psoriasis (GPP)
Also known as: von Zumbusch psoriasis
Generalized pustular psoriasis is a rare and severe form of psoriasis, a skin disorder. It can occur in people of all ages but is more likely to happen in adults. When GPP occurs in children, it is commonly linked to genetic mutations like IL36RN. GPP affects women more than men and tends to also happen in people with plaque psoriasis.
As the National Psoriasis Foundation explains, people with GPP experience “flares” that last for weeks at a time. During these flares:
Pustules often cover large areas of the body and typically [present] with fever, shivers, intense itching, a rapid pulse, fatigue, headache, nausea, muscle weakness, and joint pain.
Additional symptoms can include anorexia, conjunctivitis or uveitis, jaundice, nail abnormalities, and lower limb edema. GPP flares can be triggered by stress, infections, menstruation, corticosteroid withdrawal, and pregnancy. When they occur during pregnancy, flares are more likely in the third trimester. Without treatment, flares can be life-threatening and cause severe complications, such as bacteremia or septicemia, metabolic disturbances, or cardiac failure.
DermNet explains that treatments should occur promptly, and many individuals require hospitalization. Treatment may include pain relievers, IV fluids, moisturizers, topical calcipotriol or tacrolimus, phototherapy, antibiotics, non-biologics, and biologics like IL-23 or IL-17 antagonists. Your doctor can help identify the best line of treatment for you.
