IL-36R

Boehringer Ingelheim’s Spevigo (spesolimab) injection has been recommended by the European Medicines Agency’s committee for human medicines as a new indication for the prevention of generalised pustular psoriasis (GPP). The injection has been recommended to prevent GPP flares in adults and adolescents from 12 years of age, as well as the extension approval of Spevigo infusion to treat GPP flares in adults and adolescents from 12 years of age as a monotherapy. Recognised as a separate clinical entity from other forms of psoriasis, GPP is a chronic, heterogeneous, neutrophilic inflammatory disease that is associated with skin and systemic symptoms distinct from plaque psoriasis and can sometimes lead to multiple complications, including multisystem organ failure and sepsis. Already approved in 51 countries, including the EU , US and China, Spevigo is a novel, humanised selective IgG1 antibody that binds to the interleukin-36 receptor, a key part of a signalling pathway within the immune system shown to be associated with GPP. The Committee for Medicinal Products for Human Use’s decision was based on positive results from the 48-week phase 2b EFFISAYIL 2 clinical trial, as part of the EFFISAYIL clinical programme combining EFFISAYIL 1, a phase 2 study, EFFISAYIL ON, an open-label extension study and the ongoing EFFISAYIL REP open-label, phase 3b/4 trial. Results from the phase 2b trial showed that Spevigo significantly reduced the risk of GPP flares by 84% in 123 patients compared with placebo and no flare-ups were observed in patients from the high-dose group with Spevigo subcutaneous treatment after week four. In addition, the trial showed a consistent incidence of patients with adverse events across the Spevigo and placebo treatment arms. Commenting on the recommendation, Carinne Brouillon, head of human pharma at Boehringer, said: “The CHMP’s positive opinion on Spevigo… signals a strong shift in treatment, offering people living with [GPP] the potential for significant improvement of their condition and a better quality of life.” The company recently announced its acquisition of Nerio Therapeutics for up to $1.3bn, expanding its immune-oncology pipeline by gaining access to its small molecules designed to inhibit the protein tyrosine phosphatases N1 and N2.

The CHMP positive opinion is based on the EFFISAYIL® 2 trial, which showed that no flares were observed after week 4 of SPEVIGO® administered subcutaneously. During the 48-week trial, an 84% reduction of the risk of GPP flares was observed.GPP is a rare, chronic, heterogenous neutrophilic inflammatory disease associated with skin flares and systemic symptoms, such as fever, pain, and fatigue.SPEVIGO® is currently approved in 51 countries for treatment of GPP flares, and the CHMP opinion follows similar approvals for expanded and new indications in the US and China. Boehringer Ingelheim today announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended approval of a new indication of SPEVIGO® (spesolimab) injection for the prevention of generalized pustular psoriasis (GPP) flares in adults and adolescents from 12 years of age; and extension of the approved indication for SPEVIGO® (spesolimab) infusion for the treatment of generalized pustular psoriasis (GPP) flares in adults and adolescents from 12 years of age as monotherapy. SPEVIGO® is a novel, humanized selective IgG1 antibody that binds to interleukin-36 receptor (IL-36R), a key part of a signaling pathway within the immune system shown to be involved in the cause of GPP. The regulatory authorities’ decisions are based on the positive results of the EFFISAYIL® 2 trial, a 48-week clinical trial that showed that SPEVIGO® significantly reduced the risk of GPP flares by 84%, compared with placebo. In the trial with 123 patients, no flares were observed after week 4 of SPEVIGO® subcutaneous treatment in the high-dose group (n=30). The EFFISAYIL® 2 trial showed a similar incidence of patients with adverse events across spesolimab and placebo treatment arms. “GPP presents a significant diagnostic challenge for healthcare professionals as it is a highly variable rare disease that is experienced differently by everyone who has it, and it has suffered from a historic lack of treatment options,” said Dr Peter van der Kerkhof, Professor and previous Chairman of the Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. “Spesolimab’s recent approvals, combined with the CHMP recommendation provides us with the potential for continuous treatment, addressing a significant unmet need.” Distinct from plaque psoriasis, GPP is a rare, chronic, heterogenous, inflammatory neutrophilic disease associated with painful skin manifestations and systemic symptoms, such as fever, pain, and fatigue. GPP varies widely between individuals living with the condition, with symptoms presenting both above and below the skin. Uncontrolled GPP may require emergency care and can lead to life-threatening complications, such as multi-organ failure and sepsis. GPP’s unpredictable nature can potentially have significant long-term impacts on quality of life for people living with it and leads to fear and anxiety over the disease course. “The CHMP’s positive opinion on SPEVIGO®, alongside approvals in China and the US, signals a strong shift in treatment, offering people living with the disease the potential for significant improvement of their condition and a better quality of life,” said Carinne Brouillon, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “The potential to prevent GPP flare-ups means a possibility to gain back control over how people affected by the disease live their lives.” "GPP goes way beyond the skin, it's a relentless and unpredictable disease that can impact every aspect of a person's life,” said Frida Dunger, Executive Director, IFPA (International Federation of Psoriasis Associations). “I want a world where every person with GPP is diagnosed quickly and receives the treatment they need, and this is their right. There is much more to do, but I believe with all stakeholders working together we are headed in the right direction.” About SPEVIGO®SPEVIGO® is a novel, humanized, selective antibody that specifically blocks the activation of the IL-36R, a signaling pathway within the immune system shown to be involved in the pathogenesis of several autoinflammatory diseases, including GPP. It is the first targeted therapy for the treatment of GPP and has been evaluated in the largest clinical program specifically for the treatment of patients with GPP. About generalized pustular psoriasis (GPP)GPP is a chronic, heterogenous, neutrophilic inflammatory disease associated with skin and systemic symptoms that is distinct from plaque psoriasis. GPP is recognized as a separate clinical entity from other forms of psoriasis, with the IL-36 pathway being a key driver of GPP and triggering response to treatment. Prevalence of GPP varies considerably across geographical regions, ranging from 1.76 to 124 patients per million persons. GPP can become life-threatening (mortality rates ranging from 2% to 16%) due to severe complications, such as multisystem organ failure and sepsis requiring urgent hospital care; many GPP patients also suffer from various comorbidities, which contribute to the ongoing burden for the patient and healthcare systems. GPP symptoms appear unpredictable and present on a continuum, which greatly impacts a patient’s quality of life, and may cause fear and anxiety over the disease course, as well as long-term impacts on quality of life related to work/school, emotional health, social activities, and finances. About the EFFISAYIL® clinical trial programThe EFFISAYIL® clinical trial program evaluated the largest and broadest population of GPP patients in trials of a therapy specifically targeting the IL-36 pathway for GPP. EFFISAYIL® 1: A Phase II study that demonstrated treatment with a single intravenous dose of spesolimab significantly improved signs and symptoms of GPP in patients experiencing a flare, including rapid pustular and skin clearance. These results supported the approval of spesolimab as the first specific treatment for GPP flares in adults in major markets.EFFISAYIL® 2: A Phase IIb study that showed subcutaneous spesolimab significantly reduced the risk of GPP flares by 84% over 48 weeks compared to placebo. In the trial with 123 patients, no flares were observed after week 4 of spesolimab SC treatment in the high-dose group (n=30). EFFISAYIL® ON: An open-label extension study to evaluate the long-term safety and efficacy of spesolimab in patients with GPP who have completed previous spesolimab trials. EFFISAYIL® REP (ongoing): An open-label, single-arm, Phase IIIb/IV trial to evaluate the efficacy, safety, and the impact of immunogenicity in the treatment of patients with GPP presenting with a recurrent flare following their initial GPP flare treatment with spesolimab IV. About Boehringer IngelheimBoehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at https://www.boehringer-ingelheim.com/.

All eight patients from GEMINI-1 who responded to a single intravenous (IV) imsidolimab dose and were subsequently re-randomized to monthly subcutaneous (SC) maintenance dosing of imsidolimab in GEMINI-2 through at least 24 weeks maintained clear to almost clear skin and none experienced a flare Of the remaining eight responding patients from GEMINI-1 re-randomized to placebo in GEMINI-2, 25% maintained clear to almost clear skin and 63% of these patients experienced a flare Safety and tolerability in GEMINI-2 patients was consistent with reported profile from GEMINI-1 Plan to submit a comprehensive data abstract for GEMINI-1 and GEMINI-2 to a H2 2024 medical meeting Intend to out-license imsidolimab in 2024 May 09, 2024 -- AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics, today announced positive top-line results from its global GEMINI-1 and GEMINI-2 Phase 3 trials evaluating the safety and efficacy of investigational imsidolimab (IL-36R mAb) in patients with generalized pustular psoriasis (GPP), a severe orphan disease that is potentially life-threatening if left untreated. In the 45-patient GEMINI-1 Phase 3 trial, patients were randomized 1:1:1 to receive a single infusion of 750mg intravenous (IV) imsidolimab, 300mg IV imsidolimab or placebo at Day 0. Of the patients who received a single dose of 750mg IV imsidolimab, 53% achieved a GPP Physician Global Assessment (GPPPGA) score of 0/1 (clear or almost clear skin) at Week 4 (primary endpoint), compared to 13% of the patients on placebo (p=0.0131). Of the patients who received a single dose of 300mg IV imsidolimab, 53% achieved GPPPGA 0/1 at Week 4. Sixteen GPPPGA 0/1 responder patients from GEMINI-1 were subsequently re-randomized to monthly maintenance dosing of either 200mg subcutaneous (SC) imsidolimab or placebo in the GEMINI-2 Phase 3 trial. Patients were followed for at least 24 weeks and up to a maximum of 92 weeks. Of the eight responding patients from GEMINI-1 who were re-randomized to monthly 200mg SC imsidolimab maintenance therapy, 100% maintained a GPPPGA score of 0/1 and none of them experienced a flare. Of the remaining eight responding patients from GEMINI-1 who were re-randomized to placebo, 25% maintained a GPPPGA score of 0/1 and 63% experienced a flare. “The success of the GEMINI-1 and GEMINI-2 Phase 3 trials highlights Anaptys’ ability to internally discover and develop differentiated antibodies that deliver meaningful outcomes for patients,” said Daniel Faga, president and chief executive officer of Anaptys. “The results of these modestly sized studies reinforce that only one single IV dose of imsidolimab was required to achieve rapid clearance of GPP through four weeks and maintained in patients receiving a monthly SC maintenance dose. We remain intent on out-licensing imsidolimab to bring this therapy to patients living with this highly morbid condition.” Data from both trials demonstrate a consistent, favorable safety and tolerability profile with no treatment-related serious adverse events (SAEs) or SAEs leading to discontinuation reported in imsidolimab-treated patients. Additionally, the data show: Low incidence and no elevation of infections versus placebo No cases reported of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or Guillain-Barre syndrome (GBS) No infusion reactions reported Overall incidence of anti-drug antibodies (ADA) was low and, when detected, determined to be non-neutralizing Anaptys plans to submit a comprehensive data abstract for GEMINI-1 and GEMINI-2 results to a H2 2024 medical meeting. With all patients having passed 24 weeks and the furthest patient being treated through 92 weeks, the company is concluding the GEMINI-2 trial. The company plans to out-license imsidolimab in 2024, and a potential future filing of a biologics license application (BLA) with the U.S. Food and Drug Administration (FDA) will be contingent on an out-licensing transaction. “We’re immensely grateful to all the study investigators, study staff and trial participants who helped evaluate this potential new treatment option for GPP,” said Paul Lizzul, M.D., Ph.D., chief medical officer of Anaptys. “We’re pleased that we have generated clinically meaningful data to support a potential future regulatory submission.” Anaptys’ first Phase 3 GEMINI-1 clinical trial was a four week, double-blind, placebo-controlled, randomized study to evaluate the efficacy and safety of imsidolimab in patients with GPP, irrespective of mutational status. A total of 45 patients, 15 patients per arm, were enrolled across diverse global regions ranging from the U.S., EU, MENA, and Asia. Patients were randomized 1:1:1 to receive a single infusion of 750mg IV imsidolimab, 300mg IV imsidolimab or placebo at Day 0. The objective of the GEMINI-2 trial was to assess the safety and efficacy of imsidolimab for maintenance of response, and the prevention of GPP flares with monthly SC dosing. A total of 42 patients were subsequently re-randomized into GEMINI-2. The 16 GPPPGA 0/1 responder patients from GEMINI-1 were re-randomized 1:1 to receive either monthly SC maintenance therapy of 200mg imsidolimab or placebo. Imsidolimab is a fully humanized IgG4 antibody that inhibits the function of the interleukin-36-receptor, or IL-36R, that is being developed for the treatment of GPP. GPP is a rare, chronic, systemic autoinflammatory disease that is potentially life-threatening if left untreated. During a GPP flare, individuals experience the sudden eruption of painful pustules. These pustules appear over large areas of the skin, accompanied by redness, severe itchiness, and dry, cracked or scaly skin. People with GPP may also experience more general symptoms such as fever, headache, extreme tiredness or a burning sensation on the skin. Anaptys is a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics. It is developing immune cell modulators, including two checkpoint agonists for autoimmune and inflammatory disease: ANB032, its BTLA agonist, in a Phase 2b trial for the treatment of atopic dermatitis and rosnilimab, its PD-1 agonist, in a Phase 2b trial for the treatment of rheumatoid arthritis and in a Phase 2 trial for the treatment of ulcerative colitis. Its preclinical immune cell modulator portfolio includes ANB033, an anti-CD122 antagonist antibody, and ANB101, a BDCA2 modulator antibody, for the treatment of autoimmune and inflammatory diseases. In addition, Anaptys has developed two cytokine antagonists available for out-licensing: imsidolimab, an anti-IL-36R antagonist that has completed Phase 3 trials for the treatment of generalized pustular psoriasis, and etokimab, an anti-IL-33 antagonist that is Phase 2/3 ready. Anaptys has also discovered multiple therapeutic antibodies licensed to GSK in a financial collaboration for immuno-oncology, including an anti-PD-1 antagonist antibody (Jemperli (dostarlimab-gxly)) and an anti-TIM-3 antagonist antibody (cobolimab, GSK4069889). To learn more, visit www.AnaptysBio.com or follow us on LinkedIn and X. The content above comes from the network. if any infringement, please contact us to modify.