Hidradenitis

Study met primary endpoint of ACR50 at 16 weeks versus placebo with high statistical significance and is expected to be the first of two registrational trials in psoriatic arthritis Robust clinical responses achieved for the high hurdles of ACR70, PASI100, as well as composite endpoints ACR50/PASI100 and Minimal Disease Activity Favorable safety profile consistent with the IL-17A class and previous izokibep experience March 11, 2024 -- ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today announced its global Phase 2b/3 clinical trial of izokibep in psoriatic arthritis (PsA) met the primary endpoint of ACR50 at week 16 with high statistical significance. Results from the 160 mg weekly (QW) and every other week (Q2W) arms showed improved magnitude of responses on higher hurdle endpoints such as ACR70, PASI100, and Minimal Disease Activity relative to the Phase 2 80 mg Q2W dose. This is notable given a higher baseline disease burden in the Phase 2b/3 trial population relative to the Phase 2 trial. Izokibep was well-tolerated with a favorable safety profile consistent with previous experience and the IL-17A class, without evidence of the safety liabilities observed with targeting IL-17A&F. The trial had a low study discontinuation rate of Pre-specified analyses continue to support the potential for differentiation in enthesitis resolution. Consistent high magnitude absolute responses were demonstrated in the Phase 2-comparable population (baseline Leeds Enthesitis Index (LEI) 1 or 2) although enthesitis resolution overall was not statistically significant due to high placebo response. Izokibep achieved clinically meaningful resolution in patients with the highest burden of enthesitis (baseline LEI 3-6) relative to placebo an effect not previously reported by other agents. Additional information about these results can be found at ACELYRIN.com. Further data from this trial will be presented at future scientific meetings. “These positive Phase 2b/3 data reinforce the potential demonstrated in Phase 2 for izokibep to provide meaningful benefit in treating the debilitating signs and symptoms of active psoriatic arthritis in the joints and skin, as well as enthesitis where the results in the most severe patients are encouraging and warrant further study,” said Philip Mease, MD, MACR, Director of Rheumatology Research at Swedish Medical Center. “We have observed from the Phase 2 46-week data that there is no safety limitation to long-term treatment with izokibep and that longer duration of therapy demonstrated the potential for even further improvements over time.” “We are excited about our continued progress with izokibep in both PsA and HS,” said Shao-Lee Lin, MD, PhD, Founder and CEO of ACELYRIN. “The positive PsA study results at week 16 and the magnitude of responses give us conviction that 160 mg Q2W delivers higher clinical responses than those reported by the approved IL-17A agents, and responses comparable to those reported by the IL-17A&F agents without the associated safety liabilities. Across indications, we have observed clinically meaningful and potentially differentiated benefit from izokibep. We have consistently seen responses in high order efficacy measures such as ACR70 and PASI100 in PsA and HiSCR100 in HS that move patients toward disease resolution. This reinforces our enthusiasm for developing izokibep as an important potential new medicine for patients.” The Phase 2b/3 clinical trial (NCT05623345) is a global, multi center, randomized double-blind, placebo-controlled, trial evaluating the safety and efficacy of izokibep dosed subcutaneously 160 mg every week (QW) or every two weeks (Q2W) and 80 mg every four weeks (Q4W) versus placebo. 351 adult patients with active PsA were enrolled across 71 sites in the United States and Europe and randomized across the four arms. Dose sequencing in the 160 mg Q2W and 80 mg Q4W arms was impacted by a third-party programming error. The range of pharmacokinetic data from both the 160 mg QW and Q2W arms in PsA demonstrated comparable exposures to the same dose levels from the Phase 2b HS study. Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease characterized by multiple manifestations including joint inflammation, skin lesions consistent with psoriasis, and enthesitis (painful inflammation of the small, dense tissues that connect ligament and tendons to bone), all contributing to reduced quality of life. It is estimated that approximately 30% of the 125 million people living with psoriasis worldwide will also develop PsA over time. There remains a large unmet need for more effective therapies to treat PsA across all disease manifestations. Izokibep is a small protein therapeutic designed to inhibit IL-17A with high potency through tight binding affinity, the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody, and an albumin binding domain that extends half-life. Clinical trial data supports the hypothesis that these unique characteristics of izokibep may provide clinically meaningful and differentiated benefits for patients, including resolution of key manifestations of disease. Izokibep is being evaluated in multiple late-stage trials in moderate-to-severe hidradenitis suppurativa (HS), psoriatic arthritis (PsA), and uveitis, with plans to initiate an additional Phase 3 program in axial spondyloarthritis (AxSpA). ACELYRIN, INC. (Nasdaq: SLRN) is a Los Angeles area-based late-stage clinical biopharma company – with additional operations in the San Francisco Bay area – focused on providing patients life-changing new treatment options by identifying, acquiring, and accelerating the development and commercialization of transformative medicines. The content above comes from the network. if any infringement, please contact us to modify.

New Phase 2b results for amlitelimab support potential for best-in-class maintenance of response in atopic dermatitis Late-breaking data at AAD show sustained off-drug improvements of AD signs and symptoms with amlitelimab for 28 weeks The safety profile for patients dosed to 52 weeks was consistent with amlitelimab 24 weeks data showing it to be well-tolerated with no new safety concerns identified Durability of response supports quarterly dosing currently being investigated in Phase 3 pivotal program Sustained biomarker reduction suggests the modulation of immune response and durable disease control via the blockade of OX40L, a non-T cell depleting mechanism Amlitelimab is one of 12 potential blockbusters in Sanofi’s leading immunology pipeline, results for a Phase 2 asthma study expected in H2 2024 and three additional Phase 2 study starts expected by year-end March 11, 2024. Positive results from Part 2 of the investigational amlitelimab Phase 2b study STREAM-AD showed sustained improvement of signs and symptoms for 28 weeks in adults with moderate to severe AD who previously responded to amlitelimab and continued treatment. High responder rates were also observed in participants who were taken off amlitelimab. The safety profile was consistent with Part 1 of the study with amlitelimab being well-tolerated and no new safety concerns identified. These results were presented as part of a late-breaking session at the American Academy of Dermatology (AAD) 2024 Conference in San Diego and support the quarterly (every 12-week) dosing of amlitelimab 250 mg with 500 mg loading dose (LD) now being investigated in a larger Phase 3 clinical program (OCEANA). Director, Professor, Chair of Department of Dermatology and Allergy, University Hospital Schleswig-Holstein “Despite available treatment options, not all patients with moderate-to-severe atopic dermatitis respond sufficiently to these treatments, and many continue to suffer from skin lesions and symptoms such as persistent itch, which can have a high impact on their day-to-day lives. Results from this part of the study indicate amlitelimab’s potential for durable off-drug efficacy which supports the evaluation of a less frequent every 12-week dosing. This could offer an important benefit in the treatment of AD patients.” In the second part of the dose-ranging STREAM-AD study, responders to amlitelimab who achieved a 75% improvement in Eczema Area and Severity Index (EASI-75) score and/or Investigator Global Assessment (IGA) score of 0 or 1 during the 24-week treatment period (Part 1) were re-randomized to explore the maintenance of clinical response over an additional 28-week period with continued amlitelimab treatment or amlitelimab withdrawal. Across all dose arms, patients who continued amlitelimab treatment maintained high EASI-75 and/or IGA 0/1, IGA 0/1, and EASI-75 responder rates through 28 weeks. High responder rates were also demonstrated among patients who were taken off treatment. In 69.2% of patients with continued treatment with amlitelimab 250 mg Q4W with 500 mg loading dose (LD) vs 58.8% of patients withdrawn from treatment IGA 0/1 and/or EASI-75 response was maintained. An analysis including pooled dose-arms showed that IGA 0/1 response was maintained in 71.9% of patients with continued treatment vs 57% of patients withdrawn from treatment. In this analysis, EASI-75 response was maintained in 69% of patients with continued treatment vs. 61.6% of patients withdrawn from treatment. AD-related biomarkers remained reduced at Week 52 in both amlitelimab withdrawn and continuing groups, despite amlitelimab reaching negligible levels in serum. Reduction of TARC, eosinophils, and IL-22 observed at Week 24 was maintained during withdrawal as well as in patients continuing treatment to Week 52. These biomarker data suggest the modulation of inflammatory T cells via the blockade of OX40L and durable control of AD after amlitelimab withdrawal. Head of Global Development, Immunology and Inflammation, Sanofi “It’s unprecedented to see this type of durability of clinical response, which we believe could be very meaningful to patients and is the reason why we selected an every 12-week dosing regimen in the AD pivotal program. AD is a chronic, lifelong disease, which means we must strive to provide a portfolio of solutions to patients that matches their individual needs and puts as little burden on them as possible. We are also moving with speed in our exploration of amlitelimab's potential in 5 other chronic inflammatory diseases, including asthma, hidradenitis suppurativa, scleroderma, celiac disease, and alopecia. In addition, we are exploring 6 other innovative MOAs in 8 dermatologic indications underscoring our commitment to patients with high unmet medical needs.” The aggregated safety profile of amlitelimab in Part 2 of this study was consistent with that of Part 1, with amlitelimab being well-tolerated, and no new safety concerns were identified during the 28-week maintenance/withdrawal period. Overall rates of treatment-emergent adverse events (TEAEs) were 69.8% for continued amlitelimab treatment, 71.9% for the amlitelimab withdrawal-arm and 66.7% for placebo. TEAEs more commonly observed included headache (11.6% amlitelimab continuation, 3.9% amlitelimab withdrawal, 6.7% placebo), upper respiratory tract infection (9.3% amlitelimab continuation, 5.5% amlitelimab withdrawal, 20% placebo). No adverse events such as fever or chills, oral ulcers or conjunctivitis were observed across doses. Amlitelimab is a fully human non-T cell depleting monoclonal antibody that blocks OX40-Ligand, a key immune regulator, and has the potential to be a first- or best-in-class treatment for a range of immune-mediated diseases and inflammatory disorders, including moderate-to-severe atopic dermatitis (Phase 3), asthma (Phase 2), hidradenitis suppurativa (Phase 2), scleroderma, celiac disease, and alopecia (Phase 2 studies to be initiated in 2024). By targeting OX40-Ligand, amlitelimab aims to restore balance between pro-inflammatory and regulatory T cells. Amlitelimab is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority. STREAM-AD, a Phase 2b study, is a randomized double-blind, placebo-controlled study, evaluating amlitelimab in adult patients with moderate-to-severe atopic dermatitis whose disease was inadequately controlled with topical therapies or where such therapies were not advisable. This study is designed with two parts and is double-blind through both. Part 1 was a 24-week treatment period, and Part 2 was a 28-week maintenance/withdrawal period, which included clinical responders from Part 1, defined as participants achieving EASI-75 and/or IGA 0/1 at Week 24. Of 390 participants enrolled in Part 1, 190 entered Part 2. Participants were re-randomized 3:1 to withdraw treatment or continue pre-Week 24 subcutaneous Q4W dose (250mg with 500mg loading dose (LD), 250mg, 125mg, 62.5mg, placebo responders continuing placebo), and were followed to Week 52 for efficacy. The study enrolled 390 people in Australia, Bulgaria, Canada, Czechia, Germany, Hungary, Japan, Poland, Spain, Taiwan, the United Kingdom and the United States. We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. The content above comes from the network. if any infringement, please contact us to modify.

Opzelura is a cream version of Incyte's blockbuster Jakafi. After a pair of approvals in recent years and as its sales continue to climb, Incyte's topical JAK inhibitor Opzelura is adding to its clinical case with trial results that demonstrate its benefits in patients with mild to moderate hidradenitis suppurativa (HS). In a phase 2 study testing twice-daily Opzelura cream in patients with mild to moderate HS, investigators noted a “significantly greater” reduction in patients’ abscesses and inflammatory nodule (AN) count after 16 weeks compared with patients who received a control cream. The disease is characterized by painful nodules and abscesses that can cause irreversible tissue destruction and scarring.  The results, which the company shared in a presentation at this year’s American Academy of Dermatology meeting, show “great potential” for patients with milder HS, Incyte's vice president of inflammation and autoimmunity, Jim Lee, M.D., Ph.D., said in a release. “Despite its daily impact on the lives of patients, there are currently no approved therapies for mild-to-moderate HS and the current standard of care is often inadequate,” Lee added. “Today’s data represent an important step in progressing research for HS with the goal of being able to provide patients with an effective option to better manage their condition.” The drug reduced total AN count by 50% or more in roughly 79% of patients, while more than 20% of patients who received the drug achieved complete clearance. Plus, the majority of Opzelura patients met the criteria for Hidradenitis Suppurativa Clinical Response, a measure that includes a 50% or greater reduction in AN count without an increase in abscesses or draining fistulas. Two patients did discontinue their participation in the study, but no serious treatment-emergent adverse events were reported, Incyte said. Opzelura is a cream version of Incyte’s blockbuster Jakafi and scored its original approval in 2021 for atopic dermatitis, adding on an indication for vitiligo the following year. The med is currently the only topical JAK inhibitor on the U.S. market, but Leo Pharma and its contender delgocitinib stand to put pressure on Incyte’s dominance. Recently, the company has been steadily reporting positive phase 3 studies of its JAK inhibitor cream in chronic hand eczema. Elsewhere in Incyte’s JAK inhibitor arsenal is its oral povorcitinib, which just showed significant improvements in itch and disease severity in a phase 2 study in prurigo nodularis. Opzelura is also being tested in prurigo nodularis and is proving to be a rising star for Incyte. The drug brought in $338 million in 2023 sales as “one of the best recent dermatology launches,” the company's North American general manager Barry Flannelly said on the company’s fourth-quarter and full-year earnings conference call.