The primary endpoint of HiSCR75 at week 16 did not meet statistical significance in the Non-Responder Imputation (NRI) primary analysis.
HiSCR75 did meet statistical significance at week 16 in a Last Observation Carried Forward sensitivity analysis.
HiSCR response rates of izokibep 160mg weekly (QW) were consistent with Part A open label results, demonstrating early onset of HiSCR100 at week 4, increasing through week 12 to 38% of patients in the Independently Conducted Pre-Planned Interim Analysis.
Response was dose ordered, and safety was consistent with prior izokibep experience and not dose-limiting.
Izokibep appears to be demonstrating consistent early and high orders of response without safety or tolerability limitation.
Conference call and webcast to be held at 5:30 p.m. ET today.
LOS ANGELES, Sept. 11, 2023 (GLOBE NEWSWIRE) -- ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today announced top-line results from Part B of a Phase 2b/3 trial evaluating izokibep for the treatment of moderate-to-severe Hidradenitis Suppurativa (HS). The primary endpoint of HiSCR75 at week 16 did not meet statistical significance. However, response rates for izokibep showed early HiSCR100 responses, a clear dose-effect supported by both pharmacokinetic exposures and HiSCR responses favoring 160mg weekly dosing, and no evidence of safety or tolerability limitation.
“First, I would like to thank the patients and clinicians in this study, without whom we would not be able to continue to learn about how best to treat this debilitating disease. Although the overall study did not meet statistical significance, izokibep appears to be demonstrating consistent early and high orders of response for patients suffering from hidradenitis suppurativa without safety or tolerability limitation,” said Shao-Lee Lin, MD, PhD, founder and CEO of ACELYRIN. “The consistent and early achievement of HiSCR100, along with our prior izokibep experience in Psoriatic Arthritis, continues to demonstrate the potential of izokibep for resolution of disease, especially in difficult to treat tissues. These results further support our ongoing evaluations of 160 mg QW dosing in HS, as well as for additional indications, including uveitis and PsA, the largest potential indication for izokibep.”
The randomized double-blind, placebo-controlled, multi-center trial evaluated the safety and efficacy of izokibep dosed 160 mg weekly (QW) and every two weeks (Q2W), versus placebo, in 175 patients with moderate-to-severe HS (Hurley Stage II and III). The trial was conducted at 50 sites globally and assessed various efficacy endpoints, including the primary endpoint of HiSCR75 (Hidradenitis Suppurativa Clinical Response) at 16 weeks utilizing a non-responder imputation (NRI) analysis method.
In the primary NRI analysis of Part B, statistical significance was impacted by patients with HiSCR75-100 discontinuing as early as week 4 unrelated to adverse events. In addition, there was a marked increase in placebo rates during the course of the study. Applying a Last Observation Carried Forward (LOCF) sensitivity analysis of the full dataset highlighted the impact of responder discontinuations on the primary analysis and showed statistical significance of HiSCR75 at week 16.
| Endpoint | Part B NRI Izokibep 160 mg QW (n=57) | Part B NRI Izokibep 160 mg Q2W (n=59) | Part B NRI Placebo (n=59) |
| HiSCR75 p-value | 39% 0.3278 | 34% 0.5997 | 29% |
| HiSCR100 p-value | 26% 0.0595 | 22% 0.1408 | 12% |
| Endpoint | Part B LOCF Izokibep 160 mg QW (n=54) | Part B LOCF Izokibep 160 mg Q2W (n=57) | Part B LOCF Placebo (n=57) |
| HiSCR75 p-value | 51% 0.0423 | 36% 0.7451 | 32% |
| HiSCR100 p-value | 30% 0.0751 | 22% 0.3558 | 15% |
An independently conducted pre-planned interim analysis, to which the company remained blinded until the time of this primary analysis, occurred prior to a rise in placebo rates observed later in the trial. This dataset provides an opportunity to view the performance of izokibep prior to this increase. The table below shows the consistency of Part A open label results relative to the Part B placebo-controlled interim analysis, which was pre-specified to be an as observed analysis at week 12.
| Endpoint | Part A Izokibep 160 mg QW (n=21) | Part B Interim Izokibep 160 mg QW (n=21) | Part B Interim Izokibep 160 mg Q2W (n=27) | Part B Interim Placebo (n=23) |
| HiSCR75 p-value | 57% | 52% 0.018 | 30% 0.435 | 17% |
| HiSCR100 p-value | 33% | 38% 0.009 | 11% 0.518 | 4% |
Also, given the number of responders who discontinued in the QW arm – the majority unrelated to an adverse event – a modified-NRI (mNRI) approach showed a high level of statistical significance and highlighted the impact of discontinuations on magnitude and significance of response. This analysis demonstrates the performance of izokibep at this juncture in the study – in isolation from the placebo rate increases observed later in the trial – and provides an exploratory approach to analyzing responder discontinuations.
| Endpoint | Part B Interim mNRI Izokibep 160 mg QW (n=31) | Part B Interim mNRI Izokibep 160 mg Q2W (n=28) | Part B Interim mNRI Placebo (n=27) |
| HiSCR75 p-value | 45% 0.0062 | 25% | 15% |
| HiSCR100 p-value | 29% 0.0054 | 11% | 4% |
The safety profile for izokibep was consistent with prior studies and the anti-IL-17A class. There were no events of candida in the high dose 160mg QW arm and there were two discontinuations across the trial due to injection site reactions (3.5%).
The Company is in a strong financial position and expects its existing cash to fund operations through key value-driving milestones across our portfolio. Cash, cash equivalents and short-term marketable securities totaled $823.0 million at June 30, 2023. Top-line data for the ongoing placebo-controlled Phase 2b/3 trial in PsA and proof-of-concept data for lonigutamab in thyroid eye disease are expected by end of Q1 2024
Conference Call Information
ACELYRIN will host a conference call and webcast today, September 11, 2023, at 5:30 p.m. ET to review these trial results. A live webcast of the conference call can be accessed in the “Investors & Media” section of ACELYRIN’s website at www.acelyrin.com. A recording of the webcast will be available approximately two hours after the event, and will be archived on the Company’s website for approximately 30 days.
About Izokibep
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).
About ACELYRIN
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.
Forward Looking Statements
This press release contains forward-looking statements including, but not limited to, statements related to ACELYRIN’s ability to accelerate the development and delivery of transformative medicines; anticipated development activities including establishment of proof of concept and/or the availability of clinical data; the therapeutic potential of ACELYRIN’s product candidates including its ability to offer clinically meaningful, differentiated benefits for patients that may include resolution of key manifestations of disease; and other statements that are not historical fact. These forward-looking statements are based on ACELYRIN’s current plans, objectives and projections, and are inherently subject to risks and uncertainties that may cause ACELYRIN’s actual results to materially differ from those anticipated in such forward-looking statements. Such risks and uncertainties include, without limitation, those associated with the successful completion of development and regulatory activities with respect to ACELYRIN’s product candidates; maintaining and defending intellectual property protection; delays or failures to secure adequate supply of its product candidates; legal proceedings, government investigations or other actions; macroeconomic conditions; market volatility; and other risks and uncertainties affecting ACELYRIN including those described from time to time under the caption “Risk Factors” and elsewhere in ACELYRIN’s current and future reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2023. Forward-looking statements contained in this press release are made as of this date, and ACELYRIN undertakes no duty to update such information except as required under applicable law.
ACELYRIN, INC.
Tyler Marciniak
Vice President of Investor Relations,
Communications and Corporate Operations
investors@acelyrin.com
media@acelyrin.com
