Kiniksa Pharmaceuticals Announces Development Indication for Abiprubart
Kiniksa Pharmaceuticals, announces plans to initiate Phase 2b trial in Sjogren’s Disease and presents positive data from Phase 2 Cohort 4 in rheumatoid arthritis with abiprubart. The company expects to remain cash flow positive and fully fund abiprubart development through Phase 3.
Positive
Kiniksa Pharmaceuticals plans to start a Phase 2b trial with abiprubart in Sjogren’s Disease in 2H 2024.
Data from Phase 2 Cohort 4 of abiprubart in rheumatoid arthritis validate its biological activity.
Abiprubart development in Sjogren’s Disease is fully funded through Phase 3.
Kiniksa expects to stay cash flow positive annually within its current operating plan.
The initiation of the Phase 2b trial for abiprubart in Sjogren's Disease by Kiniksa Pharmaceuticals is a significant step in the realm of autoimmune disease treatment, particularly for a condition lacking FDA-approved therapies. The design of this trial, being randomized, double-blind and placebo-controlled, is the gold standard for determining the efficacy and safety of new treatments. The primary endpoint using the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) provides a quantifiable measure for assessing the impact of the drug on disease activity.
From a medical research perspective, the reported data from the rheumatoid arthritis trials indicating a statistically significant reduction in Rheumatoid Factor is promising. This reduction is an indicator of biological activity and potential clinical efficacy. However, the difference in the least squares mean change in the Disease Activity Score of 28 Joints Using C-reactive Protein (DAS28-CRP) between the treatment and placebo groups in Cohort 4 did not reach statistical significance, which warrants careful interpretation.
The long-term extension phase of the trial is equally important, as it will provide insights into the sustained efficacy and safety profile of abiprubart. The subcutaneous administration route is also noteworthy, as it could offer convenience and improved patient compliance compared to intravenous options.
Kiniksa Pharmaceuticals' announcement regarding their financial guidance, expecting to remain cash flow positive within the current operating plan, is a reassuring signal to investors. The company's strategic capital allocation, supported by ARCALYST revenue growth, underlines a disciplined approach to managing its financial resources. The full funding for abiprubart's development through Phase 3 is indicative of a robust financial strategy and could reduce the risk of dilutive financing rounds or the need for partnerships that might otherwise be necessary to fund expensive late-stage trials.
For stakeholders, the emphasis on long-term value creation is crucial. The potential market for a successful Sjogren's Disease therapy is significant, given the current lack of approved treatments. If abiprubart proves effective, it could capture a substantial market share and drive revenue growth for Kiniksa. However, investors should remain cautious and monitor upcoming trial results, as clinical success is not guaranteed and can impact the company's financial projections and stock performance.
The landscape for Sjogren's Disease treatment represents an untapped market due to the absence of specific FDA-approved therapies. Kiniksa Pharmaceuticals' progression into a Phase 2b trial for abiprubart could potentially meet a significant unmet medical need. The successful development of abiprubart may not only benefit patients with Sjogren's Disease but could also have implications for other autoimmune diseases, given the cross-activity demonstrated in rheumatoid arthritis.
Considering the competitive environment, Kiniksa's strategic focus on immune-modulating assets positions the company in a niche but growing segment of the autoimmune market. The ability to offer a new therapeutic mechanism of action through the inhibition of the CD40-CD154 interaction could differentiate abiprubart from existing therapies, which mainly focus on TNF-alpha inhibitors and other biological pathways.
It is essential to monitor the results of the upcoming Phase 2b trial, as they will be a critical determinant of abiprubart's market potential. The company's anticipation of initiating the trial in the second half of 2024 suggests a proactive approach to development timelines, but also indicates that market entry, if successful, is still several years away.
04/02/2024 - 07:30 AM
– Abiprubart Phase 2b trial in Sjogren’s Disease planned to initiate in 2H 2024 – – Abiprubart Phase 2 Cohort 4 rheumatoid arthritis data further validate biological activity – – Abiprubart development in Sjogren’s Disease fully funded through Phase 3 – – Company expects to remain cash flow positive on an annual basis within current operating plan –
HAMILTON, Bermuda, April 02, 2024 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (Kiniksa), a commercial-stage biopharmaceutical company with a pipeline of immune-modulating assets designed to target a spectrum of cardiovascular and autoimmune diseases, today announced plans to initiate a Phase 2b trial with abiprubart in Sjogren’s Disease. Additionally, the company announced data from Cohort 4 of the Phase 2 clinical trial of abiprubart in rheumatoid arthritis. Abiprubart is an investigational humanized anti-CD40 monoclonal antibody designed to inhibit CD40-CD154 (CD40 ligand) interaction.
“We believe abiprubart has the potential to provide meaningful benefit to patients suffering from Sjogren’s Disease, a debilitating disorder with no current FDA-approved therapies. Based on the clear biological activity demonstrated by abiprubart, potential for convenient subcutaneous administration, and external proof-of-concept of inhibition of the CD40-CD154 interaction, we plan to initiate a Phase 2b trial of abiprubart in Sjogren’s Disease in the second half of 2024,” said Sanj K. Patel, Chairman and Chief Executive Officer of Kiniksa. “Supported by our robust ARCALYST revenue growth and current cash position, we continue to execute a strategic and disciplined capital allocation approach in areas we believe provide the best opportunity to drive long-term value. Based on our current operating plan, which includes advancement of abiprubart through Phase 3 development in Sjogren’s Disease, we expect to remain cash flow positive on an annual basis.”
Phase 2b Clinical Trial of Abiprubart in Sjogren’s Disease
The placebo-controlled portion of the trial will randomize approximately 201 patients in a 1:1:1 ratio to receive abiprubart 400 mg SC biweekly, 400 mg SC monthly, or placebo over a period of 24 weeks. The primary endpoint will be change from baseline in EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI) versus placebo at Week 24. Subsequently, patients will enter a long-term extension in which all patients will receive active treatment for an additional 24 weeks. The trial is expected to initiate in the second half of 2024.
Abiprubart Phase 2 Rheumatoid Arthritis Data
Following previously reported topline data, Kiniksa today announced final data from the first three cohorts of the clinical trial:
In Cohorts 1 and 2, multiple doses of abiprubart were well-tolerated and enabled the proof-of-concept portion of the study. In the Cohort 3 abiprubart 5 mg/kg SC weekly dose group (n=27), the Least Squares (LS) mean change [95% confidence interval (CI)] from baseline in Disease Activity Score of 28 Joints Using C-reactive Protein (DAS28-CRP) at Week 12 was -2.17 [-2.60, -1.74] points, compared to -1.61 [-2.04, -1.17] points in placebo recipients (n=26), (LS Mean Difference = -0.57, p=0.0470). In the Cohort 3 abiprubart 5 mg/kg SC biweekly dose group (n=25), the LS mean change [95% CI] from baseline in DAS28-CRP at Week 12 was -1.96 [-2.40, -1.52] points, compared to -1.61 [-2.04, -1.17] points in placebo recipients (n=26), (LS Mean Difference = -0.36, p=0.2124). There was a statistically significant reduction of over 40% in Rheumatoid Factor, a clinical marker of disease activity and an autoantibody pharmacodynamic marker of CD40 target engagement, in both Cohort 3 abiprubart dose groups (p<0.0001). Abiprubart was well-tolerated, with no dose-related adverse experiences observed. Today, Kiniksa announced topline data from the fourth cohort of the clinical trial:
In the Cohort 4 abiprubart 400 mg SC monthly dose group (n=31), the LS mean change [95% CI] from baseline in DAS28-CRP at Week 12 was -1.87 [-2.54, -1.21] points, compared to -1.30 [-1.98, -0.62] points in placebo recipients (n=20), (LS Mean Difference = -0.58, p=0.109). There was a statistically significant reduction of approximately 40% in Rheumatoid Factor in the abiprubart group (p=0.0003). As in the first three cohorts, abiprubart was well-tolerated, and no dose-related adverse experiences were observed. Additionally, Kiniksa today announced a post-hoc analysis of data pooled from the Cohort 3 and Cohort 4 abiprubart and placebo groups:
In the pooled abiprubart group (n=83), the LS mean change [95% CI] from baseline in DAS28-CRP at Week 12 was -2.04 [-2.34, -1.74] points, compared to -1.52 [-1.88, -1.16] points in placebo recipients (n=46), (LS Mean Difference = -0.52, nominal p=0.010). “These Phase 2 data demonstrate that abiprubart is a potentially efficacious and well-tolerated therapeutic approach for multiple autoimmune diseases, including Sjogren’s Disease,” said John F. Paolini, MD, PhD, Chief Medical Officer of Kiniksa. “The comparable magnitude of reduction in Rheumatoid Factor observed across weekly, biweekly, and monthly dosing and supportive post-hoc analysis of pooled efficacy data reinforce our confidence that abiprubart is highly active. We look forward to initiating the Phase 2b trial in Sjogren’s Disease in the second half of this year.”
Financial Guidance
About Kiniksa www.kiniksa.com .
About Abiprubart
About the Phase 2 Clinical Trial of Abiprubart in Rheumatoid Arthritis
The multiple ascending-dose PK lead-in portion randomized 8 patients each in a 3:1 ratio to receive abiprubart 2 mg/kg or placebo (Cohort 1) or 5 mg/kg or placebo (Cohort 2), administered subcutaneously biweekly over a period of 12 weeks. The primary objective of this part of the trial was to evaluate PK, safety, and tolerability over 12 weeks. The secondary efficacy endpoint was change from baseline in DAS28-CRP versus placebo.
The first part of the proof-of-concept portion of the trial (Cohort 3) randomized 78 patients in a 1:1:1 ratio to receive abiprubart 5 mg/kg SC weekly, abiprubart 5 mg/kg SC biweekly, or placebo over a period of 12 weeks. The final part of the proof-of-concept portion of the trial (Cohort 4) randomized 51 patients in a 3:2 ratio to receive a fixed 600 mg loading dose on Day 1 followed by 400 mg SC every four weeks or placebo over a period of 12 weeks. The primary efficacy endpoint of the proof-of-concept portion of the trial was change from baseline in DAS28-CRP versus placebo.
Forward-Looking Statements
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When will Kiniksa Pharmaceuticals start the Phase 2b trial with abiprubart in Sjogren’s Disease?
Kiniksa Pharmaceuticals plans to initiate the Phase 2b trial with abiprubart in Sjogren’s Disease in the second half of 2024.
What does the data from Phase 2 Cohort 4 of abiprubart in rheumatoid arthritis show?
The data from Phase 2 Cohort 4 of abiprubart in rheumatoid arthritis validates its biological activity.
How is the abiprubart development in Sjogren’s Disease funded?
The abiprubart development in Sjogren’s Disease is fully funded through Phase 3.
What does Kiniksa expect in terms of cash flow positivity within its current operating plan?
Kiniksa expects to remain cash flow positive on an annual basis within its current operating plan.
What is the ticker symbol for Kiniksa Pharmaceuticals?
The ticker symbol for Kiniksa Pharmaceuticals is KNSA.
