Kiniksa Pharmaceuticals Announces Development of KPL-387 in Recurrent Pericarditis and Updates Corporate Strategy

Rhea-AI Summary

Kiniksa Pharmaceuticals announced the development of KPL-387 for recurrent pericarditis, with plans to initiate a Phase 2/3 clinical trial in mid-2025. Phase 1 single ascending dose data supports potential monthly dosing with a subcutaneous injection in liquid formulation.

The company is prioritizing cardiovascular indications in its development strategy while discontinuing abiprubart development in Sjögren's Disease and terminating its mavrilimumab license agreement with MedImmune.

Since launching ARCALYST in 2021 for recurrent pericarditis, Kiniksa has generated over $800 million in product revenue and achieved positive annual cash flow. The company plans to further increase ARCALYST's market penetration while developing KPL-387 to expand treatment options.

Additionally, Kiniksa is advancing KPL-1161, another monoclonal antibody targeting IL-1R1, with a target profile of quarterly subcutaneous dosing.

Positive

• KPL-387 Phase 1 data supports potential monthly dosing for recurrent pericarditis
• ARCALYST has generated over $800 million in revenue since 2021 launch
• Company has become cash flow positive on an annual basis
• Phase 2/3 trial for KPL-387 planned for mid-2025
• KPL-1161 advancing toward clinical development with quarterly dosing target

Negative

• Discontinuing abiprubart development in Sjögren's Disease
• Terminating exclusive license agreement for mavrilimumab with MedImmune

Insights

Pharmaceutical Analyst

Kiniksa's strategic pivot to focus on cardiovascular indications represents a significant development for investors, particularly its expansion in the recurrent pericarditis market where the company has already established dominance with ARCALYST.

The $800+ million in ARCALYST revenue since 2021 is substantial relative to Kiniksa's ~$1.4 billion market cap, highlighting how important this franchise is to the company's valuation. ARCALYST has transformed Kiniksa into a cash flow positive operation, providing financial stability to fund pipeline development without dilutive financing - a rare position for a company of this size in the biotech sector.

KPL-387's development in recurrent pericarditis (inflammation of the membrane surrounding the heart) represents a strategic expansion of Kiniksa's cardiovascular portfolio. The potential monthly dosing regimen would offer significant advantages over more frequent administration schedules, improving patient compliance and quality of life. This positions KPL-387 as potentially complementary to ARCALYST rather than cannibalistic - possibly serving different patient segments based on administration preferences or treatment response profiles.

The Phase 2/3 trial initiation in mid-2025 suggests potential approval no earlier than 2027-2028, assuming standard development timelines. This extended horizon means near-term financials will continue to be driven by ARCALYST performance.

The discontinuation of abiprubart for Sjögren's Disease and termination of the mavrilimumab license represent prudent capital allocation decisions. Rather than spreading resources across multiple therapeutic areas, Kiniksa is doubling down on its proven expertise in IL-1 targeted therapies for cardiovascular conditions. This focus should improve R&D efficiency and increase the probability of clinical and commercial success.

KPL-1161's advancement with quarterly dosing potential further reinforces this strategic direction, potentially offering an even more convenient administration schedule for chronic conditions. This creates a compelling portfolio approach to recurrent pericarditis treatment with options for different patient needs.

For investors, this strategic realignment transforms Kiniksa from a diversified, higher-risk biotech into a more focused cardiovascular specialist with proven commercial capabilities and multiple shots on goal within a defined therapeutic area. This focus-driven approach has historically created more shareholder value in the biotech sector than diversified models at companies of Kiniksa's size.

Cardiovascular Disease Specialist

The development of KPL-387 for recurrent pericarditis represents a clinically significant expansion of Kiniksa's cardiovascular inflammation portfolio. This strategic focus on IL-1 pathway inhibition in pericarditis builds upon solid scientific rationale, as both IL-1α and IL-1β are established mediators of the inflammatory response in this condition.

While both KPL-387 and ARCALYST target the IL-1 pathway, their mechanisms differ in ways that could translate to distinct clinical profiles. ARCALYST functions as an IL-1 trap protein that binds circulating cytokines, while KPL-387 directly blocks the IL-1 receptor (IL-1R1). This receptor-level inhibition may potentially offer more complete pathway blockade, particularly at tissue sites where the receptor is expressed.

The monthly subcutaneous dosing potential of KPL-387 represents a substantial improvement over ARCALYST's weekly administration requirement. For patients with this chronic condition, reducing injection frequency from 52 to 12 times annually could significantly improve treatment adherence and quality of life. The liquid formulation further enhances convenience compared to ARCALYST's lyophilized powder requiring reconstitution.

Recurrent pericarditis affects approximately 40,000 patients in the United States, with roughly 5,000-8,000 being refractory to conventional therapies like NSAIDs, colchicine, and corticosteroids. While this represents a relatively small population, the chronic nature of the condition and treatment options have enabled premium pricing, as evidenced by ARCALYST's strong revenue generation.

The planned Phase 2/3 trial design likely mirrors ARCALYST's successful RHAPSODY study, focusing on time-to-recurrence endpoints. Patient recruitment may face challenges given ARCALYST's established position, though the promise of less frequent dosing could drive interest. The mid-2025 trial initiation suggests potential approval in 2028-2029, assuming standard development timelines.

Kiniksa's parallel development of KPL-1161 with quarterly dosing potential reveals a sophisticated product lifecycle management strategy. This creates a compelling treatment continuum for recurrent pericarditis: weekly (ARCALYST), monthly (KPL-387), and potentially quarterly (KPL-1161) options. This approach could allow Kiniksa to maintain market exclusivity well beyond ARCALYST's patent expiration while addressing different patient preferences.

The pipeline rationalization to focus exclusively on cardiovascular inflammation represents sound strategic thinking rather than a concerning retreat. By consolidating resources around their area of demonstrated expertise, Kiniksa increases their probability of clinical and commercial success while potentially accelerating time-to-market for their priority programs.

– Kiniksa plans to initiate a Phase 2/3 clinical trial of KPL-387 in recurrent pericarditis in mid-2025 –

– KPL-387 Phase 1 single ascending dose data support potential monthly dosing –

– Kiniksa continues to focus development on diseases with unmet need, prioritizing cardiovascular indications –

– Kiniksa to discontinue abiprubart development in Sjögren’s Disease –

LONDON, Feb. 25, 2025 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals International, plc (Nasdaq: KNSA) (Kiniksa), a biopharmaceutical company developing and commercializing novel therapies for diseases with unmet need, with a focus on cardiovascular indications, today announced the development program for KPL-387 in recurrent pericarditis and provided an update on its corporate strategy. KPL-387 is an independently developed monoclonal antibody that binds human interleukin-1 receptor 1 (IL-1R1), inhibiting the signaling activity of the cytokines interleukin-1α (IL-1α) and interleukin-1β (IL-1β).

“Through the successful development and commercialization of ARCALYST, Kiniksa has helped thousands of patients suffering from recurrent pericarditis. Since the launch in 2021, we have generated over $800 million in product revenue and have become cash flow positive on an annual basis. We plan to further increase our penetration into the recurrent pericarditis population with ARCALYST,” said Sanj K. Patel, Chairman and Chief Executive Officer of Kiniksa. “We also continue to focus development on novel therapies for diseases with unmet need, prioritizing cardiovascular indications. Today, we are excited to extend our leadership in the recurrent pericarditis market through the development of KPL-387. We believe KPL-387 could expand the treatment options for recurrent pericarditis patients by providing a single monthly subcutaneous injection in a liquid formulation.”

“KPL-387 could provide a meaningful addition to the therapeutic options available to patients suffering from recurrent pericarditis. Data generated from the single ascending dose portion of the ongoing Phase 1 study support our belief that KPL-387 could enable dosing with a single monthly subcutaneous injection in a liquid formulation,” said John F. Paolini, M.D., Ph.D., FACC, Chief Medical Officer of Kiniksa. “We have interacted with the FDA, and we plan to initiate a Phase 2/3 clinical trial of KPL-387 in recurrent pericarditis in mid-2025, with Phase 2 data expected in the second half of 2026.”

Corporate Update

• Kiniksa continues to focus development on diseases with unmet need, prioritizing cardiovascular indications.
• Kiniksa is developing KPL-387, a fully human immunoglobulin G2 (IgG2) monoclonal antibody that binds IL-1R1, inhibiting the signaling of the cytokines IL-1α and IL-1β, in recurrent pericarditis with a target profile of monthly subcutaneous (SC) dosing.
  • Kiniksa is conducting a single ascending dose (SAD) and multiple ascending dose Phase 1 clinical trial of KPL-387 in healthy volunteers.
    • Topline data from the SAD portion of the Phase 1 trial of KPL-387 support potential monthly SC dosing in recurrent pericarditis.
  • Kiniksa has interacted with the U.S. Food and Drug Administration (FDA) and expects to initiate a Phase 2/3 clinical trial of KPL-387 in recurrent pericarditis in mid-2025, with Phase 2 data expected in the second half of 2026.
• Kiniksa is advancing KPL-1161, an Fc-modified IgG2 monoclonal antibody that binds IL-1R1, inhibiting the signaling of the cytokines IL-1α and IL-1β, towards clinical development with a target profile of quarterly SC dosing.
• Kiniksa plans to discontinue the development of abiprubart in Sjögren’s Disease. The company will explore strategic alternatives for the asset.
• Kiniksa has exercised its right to terminate its exclusive license agreement for mavrilimumab with MedImmune.

About Kiniksa
Kiniksa is a biopharmaceutical company dedicated to improving the lives of patients suffering from debilitating diseases by discovering, acquiring, developing, and commercializing novel therapies for diseases with unmet need, with a focus on cardiovascular indications. Kiniksa’s portfolio of assets is based on strong biologic rationale or validated mechanisms and offers the potential for differentiation. For more information, please visit www.kiniksa.com.

About ARCALYST
ARCALYST^® (rilonacept) is a weekly, subcutaneously injected recombinant dimeric fusion protein that blocks interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) signaling. ARCALYST was discovered by Regeneron Pharmaceuticals, Inc. (Regeneron) and is approved by the U.S. Food and Drug Administration (FDA) for the treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and children 12 years and older. ARCALYST is also approved by the FDA for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 years and older, and the maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing 10 kg or more. The FDA granted Orphan Drug Exclusivity to ARCALYST upon its approval for recurrent pericarditis in 2021. The European Commission granted Orphan Drug Designation to ARCALYST for the treatment of idiopathic pericarditis in 2021.

IMPORTANT SAFETY INFORMATION ABOUT ARCALYST

• ARCALYST may affect your immune system and can lower the ability of your immune system to fight infections. Serious infections, including life-threatening infections and death, have happened in patients taking ARCALYST. If you have any signs of an infection, call your doctor right away. Treatment with ARCALYST should be stopped if you get a serious infection. You should not begin treatment with ARCALYST if you have an infection or have infections that keep coming back (chronic infection).
• While taking ARCALYST, do not take other medicines that block interleukin-1, such as Kineret^® (anakinra), or medicines that block tumor necrosis factor, such as Enbrel^® (etanercept), Humira^® (adalimumab), or Remicade^® (infliximab), as this may increase your risk of getting a serious infection.
• Talk with your doctor about your vaccine history. Ask your doctor whether you should receive any vaccines before you begin treatment with ARCALYST.
• Medicines that affect the immune system may increase the risk of getting cancer.
• Stop taking ARCALYST and call your doctor or get emergency care right away if you have any symptoms of an allergic reaction.
• Your doctor will do blood tests to check for changes in your blood cholesterol and triglycerides.
• Common side effects include injection-site reactions (which may include pain, redness, swelling, itching, bruising, lumps, inflammation, skin rash, blisters, warmth, and bleeding at the injection site), upper respiratory tract infections, joint and muscle aches, rash, ear infection, sore throat, and runny nose.
  

For more information about ARCALYST, talk to your doctor and see the Product Information.

About KPL-387
KPL-387 is an independently developed, investigational, fully human IgG2 monoclonal antibody that binds IL-1R1, inhibiting the signaling of the cytokines IL-1α and IL-1β. Kiniksa believes KPL-387 could expand the treatment options for recurrent pericarditis patients by enabling dosing with a single monthly SC injection in a liquid formulation.

About KPL-1161
KPL-1161 is an independently developed, investigational, Fc-modified IgG2 monoclonal antibody that binds IL-1R1, inhibiting the signaling of the cytokines IL-1α and IL-1β, with a target profile of quarterly SC dosing. Kiniksa is currently engaging in IND-enabling development activities for KPL-1161.

About Abiprubart
Abiprubart is an investigational humanized monoclonal antibody that binds to CD40 and is designed to inhibit the CD40-CD154 (CD40 ligand) interaction, a key T-cell co-stimulatory signal critical for B-cell maturation and immunoglobulin class switching and Type 1 immune responses. Kiniksa believes disrupting the CD40-CD154 co-stimulatory interaction is an attractive approach to addressing multiple autoimmune disease pathologies.

Forward-Looking Statements
This press release contains forward-looking statements. In some cases, you can identify forward- looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: our plan to initiate a Phase 2/3 clinical trial of KPL-387 in recurrent pericarditis in mid-2025, with Phase 2 data expected in the second half of 2026; our plan to discontinue the development of abiprubart in Sjögren’s Disease and explore strategic alternatives for the asset; our plan to prioritize development in cardiovascular indications; our plan to further increase our penetration into the recurrent pericarditis market with ARCALYST; our belief that KPL-387 could expand the treatment options for recurrent pericarditis patients by providing a single monthly SC injection in a liquid formulation; our target profile of monthly and quarterly SC dosing for KPL-387 and KPL-1161, respectively; our beliefs about the mechanisms of our assets and potential impact of their approach; and our belief that our portfolio of assets offers the potential for differentiation.

These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including without limitation, the following: delays or difficulty in enrollment of patients in, and activation or continuation of sites for, our clinical trials; delays or difficulty in completing our clinical trials as originally designed; potential for changes between final data and any preliminary, interim, top-line or other data from clinical trials; our inability to replicate results from our earlier clinical trials or studies; impact of additional data from us or other companies, including the potential for our data to produce negative, inconclusive or commercially uncompetitive results; potential undesirable side effects caused by our products and product candidates; our inability to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities; potential for applicable regulatory authorities to not accept our filings, delay or deny approval of any of our product candidates or require additional data or trials to support approval; our reliance on third parties as the sole source of supply of the drug substance and drug product used in our products and product candidates; raw material, important ancillary product and drug substance and/or drug product shortages; our reliance on third parties to conduct research, clinical trials, and/or certain regulatory activities for our product candidates; complications in coordinating requirements, regulations and guidelines of regulatory authorities across jurisdictions for our clinical trials; business development activities and their impact on our financial performance and strategy; changes in our operating plan, business development strategy or funding requirements; and existing or new competition.

These and other important factors discussed in our filings with the U.S. Securities and Exchange Commission, including under the caption “Risk Factors” contained therein, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. Except as required by law, we disclaim any intention or obligation to update or revise any forward-looking statements. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

ARCALYST^® is a registered trademark of Regeneron Pharmaceuticals, Inc.

Every Second Counts!^®

Kiniksa Investor Contact
Jonathan Kirshenbaum
(781) 829-3949
jkirshenbaum@kiniksa.com

Kiniksa Media Contact
Tyler Gagnon
(781) 431-9100
tgagnon@kiniksa.com

FAQ

What is Kiniksa's timeline for KPL-387 clinical trials in recurrent pericarditis?

Kiniksa plans to initiate a Phase 2/3 clinical trial of KPL-387 in recurrent pericarditis in mid-2025, with Phase 2 data expected in the second half of 2026.

How much revenue has ARCALYST generated for KNSA since its launch?

Since launching ARCALYST in 2021, Kiniksa (KNSA) has generated over $800 million in product revenue and has become cash flow positive on an annual basis.

What dosing advantage could KPL-387 offer KNSA patients with recurrent pericarditis?

KPL-387 could offer recurrent pericarditis patients a single monthly subcutaneous injection in a liquid formulation, potentially expanding treatment options beyond current therapies.

Why is KNSA discontinuing abiprubart development?

Kiniksa is discontinuing abiprubart development in Sjögren's Disease as part of its strategic focus on cardiovascular indications. The company will explore strategic alternatives for this asset.

What is the target dosing profile for KNSA's KPL-1161 in development?

KPL-1161, an Fc-modified IgG2 monoclonal antibody targeting IL-1R1, has a target profile of quarterly subcutaneous dosing.

How is Kiniksa Pharmaceuticals (KNSA) refocusing its corporate strategy?

KNSA is focusing development on diseases with unmet need, prioritizing cardiovascular indications while discontinuing certain programs like abiprubart in Sjögren's Disease and terminating its mavrilimumab license.