Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a biopharmaceutical company with a portfolio of assets designed to modulate immunological pathways across a spectrum of diseases, today outlined its next steps for the development of mavrilimumab, an investigational fully-human monoclonal antibody that blocks activity of granulocyte macrophage colony stimulating factor (GM-CSF) by binding specifically to the alpha subunit of the GM-CSF receptor. This investigational therapy shows promise targeting COVID-19.
“Recent favorable interactions with the FDA, based upon the clinical data generated with mavrilimumab in COVID-19-related ARDS, giant cell arteritis, and rheumatoid arthritis, underscore the broad utility of mavrilimumab and define a regulatory pathway for Phase 3 clinical development for each indication,” said Sanj K. Patel, Chief Executive Officer and Chairman of the Board of Kiniksa. “We believe the ongoing Phase 3 study of mavrilimumab in COVID-19-related ARDS represents the fastest path to potential registration for the asset, and there remains a significant unmet need in these patients. Enrollment in our Phase 3 clinical trial is ongoing, and we expect data in the first quarter of 2022.”
Mavrilimumab Development and Capital Allocation
Interactions between Kiniksa and the U.S. Food and Drug Administration (FDA) on mavrilimumab in COVID-19–related acute respiratory distress syndrome (ARDS), giant cell arteritis (GCA), and rheumatoid arthritis (RA) resulted in a defined path for Phase 3 clinical development for each indication.
Kiniksa believes development of mavrilimumab in COVID-19-related ARDS represents the fastest path to potential registration.
Based upon data from the Phase 2 portion of the Phase 2/3 clinical trial of mavrilimumab in non-mechanically ventilated patients with COVID-19-related ARDS and discussions with the FDA, Kiniksa has adjusted the final sample size to appropriately power the Phase 3 portion of the clinical trial. The Phase 3 clinical trial will enroll a total of approximately 600 non-mechanically ventilated patients. The primary efficacy endpoint remains as the proportion of patients alive and free of mechanical ventilation at Day 29.
The Phase 3 portion of the clinical trial has already enrolled over 400 patients. Kiniksa expects data from the Phase 3 portion of the clinical trial in the first quarter of 2022.
Kiniksa is engaged with the FDA and other government agencies on pathways to accelerate access to mavrilimumab as a potential therapeutic option for COVID-19-related ARDS.
Kiniksa completed an end-of-Phase 2 meeting for GCA with the FDA.
Kiniksa received guidance that a single, well-controlled pivotal Phase 3 clinical trial in approximately 450 patients could be sufficient for registration. The FDA agreed with the proposed 150 mg and 100 mg subcutaneous (SC) bi-weekly dose levels versus placebo on top of a steroid taper and agreed with a 52-week exposure duration to support chronic use.
Kiniksa completed a pre-IND meeting for RA with the FDA.
Kiniksa received guidance that two well-controlled Phase 3 trials in 1,000-1,500 patients with at least one-year of exposure to mavrilimumab could be sufficient for registration in a broad RA population, such as patients with inadequate response to methotrexate and/or methotrexate naïve patients. The FDA agreed with the proposed 150 mg and 100 mg SC bi-weekly dose levels versus placebo.
Mavrilimumab was dosed at 150 mg and 100 mg SC bi-weekly in over 550 RA patients in Phase 2b clinical studies in Europe which achieved prospectively-defined primary endpoints of efficacy and safety.
Kiniksa intends to provide additional updates on the development of mavrilimumab following data from the Phase 3 clinical trial in COVID-19-related ARDS.
Kiniksa’s resources are currently focused on the commercial launch of ARCALYST® (rilonacept) in recurrent pericarditis, the Phase 3 clinical trial of mavrilimumab in COVID-19-related ARDS, the Phase 2b clinical trial of vixarelimab in prurigo nodularis, and the planned Phase 2 clinical trial of KPL-404 in RA. The company continues to expect that its approximately $264.0 million of cash, cash equivalents and short-term investments will fund its current operating plan into 20231.
About Mavrilimumab in COVID-19-related ARDS
Kiniksa believes there remains an urgent unmet need in patients who are hospitalized with COVID-19-related ARDS. Historically, the annual number of pneumonia-associated ARDS cases in the U.S. has averaged over 300,000. In the past year, that number has spiked to more than 1,000,000 due to COVID-19. Over time, the company expects the incidence may revert to historical averages with occasional spikes.
COVID-19-related ARDS patients transition from an early phase of the disease characterized by high viral replication and load to a subsequent phase of aberrant inflammatory response that causes tissue damage and thrombosis, ARDS, and death. Uncontrolled viral replication increases the likelihood of variants that allow the virus to evade the protective effects of vaccines and virus-neutralizing cocktails; however, Kiniksa believes the way mavrilimumab blocks the body’s counterproductive inflammatory reaction is agnostic to the coronavirus sequence. As such, Kiniksa believes mavrilimumab has the potential to remain effective despite the risk from emerging COVID-19 variants.
Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s portfolio of assets, ARCALYST, mavrilimumab, vixarelimab and KPL-404, are based on strong biologic rationale or validated mechanisms, target underserved conditions and offer the potential for differentiation. These assets are designed to modulate immunological pathways across a spectrum of diseases. For more information, please visit www.kiniksa.com.
ARCALYST is a weekly, subcutaneously-injected recombinant dimeric fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. ARCALYST was discovered by Regeneron and is approved by the FDA for recurrent pericarditis, cryopyrin-associated periodic syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome, and deficiency of IL-1 receptor antagonist (DIRA). The FDA granted Breakthrough Therapy designation to ARCALYST for the treatment of recurrent pericarditis in 2019 and Orphan Drug designation to ARCALYST for the treatment of pericarditis in 2020.
Mavrilimumab is an investigational fully-human monoclonal antibody that blocks activity of GM-CSF by specifically binding to the alpha subunit of the GM-CSF receptor. Mavrilimumab was dosed in over 550 patients with RA through Phase 2b clinical studies in Europe and achieved prospectively-defined primary endpoints of efficacy and safety. Kiniksa is evaluating mavrilimumab in GCA, and the Phase 2 clinical trial achieved both the primary and secondary efficacy endpoints with statistical significance. Kiniksa continues to evaluate mavrilimumab in COVID-19-related ARDS. The FDA granted Orphan Drug designation to mavrilimumab for the treatment of GCA in 2020.
Vixarelimab is an investigational fully-human monoclonal antibody that targets oncostatin M receptor beta (OSMRβ), which mediates signaling of interleukin-31 (IL-31) and oncostatin M (OSM), two key cytokines implicated in pruritus, inflammation and fibrosis. Kiniksa believes vixarelimab to be the only monoclonal antibody in development that targets both pathways simultaneously. Kiniksa’s lead indication for vixarelimab is prurigo nodularis, a chronic inflammatory skin condition characterized by severely pruritic skin nodules. The FDA granted Breakthrough Therapy designation to vixarelimab for the treatment of pruritus associated with prurigo nodularis in 2020.
KPL-404 is an investigational humanized monoclonal antibody that is designed to inhibit 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 interaction is an attractive approach for multiple autoimmune disease pathologies. Kiniksa owns or controls the intellectual property related to KPL-404.