Akari Therapeutics Announces International Clinical Development Program of Nomacopan for the Potential Treatment of COVID-19 Pneumonia
- Clinical studies both underway and planned for patients with COVID-19 pneumonia in the
U.S., U.K., and Brazil
- Proposed multi-center
U.S.randomized clinical program in regulatory submission following the treatment of patients via expanded access programs
Brazil, patient recruitment completed for proof of principle (POP) clinical study; potential progression into follow-on randomized study expected early Q4 2020
- Nomacopan selected by AGILE COVID-19 clinical trial initiative in the
- Data from approximately 50 U.K. patients expected early Q4 2020 from an observational study focused on identifying potential therapeutic biomarkers for optimizing use of nomacopan for COVID-19 pneumonia patients
- Proposed multi-center
- Nomacopan has been shown in clinical trials to inhibit both complement C5 activation and leukotriene B4 (LTB4), and has significant potential to simultaneously inhibit both microthrombi as well as block multiple cytokines (the cytokine storm) which together drive COVID-19 pneumonia and associated organ damage.
- Ongoing clinical readouts expected throughout remainder of 2020
- Akari hosting webcast today at
8:30 am EDT( 1:30 pm BST).
Scientific rationale for potential use of nomacopan in COVID-19 pneumonia
Nomacopan’s dual complement (C5) and leukotriene (LTB4) inhibition blocks several key inflammatory pathways that drive COVID-19 pneumonia.
Terminal complement activation by formation of C5a and the membrane attack complex (C5b9) is associated with direct vascular damage, microthrombi and long-term damage to the lung and other organs in COVID-19 patients1. A causative role for complement activation has been shown in other inflammatory diseases with shared pathophysiological components, such as hematopoietic stem cell transplant-related thrombotic microangiopathy (TMA-HSCT)2 in which Akari has an open Phase III Investigational New Drug (IND) application.
Neutrophil accumulation in the lungs is another key feature of COVID-19 pneumonia, resulting in ‘cytokine storm syndrome’ and associated epithelial damage in lung and other organs. Leukotriene (LTB4) is one of the most potent known chemo attractants of neutrophils and other neutrophil chemo-attractants appear to rely on LTB4 synthesis for recruitment of neutrophils from distal sites. Leukotriene inhibitors are approved for treatment of asthma and are being tested in COVID-19 pneumonia3 due to their ability to block multiple cytokines. Cytokines and chemokines inhibited by nomacopan4 include GM-CSF, IL1 alpha, IL1beta, IL2, IL-6, IL17, TNF, RANTES, MCP1, MIP1alpha andMIP1beta all of which have been reported to be elevated in COVID-19 pneumonia patients5.
The potential additive benefits of both C5 and LTB4 inhibition by nomacopan have previously been demonstrated in preclinical models of viral induced acute respiratory distress syndrome (ARDS) with reduced inflammation and mortality6. Moreover, the combined inhibition of both C5 and LTB4 demonstrated by nomacopan was superior to inhibition by either C5 or LTB4 alone in a mouse model of acute lung inflammation, highlighting the additive effect of inhibiting both these innate immune pathways7.
Akari believes that this inhibition of multiple inflammatory pathways distinguishes nomacopan from other potential therapies focused on a single mechanism of action. In addition to nomacopan’s fast onset of action, the rapid normalization of complement and LTB4 levels at the end of treatment has the potential to avoid the risks of longer-term immunosuppression typical of monoclonal antibodies.
Staged clinical development plan with nomacopan for the treatment of COVID-19 pneumonia
Akari’s strategy for advancing clinical development of nomacopan as a potential COVID-19 pneumonia treatment includes: (1) identifying biomarkers to optimize patient selection; (2) completing initial proof of principle studies in hospitalised COVID-19 patients; (3) conducting integrated randomized clinical trials in the
An observational study relating to biomarkers that may identify COVID-19 patients who are particularly suitable for nomacopan treatment is ongoing in the
Initial POP treatment in patients with COVID-19 pneumonia via expanded access programs (EAPs) are ongoing in the US. In
These COVID-19 programs build on the existing Akari clinical experience in the use of nomacopan, underpinned by 35 cumulative patient-years of nomacopan safety data with no reported drug related SAEs, and clinical response across a range of inflammatory conditions in Phase II and Phase III development.
Planned randomized clinical studies
Akari intends to conduct multiple randomized controlled studies in the
Subject to additional comments from regulators, the trial protocols for the planned randomized clinical trials would provide for patients to be randomized 2:1 nomacopan plus standard of care (SoC) or SoC alone, with an initial target of around 60 patients in each of the individual study settings. Patients would be on supportive oxygen (not intubated) and be recruited following admission to hospital. The primary endpoint is time to normalization of oxygen, while the secondary endpoint will include need for intubation and mortality. Patients will receive a daily subcutaneous dose of nomacopan for up to 14 days, with study monitoring and completion after two months. The SoC arm for the trials incorporates the latest treatments where available, including dexamethasone and remdesivir, both of which have a different mode of action to nomacopan and as such, nomacopan has the potential to add additional efficacy to either or both of these treatments. In examining the efficacy of nomacopan Akari expects to consider the totality of the data across these studies using the same endpoints.
- Ramlall, et al., Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection, 2020
- Merrill, et al., Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications, 2020
- Funk, et al., A Novel Strategy to Mitigate the Hyperinflammatory Response to COVID-19 by Targeting Leukotrienes, 2020
- Huber-Lang, et al., Double Blockade of CD14 and Complement C5 Abolishes the Cytokine Storm and Improves Morbidity and Survival in Polymicrobial Sepsis in Mice, 2014
- Mehta P, et al., COVID-19: consider cytokine storm syndromes and immunosuppression, 2020
- Garcia, et al., Complement C5 Activation during Influenza A Infection in Mice Contributes to Neutrophil Recruitment and Lung Injury, 2013
- Roversi, et al., Bifunctional Lipocalin Ameliorates Murine Immune complex-induced Acute Lung Injury, 2013
Conference call and webcast
Akari will host a conference call and webcast today,
About Akari Therapeutics
Akari is a biopharmaceutical company focused on developing inhibitors of acute and chronic inflammation, specifically for the treatment of rare and orphan diseases, in particular those where the complement (C5) or leukotriene (LTB4) systems, or both complement and leukotrienes together, play a primary role in disease progression. Akari's lead drug candidate, nomacopan (formerly known as Coversin), is a C5 complement inhibitor that also independently and specifically inhibits leukotriene B4 (LTB4) activity.
Cautionary Note Regarding Forward-Looking Statements
Certain statements in this press release constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. You should not place undue reliance upon the Company’s forward looking statements. Except as required by law, the Company undertakes no obligation to revise or update any forward-looking statements in order to reflect any event or circumstance that may arise after the date of this press release. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to
+1 (443) 213-0505
Sukaina Virji / Lizzie Seeley
+44 (0)20 3709 5700
Source: Akari Therapeutics Plc