Pharma COVID Roundup: News from Moderna, J&J, Lilly, and AbbVie
The latest on manufacturing and potential treatments for COVID-19 with news from Moderna, J&J, Lilly, AbbVie, Novavax, Daiichi Sankyo, CSL, and AstraZeneca.
Moderna Advances Late-Stage Development of COVID-19 Vaccine
Moderna, a clinical-stage biopharmaceutical company developing messenger RNA (mRNA) therapeutics and vaccines, provided an update of mRNA-1273, the company’s mRNA vaccine candidate against COVID-19.
Moderna has finalized the Phase III study protocol based on feedback from the US Food and Drug Administration (FDA). The randomized, 1:1 placebo-controlled trial is expected to include approximately 30,000 participants enrolled in the US and is expected to be conducted in collaboration with the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The trial’s primary endpoint will be the prevention of symptomatic COVID-19 disease; key secondary endpoints include prevention of severe COVID-19 disease (as defined by the need for hospitalization) and prevention of infection by SARS-CoV-2, the virus that causes COVID-19. The primary efficacy analysis will be an event-driven analysis based on the number of participants with symptomatic COVID-19 disease.
Based on the results of the Phase I study, the 100 μg dose level was chosen as the optimal dose level to maximize the immune response while minimizing adverse reactions. Moderna has completed manufacture of vaccine required to start the Phase III study. The company expects dosing in the Phase III study to begin in July (July 2020).
With the Phase III dose being finalized at 100 μg, Moderna says it remains on track to be able to deliver approximately 500 million doses per year, and possibly up to 1 billion doses per year, beginning in 2021 from the company’s internal US manufacturing site and strategic collaboration with Lonza.
Funding from the Biomedical Advanced Research and Development Authority, a division of the Office of the Assistant Secretary for Preparedness and Response within the US Department of Health and Human Services, supported the planning for these studies and the company will also support the late-stage clinical development programs, as well as the scale-up of mRNA-1273 manufacturing both at the company’s facilities and that of its strategic collaborator, Lonza.
J&J To Begin Phase I/IIa Trial of COVID-19 Vaccine Candidate in July
Johnson & Johnson’s Janssen has accelerated the initiation of a Phase I/IIa first-in-human clinical trial of its investigational SARS-CoV-2 vaccine, Ad26.COV2-S, recombinant, originally set to begin in September (September 2020), will now begin in the second half of July (July 2020).
The randomized, double-blind, placebo-controlled Phase I/IIa study will evaluate the safety, reactogenicity, and immunogenicity of the investigational SARS-CoV-2 vaccine, Ad26.COV2-S, recombinant in 1,045 healthy adults aged 18 to 55 years, as well as adults aged 65 years and older. The study will take place in the US and Belgium.
J&J says it is in discussions with the National Institutes of Allergy and Infectious Diseases with the objective to start the Phase III clinical trial of the SARS-CoV-2 vaccine, Ad26.COV2-S, recombinant, ahead of its original schedule, pending outcome of Phase I studies and approval from regulators.
As the company progresses the clinical development of its investigational SARS-CoV-2 vaccine, Ad26.COV2-S, recombinant, it continues to increase manufacturing capacity and is in active discussions with global partners to ensure worldwide access. J&J says it is committed to the goal of supplying more than one billion doses globally through the course of 2021, provided the vaccine is effective.
J&J’s efforts to expedite development and production of a SARS-CoV-2 vaccine are enhanced by a collaboration between Janssen and the Biomedical Advanced Research and Development Authority, part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health & Human Services.
Source: Johnson & Johnson
Lilly, Junshi Start Phase I Study for Potential COVID-19 Antibody Treatment
Eli Lilly and Company reports that its partner, Junshi Biosciences, a Shanghai-based biopharmaceutical company, has dosed the first healthy volunteer in a Phase I clinical study in China of a potential neutralizing antibody treatment, JS016, designed to address COVID-19.
Should Phase I results show the antibody can be safely administered, Junshi Biosciences says it intends to move to the next phase of testing to study the antibody’s ability to prevent and treat COVID-19.
The investigational medicine, JS016, is being co-developed by Junshi Biosciences and Lilly, with Junshi Biosciences leading development in Greater China. Lilly has exclusive rights in the rest of the world and will begin dosing patients in a complementary Phase I study in the US in the coming days (as reported on June 8, 2020). Both Phase I studies aim to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of JS016 in healthy participants who have not been diagnosed with COVID-19. This is Lilly’s second neutralizing antibody to start clinical trials, following LY-CoV555, which recently entered Phase I and is currently being tested in hospitalized COVID-19 patients.
Lilly says it is planning a clinical development program that includes a portfolio of monotherapy and combination antibody regimens (often referred to as antibody “cocktails”) in order to understand which provides the best efficacy and tolerability in patients. These cocktails will include JS016, LY-CoV555, as well as additional antibodies currently in preclinical development. JS016 and LY-CoV555 bind different epitopes on the spike protein and expand the diversity of options for achieving efficacy and avoiding resistance.
Novavax Awarded $60 M by US Gov’t for COVID-19 Vaccine
Novavax, a Gaithersburg, Maryland-based clinical-stage vaccine company, has been awarded a contract worth up to $60 million by the US Department of Defense (DoD) for the manufacturing of NVX‑CoV2373, Novavax’s COVID-19 vaccine candidate. NVX‑CoV2373 consists of a stable, prefusion protein antigen made using its proprietary nanoparticle technology and includes Novavax’s proprietary saponin-based adjuvant, Matrix‑M.
The Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, through funding provided by the Defense Health Program, has agreed to fund up to $60 million to support Novavax in its production of several components of the vaccine that will be manufactured in the US. The agreement includes a 2020 delivery of 10 million doses of NVX‑CoV2373 for DoD that could be used in Phase II/III clinical trials or under an emergency use authorization if approved by the US Food and Drug Administration.
As part of the contract, Novavax will work with a US-based biologics CDMO to manufacture the antigen component of NVX-CoV2373 for at least 10 million doses of vaccine. Novavax will also collaborate with US-based CDMOs to scale up production and manufacture of the Matrix-M adjuvant component of the vaccine.
AbbVie Enters Pact to Develop COVID-19 Antibody Therapy
AbbVie, Harbour BioMed, a Cambridge, Massachusetts-based clinical-stage biopharmaceutical company developing therapeutics for immuno-oncology and inflammatory diseases, Utrecht University, based in the Netherlands, and the Erasmus Medical Center, based in Rotterham, Netherlands and affiliated with Erasmus University, have entered into a collaboration to develop a novel antibody therapeutic to prevent and treat COVID-19.
The focus of the collaboration is on advancing the fully human, neutralizing antibody, 47D11, discovered by Utrecht University, Erasmus Medical Center and Harbour BioMed and recently reported in Nature Communications. This antibody targets the conserved domain of the spike protein of SARS-CoV-2, the virus that causes COVID-19.
Under the collaboration, AbbVie will support Utrecht University, Erasmus Medical Center and Harbour BioMed through preclinical activities while simultaneously undertaking preparations for later-stage preclinical and clinical development work. AbbVie will receive an option to exclusively license the antibody from the three parties for therapeutic clinical development and commercialization.
Daiichi Sankyo To Collaborate on R&D of COVID-19 Treatment
Daiichi Sankyo, the University of Tokyo, Riken, a Tokyo-based scientific research institute, and Nichi-Iko Pharmaceutical, a Tokyo-headquartered generic-drug company, have reached a basic agreement on collaborative R&D on a nafamostat inhalation formulation for the treatment of COVID-19.
Nafamostat is an injectable that has been prescribed in Japan as a treatment for acute pancreatitis and disseminated intravascular coagulation. In the first stage of infection of SARS-CoV-2, the virus that causes COVID-19, the outer envelope of the virus fuses with the host-cell surface membrane. Prof. Junichiro Inoue, Institute of Medical Science at the University of Tokyo, and others discovered that by preventing this fusion, nafamostat could efficiently inhibit the viral-entry process
Riken has established the program for drug discovery and medical technology platforms in order to optimize the medical seeds generated from basic research at Riken and at universities for use in the drug-discovery process at pharmaceutical companies, and in clinical practice, as a bridge to companies and medical institutions. In this case, Riken says it will also support this collaborative R&D using its multidisciplinary advanced technologies.
Nichi-Iko, the marketing authorization holder of Futhan (nafamostat mesilate), will provide data collected on the product as well as supply the active pharmaceutical ingredient for this collaborative R&D.
Daiichi Sankyo will carry out R&D on the nafamostat inhalation formulation using technology gained in the development of its anti-influenza virus agent, Inavir (laninamivir). Non-clinical studies are scheduled to begin in July (July 2020) and after consultation with authorities with the aim of proceeding to clinical studies by March 2021.
CSL, CEPI, University of Queensland Enter Pact for COVID-19 Vaccine Candidate
CSL, the Coalition for Epidemic Preparedness Innovations (CEPI), a public–private coalition that seeks to derail epidemics by speeding up the development of vaccines, and The University of Queensland (UQ) in Brisbane, Australia, have entered into a partnering agreement to accelerate the development, manufacture and distribution of a COVID-19 vaccine candidate developed by researchers at UQ.
CEPI and CSL will fund the development and manufacture of UQ’s “molecular clamp”-enabled vaccine for COVID-19. Funding contributions will be used to provide support for the pending Phase I safety study being led by UQ followed by subsequent late-stage clinical trials, and industrial-scale manufacturing to allow the production of potentially millions of doses a year, should the product be approved.
The initial phase of large-scale production of the UQ COVID-19 vaccine is planned to take place at CSL’s biotech manufacturing facilities in Melbourne, Australia. CSL anticipates that production technology can be scaled to produce up to one hundred million doses toward the end of 2021. CSL says it will subcontract other global manufacturers to increase the number of doses that can be produced and broaden the geographical distribution of vaccine production. Should clinical trials be successful, a vaccine could be available for distribution in 2021.
CEPI entered into a framework agreement with UQ in January 2019 to provide up to $10.6 million to develop a rapid response “molecular clamp” vaccine platform, a technology patented by UniQuest, UQ’s technology-transfer company that enables rapid vaccine design and production against outbreak viral pathogens. In January 2020, CEPI expanded its partnership with UQ to use its rapid response molecular clamp vaccine platform to produce a vaccine candidate for COVID-19. UQ is now aiming to take the vaccine candidate into a Phase I clinical trial in July (July 2020).
Under the agreement, the allocation of doses between CEPI and CSL is linked to their relative contribution to overall project costs. Should the UQ COVID-19 vaccine be successful, 100% of CEPI’s vaccine allocation will be distributed through the COVID-19 Vaccine Global Access Facility, an instrument of the vaccines pillar of the Access to COVID-19 Tools (ACT) Accelerator, a collaborative taskforce to promote the development, production and equitable distribution of vaccines, diagnostics and therapeutics for COVID-19, within which CEPI works in partnership with Gavi, a global public health partnership, and the World Health Organization. CSL’s allocation will be used to support its biosecurity commitment to the Australian community as well as other key groups, such as its regional neighbors. CSL has granted CEPI a first right of refusal to any surplus doses, to be distributed through the COVID-19 Vaccine Global Access Facility.
AstraZeneca’s Calquence Shows Clinical Improvement in COVID-19 Patients
Results published in Science Immunology showed that AstraZeneca’s Calquence (acalabrutinib), a Bruton’s tyrosine kinase (BTK) inhibitor, reduced markers of inflammation and improved clinical outcomes of patients with severe COVID-19 disease.
The peer-reviewed case series of 19 hospitalized patients with COVID-19 disease and severe hypoxia and/or inflammation is a collaboration from investigators across the US. The publication describes the effects of Calquence administration in patients with severe respiratory illness caused by the SARS-CoV-2 virus. A virus-induced hyperimmune response or “cytokine storm” is hypothesized to be a major pathogenic mechanism of respiratory illness in these patients, and evidence suggests that dysregulated BTK-dependent lung macrophage signaling mediates this cytokine storm and plays a role in COVID-19 pneumonia.
Calquence is a selective BTK inhibitor currently approved in the US for the treatment of certain hematological malignancies. Calquence is not currently approved in any country to treat patients with illnesses related to SARS-CoV-2.