Pharma COVID Roundup: News from AstraZeneca, Pfizer, Lilly, Gilead, GSKBy
The latest on manufacturing and potential treatments for COVID-19 with news from AstraZeneca, Pfizer, Eli Lilly and Company, Gilead Sciences, GSK, Eisai, and others.
EMA Begins Rolling Review of AstraZeneca’s COVID-19 Vaccine
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has started a rolling review of AstraZeneca’s COVID-19 vaccine candidate, AZD1222.
A rolling review is one of the regulatory tools that the EMA uses to speed up the assessment of a promising medicine or vaccine during a public health emergency. Normally, all data on a medicine’s effectiveness, safety and quality and all required documents must be submitted at the start of the evaluation in a formal application for marketing authorization. In the case of a rolling review, the CHMP reviews data as they become available from ongoing studies before deciding that sufficient data are available and that a formal application should be submitted by the company.
CHMP has started evaluating the first batch of data on the vaccine, which come from laboratory studies (non-clinical data). The agency says this does not mean that a conclusion can be reached yet on the vaccine’s safety and effectiveness as much of the evidence is still to be submitted.
AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech, and licensed to AstraZeneca. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.
The CHMP’s decision to start the rolling review of the vaccine is based on preliminary results from non-clinical and early clinical studies suggesting that the vaccine triggers the production of antibodies and T cells (cells of the immune system, the body’s natural defenses) that target the virus. The rolling review will continue until enough evidence is available to support a formal marketing authorization application.
The EMA says it will complete its assessment according to its usual standards for quality, safety and effectiveness. While the overall review timeline cannot be forecast yet, the process should be shorter than a regular evaluation due to the time gained during the rolling review. The rolling review process has been used previously in the assessment of Gilead Sciences’ COVID-19 treatment, Veklury (remdesivir).
In a separate development, AstraZeneca reports that the Phase I/II clinical trial for its COVID-19 vaccine, AZD1222, has resumed in Japan after discussions with the Japanese Pharmaceuticals and Medical Devices Agency.
The company had paused global clinical trials of the vaccine last month (September 2020) to allow an independent committee to review the safety data of a single event of an unexplained illness that occurred in a Phase III trial in the UK. Since then, in addition to regulators in Japan, regulators in the UK, Brazil, South Africa, and India have deemed the trials are safe to resume.
AstraZeneca says it continues to work with the US Food and Drug Administration to facilitate review of the information needed to make a decision regarding resumption of the US trial.
Pfizer, BioNTech Initiate Rolling Submission to EMA for COVID Vaccine
Pfizer and BioNTech, a Mainz, Germany-based immunotherapy company, have initiated a rolling submission to the European Medicines Agency (EMA) for BNT162b2, the lead candidate from the companies’ vaccine development program against COVID-19.
The EMA’s decision to start a rolling review follows preliminary results from preclinical and early clinical studies in adults, which suggest that BNT162b2 triggers the production of neutralizing antibodies and TH-1 dominant CD4+ and CD8+ T cells that target SARS-CoV-2, the virus that causes COVID-19. BioNTech and Pfizer say they plan to work with the EMA’s Committee for Medicinal Products for Human Use (CHMP) to complete the rolling review process to facilitate the final marketing authorization application (MAA).
As part of the rolling review, the CHMP has begun evaluating data generated in preclinical trials. The formal MAA submission could be finalized following the rolling-review process, pending demonstration of vaccine efficacy and safety and confirmation from the EMA that the submitted data are adequate.
BNT162b2 is based on BioNTech’s proprietary mRNA technology and is supported by Pfizer’s global vaccine development and manufacturing capabilities. It uses an optimized SARS-CoV-2 full-length spike glycoprotein (S), which is a target of virus neutralizing antibodies. The vaccine candidate is currently being evaluated in a global Phase III study ongoing at more than 120 clinical sites worldwide, including the US, Brazil, South Africa and Argentina.
Lilly Updates Mfg Plans for COVID-19 Monotherapy, Combo Therapy
Eli Lilly and Company has provided an update to its manufacturing plans for a monotherapy and combination therapy involving two SARS-CoV-2 neutralizing antibodies programs, LY-CoV555 (bamlanivimab) and LY-CoV016 (etesevimab). The company also reported positive interim data on the combination therapy in recently diagnosed patients with mild-to-moderate COVID-19.
Lilly has invested in large-scale manufacturing of both antibodies. As a monotherapy, Lilly is focused on a 700-mg dose of LY-CoV555 and anticipates that it could supply as many as one million doses in the fourth quarter of 2020, with 100,000 available in October (October 2020). With respect to the supply of the combination therapy of LY-CoV555 and LY-CoV016, Lilly anticipates it will have 50,000 doses available in the fourth quarter of 2020. The company says that the supply of the combination therapy will increase beginning in the first quarter of 2021 as additional manufacturing resources come on line, including Lilly’s recently announced manufacturing collaboration with Amgen. Lilly says it is also pursuing additional partnerships to provide antibodies to resource-limited countries.
Lilly is engaging with global regulators, including the US Food and Drug Administration, regarding potential emergency use authorization (EUA). The company has submitted an initial request for EUA for the LY-CoV555 monotherapy in higher-risk patients who have been recently diagnosed with mild-to-moderate COVID-19. Lilly says it expect to submit a subsequent request for EUA for the combination therapy in November (November 2020), pending clinical trial enrollment, once additional safety data accumulate and sufficient supply is manufactured. Lilly anticipates having data to support a biologics license application submission for the combination therapy as early as the second quarter of 2021, and says conversations with global regulators are ongoing.
The company also reported data from a new interim analysis that the combination therapy of LY-CoV555 (bamlanivimab) and LY-CoV016 (etesevimab) reduced viral load, symptoms and COVID-related hospitalization and emergency room visits. The Phase II study evaluated LY-CoV555 and LY-CoV016 in symptomatic COVID-19 patients in the outpatient setting.
Lilly is proceeding with other trials. It is studying lower doses of the combination therapy and alternative delivery options in planned or ongoing clinical trials. Other ongoing clinical trials include a Phase III study of the LY-CoV555 monotherapy for the prevention of COVID-19 in residents and staff at long-term care facilities. In addition, the LY-CoV555 monotherapy is being tested in the National Institutes of Health-led studies of ambulatory and hospitalized COVID-19 patients.
Lilly says it also plans to initiate a pragmatic, open-label study in the coming weeks (as reported on October 7, 2020) by enrolling patients treated with either the monotherapy or combination therapy with a focus on collecting data regarding hospitalizations, deaths, and safety.
Source: Eli Lilly and Company
Lilly in Pact for Supply of Potential COVID-19 Anitbody Therapy
Eli Lilly and Company has entered into an agreement with the Bill & Melinda Gates Foundation to facilitate access to future Lilly therapeutic antibodies under development for the prevention and treatment of COVID-19 to benefit low- and middle-income countries.
This effort is part of the COVID-19 Therapeutics Accelerator, an initiative launched by the Gates Foundation, Wellcome, and Mastercard to speed the development of and access to therapies for COVID-19.
Commercial manufacturing will commence in April 2021 at Fujifilm Diosynth Biotechnologies’ facility in Denmark, where the Therapeutics Accelerator reserved manufacturing capacity in an agreement announced in April (April 2020). Lilly says it has already started the manufacturing technology transfer at risk, in anticipation of regulatory authorization for its antibody therapy. Lilly says it will make certain volumes of its antibody therapeutic manufactured in other facilities available to lower-income countries prior to April 2021, pending the timing of regulatory authorization. Lilly and its collaboration partners will continue to be responsible for research and development of the product.
Lilly’s collaborators, AbCellera Biologics, Shanghai Junshi Biosciences, and Columbia University have agreed to waive their royalties on Lilly therapeutic antibodies distributed in low- and middle-income countries as part of this initiative.
Source: Eli Lilly and Company
Gilead in US Distribution for COVID-19 Drug Remdesivir; In EU Pact
Gilead Sciences reported that starting October 1, 2020, it is responsible for distributing its COVID-19 treatment, Veklury (remdesivir), thereby removing the US government’s role in directing the allocation of the drug. The company also signed a pact with the European Commission for the supply of the drug in Europe.
In the US, AmerisourceBergen, a US drug wholesaler and distributor, will continue to serve as the sole US distributor of Veklury through the end of 2020 and will sell the product directly to hospitals. Gilead says this distribution model closely reflects the traditional model hospitals use to procure medicines. Hospitals will control the quantity of Veklury that they order and enable them to have ample, predictable supply of Veklury in advance of any anticipated increase in COVID-19 incidence.
The change in the allocation model from the US government to Gilead follows data from the US Department of Health and Human Services (HHS) that showed that the current supply of Veklury exceeds market demand. Records from the HHS’ Office of the Assistant Secretary for Preparedness and Response (ASPR) indicate that of the 500,000 treatment courses made available in the US between July and September 2020, state and territorial health departments accepted 84% of their allocations (423,765 treatment courses), but only 32% (160,981 treatment courses) of the total allocation was actually purchased by hospitals in their jurisdictions. Over the course of the project, ASPR allocated over 700,000 treatment courses, which included the reallocation of 200,000 treatment courses that were not initially accepted by state and territorial health departments.
The HHS says the cost of Veklury will not change in the transition from US government oversight of allocation to direct commercial sales. Hospitals will continue to pay no more than Gilead’s wholesale acquisition price, approximately $3,200 per treatment course.
The US Food and Drug Administration expanded the emergency use authorization enabling use of Veklury to treat all hospitalized patients with COVID-19, in addition to the previous authorization for patients hospitalized with severe COVID-19.
In a separate development, Gilead and the European Commission have signed a joint procurement agreement to enable participating countries in the EU and the European Economic Area (EEA) and the UK to purchase Veklury for both real-time demand and stockpiling needs, coordinated by the European Commission. The agreement covers purchases of Veklury over the next six months (as reported on October 8, 2020) and has the option to be extended. In the EU, EEA and UK, Veklury is indicated for the treatment of COVID-19 in adult and adolescent patients with pneumonia requiring supplemental oxygen.
GSK, Vir Biotechnology Expand Phase III Study of COVID-19 Drug
GlaxoSmithKline and Vir Biotechnology, a San Francisco-based clinical-stage biopharmaceutical company, are expanding globally a Phase III study for the companies’ monoclonal antibody, VIR-7831 (also known as GSK4182136), for the early treatment of COVID-19 in patients who are at high risk of hospitalization.
The companies formed a collaboration earlier this year (April 2020), which included a $250-million equity investment in Vir by GSK, to research and develop treatments for COVID-19.
VIR-7831 is a fully human anti-SARS-CoV-2 monoclonal antibody that was selected based on its potential to neutralize the virus, kill infected cells, provide a high barrier to resistance, and achieve high concentrations in the lungs. The registrational study will now expand globally to include additional sites in North America, South America and Europe following a positive assessment of unblinded safety data from the lead-in portion of the trial by an independent data monitoring committee on September 30, 2020.
The Phase III portion of the study will assess the single intravenous infusion of VIR-7831 or placebo in approximately 1,300 non-hospitalized participants globally. The companies say interim analyses are planned to evaluate safety, futility, and efficacy with initial results that may be available as early as the end of 2020. Results for the primary endpoint are expected in the first quarter of 2021, with current estimates at January 2021. The primary efficacy endpoint is the proportion of patients who have progression of COVID-19 as defined by the need for hospitalization or death.
The clinical development program for VIR-7831 also includes two additional planned trials: one for the treatment of hospitalized patients and another for the prevention of symptomatic infection. The companies say they expect to start a Phase Ib/IIa trial in the second half of 2020 evaluating VIR-7832, a second investigational SARS-CoV-2 neutralizing antibody that shares the same characteristics as VIR-7831, plus enhanced effector function, which may confer additional efficacy in treatment or prophylaxis by stimulating a T-cell response.
Regeneron’s Reports Positive Results of COVID-19 Antibody Cocktail
Regeneron Pharmaceuticals, a Tarrytown, New York-based biopharmaceutical company, reports positive first data from a descriptive analysis of a Phase I/II/III trial of its investigational antibody cocktail against COVID-19, REGN-COV2.
The company says data showed REGN-COV2 reduced viral load and the time to alleviate symptoms in non-hospitalized patients with COVID-19. REGN-COV2 also showed positive trends in reducing medical visits. The trial is measuring the effect of adding REGN-COV2 to usual standard-of-care compared to adding placebo to standard-of-care. This trial is part of a larger program that also includes studies of REGN-COV2 for the treatment of hospitalized patients, and for the prevention of infection in people who have been exposed to COVID-19 patients.
At least 1,300 patients will be recruited into the Phase II/III portion of the outpatient trial overall. In addition to this trial in non-hospitalized patients, REGN-COV2 is currently being studied in a Phase II/III clinical trial for the treatment of COVID-19 in hospitalized patients, a Phase III open-label trial of hospitalized patients in the UK, and a Phase III trial for the prevention of COVID-19 in household contacts of infected individuals. Regeneron says recruitment in all four trials is ongoing.
Eisai in Joint Development Pact for COVID-19 Therapeutics
Eisai has entered into a joint research agreement with four research organizations in Japan for a research project for the research and development of innovative treatments for COVID-19.
This joint research project is with the KAN Research Institute, the National Center for Global Health and Medicine, Nagasaki University, and Yokohama City University. It is part of a call by the Japan Agency for Medical Research and Development for the research and development of innovative treatments for emerging and re-emerging infectious diseases.
In the research project, a non-clinical animal model of SARS-CoV-2 infection, the virus that causes COVID-19, will be constructed. Additionally, eritoran, a toll-like receptor antagonist, discovered by Eisai, and an anti-FKN (fractalkine) antibody, E6011, discovered by Eisai’s research subsidiary, the KAN Research Institute, will be evaluated. In addition, the project will promote biomarker research using clinical samples derived from SARS-CoV-2 infected patients.
Mapi Pharma Dedicates Fill–Finish Capacity for COVID-19 Vaccines
Mapi Pharma, a late-stage clinical development biopharmaceutical company based in Ness Ziona, Israel, reports it will dedicate manufacturing capacity at its facility in Jerusalem for sterile injectable finished dosage forms for COVID-19 vaccines for supply to Israel, the European Union (EU), and globally.
Mapi is currently expanding its Jerusalem fill–finish facility, which was originally established by Johnson & Johnson (J&J). Over $100 million has been invested in the facility, which was built to supply J&J’s own needs of sterile products. Mapi is now adding a new line for sterile filling and finishing of liquids and powders for injections to the facility, which will support the global effort to bring a COVID-19 vaccine, once approved, to Israeli and EU citizens and potentially to other countries.
Source: Mapi Pharma
FDA Awards Research Contract for SARS-CoV-2 Analysis
The US Food and Drug Administration (FDA) has awarded a new research contract to the Stanford University School of Medicine to perform an in-depth analysis of tissue samples to learn more about how SARS-CoV-2, the virus that causes COVID-19, affects different systems in the body, and identify immune correlates. The FDA says this regulatory science project could potentially help inform development and evaluation of medical countermeasures for COVID-19.
Source: US Food and Drug Administration
CEPI Establishes Global Lab Network for COVID Vaccine Assessment
The Coalition for Epidemic Preparedness Innovations (CEPI), a public–private partnership focused on vaccine development against emerging infectious diseases, has partnered with five clinical sample testing laboratories to create a centralized global network to assess and compare the immunological responses generated by COVID-19 vaccine candidates.
Located across multiple global regions, the laboratories initially selected for this vaccine-assessment network are: Nexelis in Canada; Public Health England (PHE) in the UK; VisMederi Srl in Italy; Viroclinics-DDL in the Netherlands, icddr,b (formerly the International Centre for Diarrhoeal Disease Research) in Bangladesh; and Translational Health Sciences and Technological Institute (THSTI) in India.
CEPI says the network will use the same testing reagents, originating in the labs of Nexelis and PHE, and follow common protocols to measure the immunogenicity of multiple COVID-19 vaccine candidates (both CEPI-funded and non-CEPI funded developers). CEPI says it is actively negotiating with additional laboratories to participate in this network. The samples from participating vaccine developers will instead be tested in the same group of laboratories using the same methods, therefore, removing much of the inter-laboratory variability and allowing for head-to-head comparisons of immune responses induced by multiple vaccine candidates.