Pharma COVID Roundup: News from Novartis, Pfizer, and AstraZenecaBy
The latest from pharma companies on potential COVID-19 treatments with news from Novartis, Pfizer, AstraZeneca, Biogen, Bayer, Alexion, Fujifilm, and Celltrion.
News from Novartis, Pfizer, AstraZeneca, Biogen and Bayer
Novartis Sponsors Phase III Clinical Trial of Potential COVID Drug
Novartis has reached an agreement with the US Food and Drug Administration (FDA) to proceed with a Phase III clinical trial with approximately 440 patients to evaluate the use of hydroxychloroquine, now indicated for the treatment of malaria and certain autoimmune diseases, for the potential treatment of hospitalized patients with COVID-19. The clinical trial drug supply will be provided by Sandoz, the generics and biosimilars division of Novartis.
The trial sponsored by Novartis will be conducted at more than a dozen sites in the US. Novartis plans to begin enrollment for this study within the next few weeks (as reported on April 20, 2020) and says it will be reporting results as soon as possible. To help achieve broad access to hydroxychloroquine, Novartis says it will make any intellectual property that relates to the use of hydroxychloroquine to treat or prevent COVID-19 available through non-exclusive voluntary licenses, appropriate waivers, or similar mechanisms.
Patients in the trial will be randomized into three groups. The first group will receive hydroxychloroquine. The second group will receive hydroxychloroquine in combination with azithromycin, which is an antibiotic therapy. The third group will receive placebo.
In addition to the clinical trial, Novartis, through Sandoz, says it will donate up to 130 million tablets of hydroxychloroquine to supply clinical research efforts in the event the medicine is proven beneficial in the treatment of COVID-19. Sandoz has already donated 30 million tablets to the US Department of Health and Human Services and is dispatching shipments to countries based on requests from governments.
As part of its research and development, Novartis has formed a clinical investigation team to provide access for approved clinical requests and clinical evaluation of its medicines to be repurposed and address patients with COVID-19. In addition to hydroxychloroquine, Novartis says it plans to sponsor or co-sponsor clinical trials to study ruxolitinib and canakinumab for hospitalized patients with COVID-19 infections. Requests for investigator-initiated trials have been granted for COVID-19-related clinical studies of ruxolitinib, canakinumab, imatinib mesylate, secukinumab, hydroxychloroquine, and valsartan.
Pfizer, BioNTech OK’d for Phase I/II Trial of COVID Vaccine Candidates
Pfizer and BioNTech, Mainz, Germany-based biopharmaceutical company, have received approval from the Paul-Ehrlich-Institut, the Federal Institute for Vaccines and Biomedicines in Germany, for a Phase I/II clinical trial for BioNTech’s COVID-19 vaccine program (BNT162) to prevent COVID-19 infection, which BioNTech and Pfizer are jointly developing. Earlier this month (April 2020), Pfizer and BioNTech formed a collaboration, worth up to $748 million ($185 million upfront), to develop vaccine candidates against COVID-19.
The companies say the trial is the first clinical trial of a COVID-19 vaccine candidate to start in Germany. Pfizer and BioNTech say they will also conduct trials for the BNT162 program in the US upon regulatory approval.
The four vaccine candidates represent different mRNA formats and target antigens. Two of the four vaccine candidates include a nucleoside modified mRNA (modRNA), one includes a uridine containing mRNA (uRNA), and the fourth vaccine candidate uses self-amplifying mRNA (saRNA). Each mRNA format is combined with a lipid nanoparticle formulation. The larger spike sequence is included in two of the vaccine candidates, and the smaller optimized receptor binding domain (RBD) from the spike protein is included in the other two candidates. The RBD-based candidates contain the piece of the spike that is thought to be for eliciting antibodies that can inactivate the virus.
During the clinical development stage, BioNTech says it will provide its partners clinical supply of the vaccine from its GMP-certified mRNA manufacturing facilities in Europe. BioNTech is also collaborating with Fosun Pharmaceutical, a Shanghai, China-based healthcare company, to develop BNT162 in China, where the companies expect to conduct trials.
AstraZeneca Initiates Phase III Trial of Diabetes Drug for COVID-Related Cardio Effects
AstraZeneca and Saint Luke’s Mid America Heart Institute, a Kansas City, Missouri-based research institute, have initiated a randomized, global Phase III trial to assess the potential of AstraZeneca’s Farxiga (dapagliflozin), a treatment for Type II diabetes, as a treatment in patients hospitalized with COVID-19 who are at risk of developing serious complications, such as organ failure.
The goal of the trial is to assess whether Farxiga, a sodium-glucose cotransporter 2 inhibitor, can reduce the risk of disease progression, clinical complications, and death due to COVID-19 in patients who also have cardiovascular, metabolic or kidney risk factors.
The trial is open for enrolment in the US and other European countries with a high COVID-19 burden and aims to recruit approximately 900 patients.
Biogen, Broad Institute, Partners HealthCare Launch COVID Biobank
Biogen, the Broad Institute of the Massachusetts Institute of Technology and Harvard University, and Partners HealthCare, a healthcare system and biomedical research organization, have launched a consortium that will build and share a COVID-19 biobank for scientists to study a collection of de-identified biological and medical data to advance knowledge and search for potential vaccines and treatments against COVID-19.
Biogen says it will help employees who wish to volunteer to connect with the project. Biogen employees who contracted and have recovered from COVID-19, as well as people identified as close contacts of those individuals, regardless of whether they were confirmed as having COVID-19, are eligible to participate. Partners HealthCare, Massachusetts General Hospital, and Brigham and Women’s Hospital are coordinating the outreach and sample collection effort.
The collaboration started when several Biogen employees, still recovering from COVID-19, began to consider ways they could contribute their own medical information to research efforts. Biogen leaders reached out to several partners in the hospital and biomedical community, including Deborah Hung, a faculty member of the Broad Institute, where she serves as the Co-Director of the Infectious Disease and Microbiome Program, and a professor in the Departments of Genetics and Medicine at Harvard Medical School in the Divisions of Infectious Disease and Pulmonary and Critical Care and Department of Molecular Biology at Massachusetts General Hospital.
Bayer Partners to Evaluate Potential COVID Treatments
Bayer is partnering with the Population Health Research Institute (PHRI), a Canadian joint research institute of McMaster University and Hamilton Health Sciences, for a clinical research program to identify potential treatments against COVID-19. Two studies will evaluate different combination therapies, including Bayer’s chloroquine and interferon beta-1b.
One study will evaluate the combination of chloroquine with the antibiotic, azithromycin, to see if it prevents deterioration leading to hospital admission. A second study will evaluate the combination of chloroquine with azithromycin, as well as interferon beta-1b, to prevent admission to intensive care, mechanical ventilation and/or death to combat COVID-19. PHRI says it plans to enroll 6,000 patients into the two studies.
Under the pact, Bayer will make a financial commitment of CAD 1.5 million (US $1.1 million) toward the studies and supply study drugs to support the research. This adds to the CAD 500,000 (US $350,000) committed by the PHRI earlier this month (April 2020).
News from Fujifilm, Alexion Pharmaceuticals and Celltrion
Fujifilm Increases Mfg Capacity for Potential COVID-19 Antiviral
Fujifilm has expanded manufacturing capacity at Fujifilm Toyama Chemical, a pharmaceutical subsidiary of Fujifilm, to increase production of Avigan (favipiravir), an antiviral drug for influenza that is being evaluated for treating patients with COVID-19.
Avigan is approved in Japan for as an influenza antiviral drug. It selectively inhibits viral RNA polymerase necessary for influenza virus replication, according to information from the company. Due to this mechanism of action, Avigan may have an antiviral effect on the SARS-CoV-2 coronavirus because like influenza viruses, coronaviruses are single-stranded RNA viruses that also depend on viral RNA polymerase. To determine Avigan’s safety and efficacy to treat COVID-19, Avigan is being evaluated in clinical studies for treating COVID-19.
To increase supply of Avigan, Fujifilm is allocating additional capacity at its Fujifilm Wako Pure Chemical facility in Japan, for production of pharmaceutical intermediates used to manufacture Avigan. In addition, Fujifilm says it has established strategic partnerships with domestic and overseas companies for various manufacturing processes to source raw materials and pharmaceutical substances. Kaneka Corporation, a Tokyo-headquartered chemical company, has reached an agreement with Fujifilm to supply drug substances for Avigan.
Fujifilm expects to increase the monthly production of Avigan up to 100,000 treatment courses by July 2020, approximately 2.5 times more compared to the beginning of March (March 2020), when the company first began its production run. In addition, Fujifilm says it plans to accelerate production up to 300,000 treatment courses by September 2020. A treatment course is a 14-day regimen prescribed by the Japanese Association for Infectious Diseases, which includes two loading doses of 1,800 mg each on the first day of treatment followed by two maintenance doses of 800 mg each on Day 2 through Day 14.
The Japanese government plans to stockpile two million treatment courses of Avigan as part of the Japanese government’s emergency economic package announced on April 7, 2020. Fujifilm says it continues to respond to requests from the Japanese government and will also engage with other countries after consultation with the Japanese government.
Alexion Initiates Phase III Study of Blood Disease Drug for COVID-19
Alexion Pharmaceuticals, a Boston-based biopharmaceutical company, has announced plans to initiate a Phase III study to investigate Ultomiris (ravulizumab-cwvz), which is indicated to treat paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disease that causes red blood cells to break apart, in a subset of adults with COVID-19 who are hospitalized with severe pneumonia or acute respiratory distress syndrome (ARDS).
The study is expected to enroll approximately 270 patients across countries with high numbers of diagnosed cases, beginning in May (May 2020), and will evaluate the impact of Ultomiris, on survival, duration of mechanical ventilation, and hospital stay compared to best supportive care. This follows the US Food and Drug Administration’s (FDA) review and acceptance of Alexion’s investigational new drug (IND) application for Ultomiris for COVID-19.
Source: Alexion Pharmaceuticals
Celltrion To Evaluate Potential COVID Antiviral; Plans to Launch Self-Test Kit
Celltrion, an Incheon, South Korea-based biopharmaceutical company developing innovator drugs and biosimilars, reported on March 23, 2020 it had completed the first step of developing an antiviral treatment to address COVID-19 and plans to launch a rapid self-testing diagnostic kit that could provide results within 15-20 minutes.
Celltrion has been selected by the Korea Centers for Disease Control as a developer for a monoclonal antibody project to treat and prevent COVID-19. The company has identified a library of antibodies sourced from the blood of recovered patients in Korea, which are thought to be involved in neutralizing the virus and may contribute to recovery from COVID-19. Celltrion says these antibodies are undergoing a further screening processes to identify those that are effective in neutralizing the virus causing COVID-19. Once identified, these antibodies will form the basis of the antiviral treatment to be tested through preclinical and clinical trials in the third quarter of 2020.
Celltrion also says it plans to launch a rapid self-testing diagnostic kit in the summer of 2020. The kit will focus on the gene that encodes the surface spike (S) protein, a glycoprotein for viral entry into human host cells. The kit is designed to show results within 15-20 minutes. Once it has gained a CE mark, a certification mark that indicates conformity with health, safety, and environmental protection standards for products sold within the European Economic Area, the rapid self-testing diagnostic kit will become available in Europe through Celltrion Healthcare. Celltrion says it plans to apply for device authorization from the US Food and Drug Administration and other regulatory authorities after acquiring relevant data.