Pharma COVID Roundup: News from Pfizer, Merck & Co., and Sanofi
The latest from pharma companies on potential COVID-19 treatments with news from Pfizer, Merck & Co., Sanofi, AstraZeneca, Theravance and Inovio.
News from Pfizer, Merck & Co., Sanofi, and AstraZeneca
Pfizer, BioNTech Complete Dosing in Phase I/II Trial of COVID-19 Vaccine
Pfizer and BioNTech, a Mainz, Germany-based immunotherapy company, report that the companies are advancing a vaccine candidate against the novel coronavirus (COVID-19) to clinical trials. Last 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 report that the first cohort of 12 study participants of BioNTech’s Phase I/II clinical trial in Germany have been dosed with the COVID-19 vaccine candidate, BNT162. Dosing in Germany began on April 23, 2020. Pfizer and BioNTech say the companies plan to initiate trials for BNT162 in the US upon regulatory approval.
The study will assess the effects of repeated vaccination following a prime injection for the three vaccine candidates that contain uridine containing mRNA (uRNA) or nucleoside modified mRNA (modRNA). Additionally, a fourth vaccine candidate, which contains self-amplifying mRNA (saRNA), will be evaluated after a single dose of vaccine, and subjects with a higher risk of severe COVID-19 disease will be included in the second part of the study.
BioNTech and Pfizer are jointly developing BNT162. During the clinical development stage, BioNTech says it will provide its partner’s clinical supply of the vaccine from its GMP-certified mRNA manufacturing facilities in Europe. BioNTech is also collaborating with Fosun Pharma, a Shanghai-based biopharmaceutical company, to develop BNT162 in China, where the companies expect to conduct trials.
Merck & Co., Institute for Systems Biology in Pact for COVID Targets
Merck & Co. and the Institute for Systems Biology (ISB), a Seattle-based biomedical research organization, have formed a research collaboration to investigate and define the molecular mechanisms of SARS-CoV-2 infection and COVID-19 and identify targets for medicines and vaccines.
Merck & Co. has also entered into an agreement with the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response within an agency of the US Department of Health and Human Services, for BARDA to provide funding support for this research effort. The company says findings generated from the study will be made available to the worldwide scientific and biomedical community.
Through this collaboration, scientists from ISB, health workers from the Swedish Medical Center, a nonprofit health provider in the greater Seattle area, and a consortium of research organizations and biomedical companies will analyze blood samples and nasal swabs from Swedish Medical Center patients with SARS-CoV-2 using samples from several time points (initial presentation, acute illness, and convalescence). Blood samples will be examined using proteomic, metabolomic, transcriptomics and genetic techniques to evaluate the impact of infection on different organs, and to identify potential biomarkers to predict the risk of severe disease. Additionally, samples will be analyzed to create a profile of the immune response, including quantitative changes in immune cells in patients following SARS CoV-2 infection and characterization of neutralizing antibodies in samples from convalescent patients. These insights can be used to inform vaccine design and antibody therapy.
Under the agreement, Merck & Co. will provide research funding and work with researchers at ISB to characterize targets for potential therapeutic intervention and vaccine development. The study will initially analyze samples from 200 patients with the potential to expand to 300.
Source: Merck & Co.
Sanofi, Regeneron Adjust Trials of Potential COVID Antiviral
Sanofi and Regeneron Pharmaceuticals, a Tarrytown, New York-based biopharmaceutical company, announced the preliminary results from the Phase II portion of an ongoing Phase II/III trial evaluating Kevzara (sarilumab), an antiviral drug, in hospitalized patients with severe or critical respiratory illness caused by COVID-19. Following a review by the Independent Data Monitoring Committee (IDMC) of all available Phase II and Phase III data, the trial will be immediately amended so that only critical patients continue to be enrolled to receive Kevzara 400 mg or placebo.
The companies reported that preliminary analysis of the Phase II portion of the trial demonstrated that Kevzara lowered C-reactive protein, a marker of inflammation, meeting the primary endpoint. Baseline levels of IL-6 were elevated across all treatment arms, with higher levels observed in critical patients compared to severe patients. Additionally, the companies report that no new safety findings were observed with the use of Kevzara in COVID-19 patients.
The companies say analysis of clinical outcomes in the Phase II trial were exploratory and pre-specified to focus on the severe and critical groups. In the preliminary Phase II analysis, Kevzara had no notable benefit on clinical outcomes when combining the severe and critical groups, versus placebo. However, the companies report there were negative trends for most outcomes in the severe group while there were positive trends for all outcomes in the critical group.
Subsequent to the IDMC review, Regeneron and Sanofi conducted a review of the discontinued severe group that revealed the negative trends in Phase II were not reproduced in Phase III, and that clinical outcomes were balanced across all treatment arms.
The ongoing portion of the Phase III trial, which is continuing to enroll patients, currently includes more than 600 patients in the critical group. Regeneron and Sanofi say they remain blinded to the ongoing portion of the Phase III trial and expect to report results by June (June 2020).
In addition, the companies are also conducting a second trial in countries outside of the ;US.The Phase III trial of Kevzara in approximately 400 patients hospitalized with COVID-19 infection is currently enrolling in Italy, Spain, Germany, France, Canada, Russia, Israel, and Japan. Initial results from this second trial are expected in the third quarter of 2020.
AstraZeneca, Oxford University Enter Pact for COVID-19 Vaccine
AstraZeneca and the University of Oxford have formed an agreement for the global development and distribution of the university’s potential recombinant adenovirus vaccine for preventing COVID-19 infection from SARS-CoV-2.
AstraZeneca says this collaboration aims to bring to patients the potential vaccine known as ChAdOx1 nCoV-19, which uses a viral vector based on a weakened version of the common cold (adenovirus) containing the genetic material of the SARS-CoV-2 spike protein. The vaccine candidate is being developed by the Jenner Institute and the Oxford Vaccine Group, at the University of Oxford. Under the agreement, AstraZeneca would be responsible for development and worldwide manufacturing and distribution of the vaccine.
The companies say the potential vaccine entered Phase I clinical trials last week (as reported on April 30, 2020) to study efficacy in healthy volunteers aged 18 to 55 years, across five trial centers in Southern England. AstraZeneca says data from the Phase I trial could be available next month (May 2020) and advancement to late-stage trials should take place by the middle of this year (2020).
The University of Oxford says this partnership comes with £20 million ($25 million) in UK government funding for Oxford University’s vaccine research and support for the institution’s clinical trials.
News from Theravance and Inovio
Theravance Biopharma Initiates Phase I Trial of COVID-19 Drug
Theravance Biopharma, a South San Francisco, California-headquartered biopharmaceutical company, has initiated a Phase I study of TD-0903, a lung-selective, nebulized Janus kinase inhibitor in development for the potential treatment of hospitalized patients with acute lung injury (ALI) caused by COVID-19. The company says TD-0903 has the potential to inhibit the cytokine storm associated with ALI and prevent progression to acute respiratory distress syndrome.
Theravance Biopharma received approval of TD-0903’s initial clinical trial application in the UK for the Phase I study. The purpose of this study is to assess the tolerability and pharmacokinetics of single- and multiple-ascending doses of TD-0903 in healthy volunteers and will enroll up to 54 volunteers.
Upon regulatory review and approval, the program will then initially move to a nested Phase II study in hospitalized patients with COVID-19 in the same clinical setting in the UK.
Source: Theravance Biopharma
Inovio Completes Phase I COVID-19 DNA Vaccine Enrollment
Inovio, a biopharmaceutical company developing DNA-based immunotherapies for cancer and infectious diseases, announced its Phase I US clinical trial for its COVID-19 DNA vaccine candidate, INO-4800, is enrolled with all 40 volunteers receiving their first dose, with interim immune responses and safety results expected in late June (June 2020).
The 40 volunteers, enrolled at sites at the University of Pennsylvania in Philadelphia, Pennsylvania and a clinic in Kansas City, Missouri, will receive two doses of INO-4800 four weeks apart. The company says the Phase I study is designed to assess the profile and immunogenicity of INO-4800 in support of advancing rapidly to a Phase II/III efficacy trial, which is planned to potentially initiate in the summer of 2020.
Working in parallel with the clinical trial program in humans, Inovio says it is conducting several challenge studies in multiple animal models in collaborations with research groups, as well as working to scale up manufacturing of INO-4800. The company also says preclinical data have shown that INO-4800 resulted in promising immune responses across multiple preclinical models, and the company says it is on track with its plan to deliver one million doses by year-end (as reported on April 28, 2020) for additional studies and potential emergency use, pending appropriate regulatory guidance and external funding.