Pharma COVID Roundup: News from Sanofi, Mylan, GSK and CSL BehringBy
The latest on manufacturing and potential treatments for COVID-19 with news from Sanofi, Mylan, GSK, Moderna, CSL Behring, CureVac, Sinovac, Zydus Cadila, and the WHO.
News from Sanofi, Mylan, GSK, Moderna, CSL Behring
Sanofi, Regeneron End US Trial of COVID-19 Drug Candidate
Sanofi and Regeneron Pharmaceuticals, a Tarrytown, New York-based biopharmaceutical company, have stopped the US Phase III trial of Kevzara (sarilumab) 400 mg, a drug indicated for treating adults with moderately to severely active rheumatoid arthritis, in COVID-19 patients requiring mechanical ventilation.
The companies report that COVID-19 patients requiring mechanical ventilation did not meet the study’s primary and key secondary endpoints when Kevzara was added to best supportive care compared to best supportive care alone (placebo).
Sanofi says minor positive trends were observed in the primary pre-specified analysis group (critical patients on Kevzara 400 mg who were mechanically ventilated at baseline) that did not reach statistical significance and these were countered by negative trends in a subgroup of critical patients who were not mechanically ventilated at baseline. Based on the results, the US-based trial has been stopped, including in a second cohort of patients who received a higher dose of Kevzara (800 mg).
A separate Sanofi-led trial outside of the US in hospitalized patients with severe and critical COVID-19 using a different dosing regimen is ongoing. The same Independent Data Monitoring Committee is overseeing both the Regeneron-led US trial and the Sanofi-led trial outside of US, which has recommended that the trial outside of the US continue. The companies say results are expected to be reported in the third quarter of 2020.
Source: Sanofi and Regeneron Pharmaceuticals
Mylan Secures Approval for Remdesivir in India for COVID-19
Mylan reports that the Drug Controller General of India (DCGI) has approved its version of remdesivir, an investigational antiviral drug from Gilead Sciences, 100 mg/vial, for restricted emergency use in India as part of the DCGI’s accelerated approval process to address COVID-19.
In May (May 2020), Mylan formed a global collaboration agreement with Gilead for the commercialization of remdesivir in 127 low- and middle-income countries, including India.
The drug was approved for treating suspected or laboratory confirmed incidences of COVID-19 in adults and children hospitalized with severe presentations of the disease. It is being launched under the brand name Desrem in India and will be available to patients in July (as reported on July 6, 2020) at a price of INR 4,800 ($64). Mylan says it will manufacture remdesivir in India at its injectables facilities and will continue to work toward expanding emergency use access for patients in the 127 low- and middle-income countries under its licensing deal with Gilead Sciences, subject to reviews by national regulatory bodies and the Prequalification Program of the World Health Organization.
The approval by DCGI in India represents the first for Mylan in its pact with Gilead for remdesivir in these 127 countries. Remdesivir is the tenth medicine licensed to Mylan by Gilead, who signed their first agreement in 2006 for the HIV medicine, tenofovir disoproxil fumarate.
GSK, Medicago in Pact to Develop COVID-19 Vaccine Candidate
GlaxoSmithKline (GSK) and Medicago, a Quebec-based biopharmaceutical company, have formed a collaboration to develop and evaluate a COVID-19 candidate vaccine that combines Medicago’s recombinant coronavirus virus-like particles (CoVLP) with GSK’s pandemic adjuvant system.
CoVLPs mimic the structure of the virus responsible for COVID-19 disease and are recognized by the immune system. The use of an adjuvant may boost the immune response and reduce the amount of antigen required per dose, thereby allowing more vaccine doses to be produced.
Phase I clinical testing is planned to start in mid-July (July 2020) and will evaluate three different dose levels of antigen combined with GSKs pandemic adjuvant and in parallel with an adjuvant from another company (Dynavax), administered on a one- and two-dose vaccination schedule, given 21 days apart. In a separate announcement, Medicago reports that it has partnered with Dynavax, a Berkeley, California-based vaccines company, to evaluate Medicago’s CoVLP vaccine candidate with Dynavax’s advanced adjuvant, CpG 1018TM, an adjuvant contained in Dynavax’s FDA-approved adult hepatitis B vaccine.
Subject to successful clinical development and regulatory considerations, the companies say they aim to complete development and make the vaccine available in the first half of 2021. Medicago will also evaluate expanding its separate collaborations with GSK and Dynavax for other opportunities.
The companies will use Medicago’s plant-based production platform to manufacture the COVID-19 vaccine antigen, which uses the leaves of a plant as bioreactors to produce the S-spike protein, which self-assemble into VLPs for use in the vaccine candidate. Using this technology, combined with the proprietary adjuvant systems, the companies say they expect to be able to manufacture approximately 100 million doses by the end of 2021. By the end of 2023, a large-scale facility under construction by Medicago in Quebec City, Canada, is expected to deliver up to 1 billion doses annually. The manufacturing platform has been used to produce a seasonal VLP flu vaccine and the license application is under review with Canadian regulatory authorities. In addition, upon completion of ongoing scale-up activities, the existing equipment capacity for Dynavax’s CpG 1018 adjuvant will be 600 million to 1.2 billion adjuvant doses annually, depending on the final dose selected.
Source: GlaxoSmithKline, Medicago (GSK), Medicago (Dynavax) and Dynavax
Moderna Completes Enrollment of Phase II Study of COVID-19 Vaccine
Moderna, a clinical-stage biopharmaceutical company developing messenger RNA (mRNA) therapeutics and vaccines, has completed enrollment for both cohorts (younger adults and older adults) of a Phase II study of mRNA-1273, the company’s mRNA vaccine candidate against COVID-19.
In addition, Moderna has finalized the protocol for a Phase III study protocol based on feedback from the US Food and Drug Administration. The Phase III rial is expected to begin this month (July 2020) in the US and include approximately 30,000 participants at a 100-µg dose and be conducted in collaboration with the National Institute of Allergy and Infectious Diseases, subject to regulatory approval.
Moderna has completed manufacture of vaccine required to start the Phase III study. With the Phase III dose at 100 μg, the company 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. In addition, Moderna recently announced a collaboration with Catalent for large-scale, commercial fill-finish manufacturing of mRNA-1273 at Catalent’s biologics facility in Indiana.
CSL Begins Trial for Monoclonal Antibody for COVID-19
CSL Behring reports that the first patient has been enrolled in its Phase II study to assess CSL312 (garadacimab, FactorXIIa antagonist monoclonal antibody) to treat patients with respiratory distress, a cause of death in patients with COVID-19-related pneumonia.
The multicenter, double-blind, placebo-controlled study, consisting of approximately 124 adult patients testing positive for SARS CoV-2, the virus that causes COVID-19, will be randomized to receive either CSL312 or placebo, in addition to standard of care treatment. The primary endpoint being evaluated is the incidence of tracheal intubation or death.
Overall, CSL is evaluating five approaches across its plasma fractionation and recombinant and antibody scientific platforms for preventing and treating COVID-19.
Source: CSL Behring
News from CureVac, Sinovac, Zydus Cadila, and the WHO
CureVac Receives $84 M for COVID-19 Vaccine Development and Mfg
CureVac, a Tubingen, Germany-based clinical-stage biopharmaceutical company developing a messenger ribonucleic acid (mRNA) therapeutics, and the European Investment Bank (EIB) have entered into a EUR 75-million ($84-million) loan agreement to support CureVac’s development of vaccines against infectious diseases, including its vaccine candidate, CVnCoV, aimed at preventing SARS-CoV-2, the virus that causes COVID-19.
In addition to supporting development, the EIB loan will support CureVac in completing a new mRNA production facility in Tubingen, Germany. The EIB financing will be provided in three EUR 25-million ($28-million) tranches upon completion of pre-defined milestones.
The transaction is financed under the Infectious Diseases Finance Facility (IDFF) of Horizon 2020, the EU research and innovation program for 2014–2020. The IDFF is a collaboration between the European Commission and the EIB that has supported 13 companies with total lending of EUR 316 million ($357 million) for developing cures, vaccines, and diagnostics against various infectious diseases.
Sinovac’s COVID-19 Vaccine Gets OK for Phase III Trial in Brazil
The Brazilian national regulatory agency, Anvisa, has granted approval for a Phase III clinical trial in Brazil, sponsored by Instituto Butantan, a Brazilian biologic research center, to test the inactivated COVID-19 vaccine developed by Sinovac Life Sciences, a wholly owned subsidiary of Sinovac Biotech, a China-based biopharmaceutical company.
The trial aims to support the licensure of the product and will recruit nearly 9,000 healthcare professionals working in COVID-19 specialized facilities in 12 clinical sites located in several states in Brazil. The inclusion of participants is scheduled to start this month (July 2020) after ethical approval is obtained from each clinical site.
Anvisa’s process review included manufacturing and clinical information generated by Sinovac and a clinical development plan and trial protocol developed by Butantan. The agency fast-tracked the application due to the public health emergency, which took approximately two weeks to conclude.
Zydus Cadila Gets OK for Trial of COVID-19 Vaccine, Drug Candidate
Zydus Cadila, an Ahmedabad, India-based pharmaceutical company, has received approval from the Drug Controller General of India (DCGI) to initiate Phase I/II human clinical trials of its plasmid DNA vaccine candidate for COVID-19, ZyCoV-D. Separately, it also has received approval from the pharmaceutical regulatory authority of Mexico, Cofepris, to start a Phase II trial to evaluate desidustat, an investigational drug for treating anemia in chronic kidney disease, for treating COVID-19.
Zydus’ ZyCoV-D is a plasmid DNA vaccine candidate for COVID-19 developed at its Vaccine Technology Center in Ahmedabad, India. Zydus has manufactured clinical batches of the vaccine candidate and plans to initiate the clinical trials in July 2020 across multiple sites in India in over 1,000 subjects. The company says it intends to ramp up production capacities of ZyCoV-D at multiple sites and facilities to meet demand in India and globally.
For desidustat, clinical and regulatory development for use in COVID-19 is being conducted in Mexico by Avant Santé Research Center, a contract research organization headquartered in Monterrey, Mexico. Zydus will be conducting a Phase IIb, multicenter, open-label, randomized, comparator-controlled study to evaluate the efficacy and safety of desidustat for the management of COVID-19 patients.
Patients infected with COVID-19 have been reported to display signs of hypoxia leading to organ failure and death despite the use of antivirals, anti-inflammatory drugs or ventilators. Desidustat, a hypoxia inducible factor prolyl hydroxylase inhibitor, mimics the physiologic effect of altitude on oxygen availability, according to information from the company. At higher altitudes, the body responds to lower oxygen availability with stabilization of hypoxiainducible factor, and this can lead to increased red blood cell production and improved oxygen delivery to tissues.
Source: Zydus Cadila (India) and Zydus Cadila (Mexico)
WHO Stops Trial for Hydroxychloroquine, Antivirals for COVID-19
The World Health Organization (WHO) has decided to discontinue the arms of a clinical trial (Solidarity Trial) evaluating hydroxychloroquine and lopinavir/ritonavir. The Solidarity Trial was established by the WHO to find an effective COVID-19 treatment for hospitalized patients.
Hydroxychloroquine is a drug approved for treating malaria, lupus, and rheumatoid arthritis that is being evaluated to treat COVID-19. Lopinavir/ritonavir is a fixed-dose combination medication for the treatment and prevention of HIV/AIDS.
The International Steering Committee recommended to stop the trial in light of evidence for hydroxychloroquine versus standard of care and for lopinavir/ritonavir versus standard of care from the Solidarity trial’s interim results and from a review of the evidence from all trials presented at the WHO Summit on COVID-19 research and innovation that was held earlier this month (July 2020).
According to the WHO, these interim trial results show that hydroxychloroquine and lopinavir/ritonavir produce little or no reduction in the mortality of hospitalized COVID-19 patients when compared to standard of care. The WHO says there were also some associated safety signals in the clinical laboratory findings of the add-on Discovery trial, a participant in the Solidarity trial.
The WHO says this decision applies only to the conduct of the Solidarity trial in hospitalized patients and does not affect the possible evaluation in other studies of hydroxychloroquine or lopinavir/ritonavir in non-hospitalized patients or as pre- or post-exposure prophylaxis for COVID-19.
Source: World Health Organization