Pharma COVID Roundup: News from Novartis, Moderna, Gilead, Lilly

The latest on manufacturing and potential treatments for COVID-19 with news from Novartis, Moderna, Gilead, Lilly, Sun Pharma, and WHO

Novartis Signs Manufacturing Pact for COVID-19 Vaccine Candidate
Massachusetts Eye and Ear and Massachusetts General Hospital have entered into a manufacturing agreement with AveXis, a Bannockburn, Illinois-based Novartis company, to produce an investigational COVID-19 vaccine, AAVCOVID, based on adeno-associated viruses (AAV) gene-transfer technology.

AveXis began manufacturing the vaccine last month (as reported on May 28, 2020) while AAVCOVID undergoes further safety and efficacy testing in preclinical studies taking place at academic medical institutions, including Massachusetts Eye and Ear. AveXis will lead the manufacturing efforts of the new vaccine and use its AAV technology. AveXis is contributing its technology, expertise, and supply chain at no cost to supply the AAV vaccine for COVID clinical trials that are scheduled to begin in the second half of 2020.

The AAVCOVID vaccine program uses an AAV vector to deliver the genetic code to produce protein fragments of the SARS-CoV-2 virus, the virus that causes COVID-19, to elicit an immune response. Once early studies are completed, including the first clinical trials intended to establish safety and efficacy of the experimental vaccine, the researchers say they aim to advance the study into later phases. AveXis has the option to manufacture the AAV vaccine for additional clinical development, registration and/or commercial activities.

Massachusetts Eye and Ear and Massachusetts General are member hospitals of Massachusetts General Brigham.

Source: Massachusetts Eye and Ear

Moderna Doses First Patients in Phase II COVID-19 Vaccine Study
Moderna, a clinical-stage biopharmaceutical company developing messenger RNA (mRNA) therapeutics and vaccines, has dosed the first participants in each age cohort in the company’s Phase II study of its mRNA vaccine candidate, mRNA-1273, against SARS-CoV-2, the virus that causes COVID-19.

The Phase II study, being conducted by Moderna under its own investigational new drug application, will evaluate the safety, reactogenicity and immunogenicity of two vaccinations of mRNA-1273 given 28 days apart. The company says it intends to enroll 600 healthy participants across two cohorts of adults ages 18-55 years, and older adults ages 55 years and above.

On May 6, 2020 the US Food and Drug Administration (FDA) completed its review of the company’s investigational new drug application for mRNA-1273, and on May 12 2020, the FDA granted it fast-track designation. On May 18 2020, Moderna announced initial data from the Phase I study of mRNA-1273 led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The NIH will be submitting the Phase I data to a peer-reviewed clinical publication. Moderna says it anticipates collaborating with NIAID to implement a Phase III study and expects Phase III trial initiation in July 2020, subject to finalization of the clinical trial protocol.

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.

Source: Moderna

Gilead’s Results from Antiviral Phase III Trial for COVID-19 Patients
Gilead Sciences announced topline results from a Phase III trial in hospitalized patients with moderate COVID-19 pneumonia that evaluated 5-day and 10-day courses of the company’s investigational antiviral drug, remdesivir, plus standard of care, versus standard of care alone.

The study demonstrated that patients in the 5-day remdesivir treatment group were 65% more likely to have clinical improvement at Day 11 compared with those in the standard of care group. The company says the odds of improvement in clinical status with the 10-day treatment course of remdesivir versus standard of care were also favorable, trending toward but not reaching statistical significance. No new safety signals were identified with remdesivir across either treatment group. Gilead says it plans to submit the full data for publication in a peer-reviewed journal in the coming weeks (as reported on June 1, 2020).

At Day 11, Gilead says a higher proportion of patients in the 5-day treatment group achieved improvement in clinical status versus the standard of care group. Additionally, non-statistically significant increases in clinical worsening or death were observed in the standard of care only group compared with the remdesivir groups.

Remdesivir is currently approved in Japan as a treatment for patients infected with SARS-CoV-2, the virus that causes COVID-19. Outside of Japan, remdesivir is an investigational, unapproved drug. The US Food and Drug Administration granted remdesivir an emergency use authorization for the treatment of hospitalized patients with severe COVID-19. The authorization is temporary and does not take the place of the formal new drug application submission, review and approval process.

Source: Gilead Sciences

Lilly Begins Study of Potential COVID-19 Antibody Treatment
Eli Lilly and Company has dosed the first patients in a clinical study of a potential antibody treatment against COVID-19. The investigational medicine, LY-CoV555, is the first to emerge from its previously announced collaboration with AbCellera, a Vancouver, British Columbia, Canada-based biopharmaceutical company, to create antibody therapies for the prevention and treatment of COVID-19.

Lilly scientists developed the antibody in three months after AbCellera and the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases identified it from a blood sample taken from one of the first US patients who recovered from COVID-19. The drug is specifically designed to attack SARS-CoV-2, the virus that causes COVID-19.

The first patients in the study were dosed at major medical centers in the US, including New York University’s Grossman School of Medicine and Cedars-Sinai in Los Angeles.

If Phase I results show the antibody can be safely administered, Lilly says it expects to move into the next phase of testing by studying LY-CoV555 in non-hospitalized COVID-19 patients. The company also says it plans to study the drug in a preventative setting and focus on vulnerable patient populations who historically are not optimal candidates for vaccines.

Lilly says it is researching multiple approaches to treating COVID-19, and existing Lilly medicines are being studied to understand their potential in treating complications of COVID-19. The company is collaborating with two biotech companies to discover novel antibody treatments for COVID-19.

Source: Eli Lilly and Company

WHO To Resume Trials of Hydroxychloroquine for Treating COVID-19
The World Health Organization (WHO) announced this week (June 3, 2020) that it is resuming its clinical trials that use hydroxychloroquine, a drug approved for treating malaria, lupus, and rheumatoid arthritis that is being evaluated to treat COVID-19. 

Late last month (May 2020), WHO reported that it was temporarily suspending clinical trials as a precaution over the risk/benefit profile of the drug following publication of findings in The Lancet, a medical journal, that COVID-19 patients receiving hydroxychloroquine or chloroquine did not achieve better outcomes and had decreased in-hospital survival rates. The findings were based on a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide antibiotic for the treatment of COVID-19.

This week (June 4, 2020), the authors of the Lancet article issued a retraction since they could no longer vouch for the veracity of the primary data. They said that their independent peer reviewers informed them that were not able to conduct an independent and private peer review due to limitations in accessing the full dataset due to confidentially issues and they notified the authors of their withdrawal from the peer-review process.

As a result, in a press briefing this week (June 3, 2020), WHO reported a data and safety monitoring committee has been reviewing data and recommended that there are no reasons to modify the trial protocol. The WHO has 3,500 patients from 17 countries enrolled in a global clinical trial, the Solidarity Trial, in which one arm of the trial was evaluating hydroxychloroquine in COVID-19 patients.

The WHO’s executive group received this recommendation and endorsed the continuation of all arms of the Solidarity trial, including hydroxychloroquine, and will communicate with the principal investigators in the trial about resuming the hydroxychloroquine arm of the trial.

Source: World Health Organization

EMA Updates Use of Potential COVID-19 Drugs, Chloroquine, Remdisivir
The European Medicines Agency (EMA) is reminding healthcare professionals to monitor patients with COVID-19 who are receiving chloroquine or hydroxychloroquine, which are authorized for malaria and certain autoimmune diseases.

Both chloroquine and hydroxychloroquine have been used to treat patients with COVID-19, but their beneficial effects in this patient population are not established, according to the EMA. Several observational studies in COVID-19 have reported that chloroquine and hydroxychloroquine are associated with an increased risk of heart problems, including cardiac arrhythmias and cardiac arrest. 

In view of the emerging data, the EMA says some EU countries have suspended or stopped clinical trials investigating chloroquine and hydroxychloroquine in COVID-19 patients. The EMA says that while further analyses of available data are being carried out, chloroquine and hydroxychloroquine should only be used in clinical trials for treatment or prophylaxis of COVID-19 or in national emergency-use programs in hospitalized patients under close supervision.

In a separate development, the EMA’s Committee for Medicinal Products for Human Use (CHMP), discussed the status of the review of Gilead Sciences’ investigational antiviral, remdesivir, for treating patients with COVID-19.

On April 30, 2020, the CHMP started a rolling review of data with the first cycle being concluded on May 15, 2020. The CHMP requested some further data and says the next step would be for the company to submit this data together with an application for a conditional marketing authorization.

The EMA says the company has not yet submitted an application, but it is expected to do so shortly (as reported on May 29, 2020). Once an application has been submitted, the CHMP says it will assess it under a timeline which will be reduced to the absolute minimum to still allow for a thorough evaluation of benefits and risks, which meaning an opinion could come soon depending on the robustness of the data submitted.

Source: European Medicines Agency (chloroquine) and European Medicines Agency (remdesivir)

Sun Pharma To Initiate Clinical Trial for COVID-19 Drug
Sun Pharmaceutical Industries, a Mumbai, India-based pharmaceutical company, has received approval from the Drugs Controller General of India, the country’s national pharmaceutical regulatory agency, to initiate a clinical trial of nafamostat mesylate, a synthetic serine protease inhibitor, in COVID-19 patients. Nafamostat is approved in Japan for improvement of acute symptoms of pancreatitis and treatment of disseminated intravascular coagulation.

The company says a group of scientists from the University of Tokyo in Japan and the Leibniz Institute for Primate Research in Germany have recently demonstrated that nafamostat, at very low concentrations, suppresses a protein, TMPRSS2, which the COVID-19 virus uses to enter human lung cells. Another group from the Institut Pasteur Korea in South Korea also published data comparing antiviral efficacy of 24 drugs and nafamostat against SARS-CoV-2, the virus that causes COVID-19, in in-vitro studies in human lung epithelial derived cells. In this research, nafamostat was shown to inhibit virus entry at very low concentrations, consistent with findings from Japan and German labs, according to information from Sun Pharma.

Sun Pharma says globally, there are three clinical trials currently underway to test nafamostat in COVID-19 patients: (1) by the University of Tokyo Hospital in Japan; (2) by the Gyeongsang National University Hospital in South Korea; and (3) a collaborative trial by University Hospital in Padova, Italy, the University of Zurich in Switzerland and Yokohoma City University in Japan.

Sun Pharma says it plans to initiate the clinical trials. The company has initiated manufacturing of both the API and the finished product of nafamostat in India, using technology from its subsidiary, Pola Pharma Japan.

Source: Sun Pharmaceutical Industries

University of Maryland Researchers Develop Experimental COVID-19 Test
Scientists from the University of Maryland School of Medicine (UMSOM) have developed an experimental diagnostic test for COVID-19 that can visually detect the presence of the virus in 10 minutes, according to the university.

The UMSOM says the experimental diagnostic test uses a simple assay containing plasmonic gold nanoparticles to detect a color change when the virus is present. The test does not require the use of any advanced laboratory techniques, such as those commonly used to amplify DNA, for analysis. The authors published their work in the American Chemical Society’s nanotechnology journal, ACS Nano.

The researchers specify that once a nasal swab or saliva sample is obtained from a patient, the RNA is extracted from the sample via a simple process that takes about 10 minutes. The test uses a highly specific molecule attached to the gold nanoparticles to detect a particular protein. This protein is part of the genetic sequence that is unique to COVID-19. When the biosensor binds to the virus’s gene sequence, the gold nanoparticles respond by turning the liquid reagent from purple to blue.

Study leader Dipanjan Pan, PhD, Professor of Diagnostic Radiology and Nuclear Medicine and Pediatrics at the UMSOM created a company called VitruVian Bio to develop the test for commercial application. UMSOM says he plans to have a pre-submission meeting with the US Food and Drug Administration within the next month (as reported on May 28, 2020) to discuss requirements for getting an emergency use authorization for the test.

Source: University of Maryland School of Medicine

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