Pharma COVID Roundup: News from Novartis, Moderna, Pfizer, and LillyBy
The latest on COVID-19 vaccines/drugs, manufacturing, and testing from Novartis, Moderna, Pfizer, Lilly, AstraZeneca, Merck & Co., Regeneron, Thermo Fisher, and others.
Manufacturing and supply of COVID-19 vaccines and drugs
Novartis in Pact To Produce API for Roche’s COVID-19 Drug
Novartis has signed an initial agreement with Roche to reserve capacity and implement the technology transfer for the production of tocilizumab, the active pharmaceutical ingredient (API) for Roche’s Actemra/RoActemra, a drug for treating rheumatoid arthritis that is also being tested in various clinical trials investigating its safety and efficacy in treating COVID-19-associated pneumonia.
Under the terms of the initial agreement, the manufacturing process expertise of Roche will be transferred to the Novartis’ biologics drug-substance site in Singapore during the second quarter of 2021. The initial agreement covers the technology transfer and process validation.
This is the third recent manufacturing agreement by Novartis for COVID-19 vaccines and treatments. In March (March 2021), Novartis announced an initial agreement to manufacture the mRNA and bulk drug product for the COVID-19 vaccine candidate from CureVac, a Tubingen, Germany-based clinical-stage biopharmaceutical company, in a new production facility at Novartis’ site in Kundl, Austria. In January (January 2021), Novartis also signed an agreement with BioNTech to provide manufacturing capacity for Pfizer’s/BioNTech’s COVID-19 vaccine at the Novartis site in Stein, Switzerland.
Lilly, US Gov’t Modify Purchase Agreement for COVID-19 Combo Drug
Eli Lilly and Company has announced changes to the purchase agreements with the US government for its neutralizing antibody therapies authorized for emergency use as a treatment for COVID-19.
As part of Lilly’s planned transition to only supply bamlanivimab and etesevimab together, Lilly and the US government have agreed to modify the purchase agreement of bamlanivimab alone and focus on supply of bamlanivimab and etesevimab together. Additionally, the bamlanivimab and etesevimab agreement has been modified to enable the supply of etesevimab to complement doses of bamlanivimab the US government already purchased, some of which have already been delivered to sites of care.
This modified agreement terminates the purchase agreement for bamlanivimab alone and cancels the remaining 350,856 doses that were scheduled to be delivered by the end of March 2021.
Lilly’s bamlanivimab received emergency use authorization from the US Food and Drug Administration. Lilly subsequently developed bamlanivimab and etesevimab for administration together in order to meet the potential challenge of SARS-CoV-2 variants likely to resist treatment with either monoclonal antibody used alone.
Source: Eli Lilly and Company
Moderna Provides Supply, Clinical Updates on COVID-19 Vaccine
Moderna, a biopharmaceutical company developing messenger RNA (mRNA) therapeutics and vaccines, has provided supply updates for its COVID-19 vaccine as well as updated clinical results.
In the fourth quarter of 2020, Moderna delivered approximately 17 million doses of its vaccne to the US government. For the first quarter of 2021, the company delivered approximately 88 million doses to the US government and approximately 14 million doses to other customers. Through April 12, 2021, Moderna cumulatively delivered approximately 132 million doses globally, including approximately 117 million doses to the US government and approximately 15 million doses delivered from Moderna’s ex-US supply chain.
Moderna says it remains on track to deliver the second 100 million doses to the US government by the end of May 2021 followed by another 100 million additional doses by the end of July 2021. The ex-US supply chain was established approximately one quarter behind the US supply chain and continues to ramp up, according to the company.
In a separate development, Moderna expanded its collaboration with Laboratorios Farmacéuticos Rovi of Spain (Rovi), a pan-European pharmaceutical company and CDMO, for the manufacture of the active substance of Moderna’s COVID-19 vaccine. Rovi will install a new line at its facility in Granada, Spain to support production of the active substance of the mRNA vaccine. The new line will have a production capacity equivalent to more than 100 million doses per year and is expected to begin to supply markets outside the US in the third quarter of 2021. Rovi’s support for Moderna’s COVID-19 now includes the manufacture of the active substance, as well as the compounding, filling and final packaging.
Moderna recently reported further efficacy results for its vaccine, including efficacy for COVID-19 variants. In a Phase III study, Moderna reported that updated cases show continued strong efficacy, including greater than 90% against cases of COVID-19 and greater than 95% against severe cases of COVID-19, with approximately six months median follow-up after the second dose.
Additionally, the company reported that new results from a preclinical study of the company’s COVID-19 variant-specific vaccine candidates showed that the company’s variant-specific booster vaccine candidates (mRNA-1273.351 and mRNA-1273.211) increase neutralizing titers against SARS-CoV-2 variants of concern.
Denmark Discontinues Use of AstraZeneca’s COVID-19 Vaccine
The Danish Health Authority has decided to cancel the use of AstraZeneca’s COVID-19 vaccine following reports of rare cases of blood clots. It will continue with the rollout and distribution of COVID-19 vaccines from Pfizer/BioNTech and Moderna.
Denmark was one of several countries that had temporarily suspended the rollout of the AstraZeneca vaccine pending further review by regulatory authorities. Earlier this month (April 2021), the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) reported that a possible link between AstraZeneca’s COVID-19 vaccine and a combination of blood clots and low blood platelets is very rare and reaffirmed that the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.
Denmark further evaluated the vaccine through research and scientific studies, which has included Danish cases, which have been carried out in Denmark under the auspices of ENFORCE, the national cohort study of effectiveness and safety of SARS-CoV-2 vaccines. Danish–Norwegian registry studies revealed higher-than-expected frequency in the number of specific side effects, particularly blood-clotting events occurring in veins in the brain (cerebral venous sinus thrombosis) following vaccination with AstraZeneca’s COVID-19 vaccine.
As a result, the Danish Health Authority reported that it will cancel all booked times and invitations to vaccination with the AstraZeneca’s COVID-19 vaccine. The Danish Health Authority has decided to continue the COVID-19 vaccines rollout without AstraZeneca, but the agency says this does not exclude that it may re-introduce the vaccine at a later date if the situation changes.
Source: Danish Health Authority
Updates on COVID-19 treatments and vaccines
Pfizer, BioNTech Request To Expand COVID-19 Vaccine’ Use to Adolescents
Pfizer and BioNTech, a Mainz, Germany-based immunotherapy company, have requested amendments to the US emergency use authorization of their COVID-19 vaccine to expand the use to adolescents 12 to 15 years of age.
The companies plan to request similar rulings by other regulatory authorities globally in the coming days (as reported on April 9, 2021). These requests are based on data from a Phase III trial in adolescents 12 to 15 years of age with or without prior evidence of SARS-CoV-2 infection, which the companies report that demonstrated 100% efficacy and antibody response after vaccination with the COVID-19 vaccine.
AstraZeneca Reports Trial Data Assessing Diabetes Drug for COVID-19
AstraZeneca reports that a Phase III trial evaluating Farxiga (dapagliflozin), a drug for Type II diabetes, for treating COVID-19-hospitalized patients who are at risk of developing serious complications did not meet its primary endpoints.
The trial did not achieve statistical significance for the primary endpoint of prevention measuring organ dysfunction and all-cause mortality, and the primary endpoint of recovery measuring a change in clinical status (from early recovery to death) at 30 days.
The company says this was the first Phase III trial to evaluate the safety and efficacy of a sodium-glucose co-transporter-2 inhibitor in patients hospitalized with COVID-19 who also have risk factors for developing serious complications, including hypertension, Type II diabetes, atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. Cardiac, renal, and metabolic comorbidities have been associated with poor outcomes and death in patients hospitalized with COVID-19. The full trial results will be presented at the American College of Cardiology Scientific Sessions in May 2021.
Merck & Co. To Discontinue Development of COVID-19 Therapy
Merck & Co. is discontinuing the development of MK-7110, a recombinant fusion protein that targets the innate immune system, in hospitalized COVID-19 patients. Merck gained MK-7110 through its acquisition of OncoImmune, a Rockville, Maryland-based clinical-stage biopharmaceutical company, in a $475-million deal that was announced last year (November 2020).
Merck received feedback from the US Food and Drug Administration that additional data, beyond the study conducted by OncoImmune, would be needed to support a potential emergency use authorization application for MK-7110. Based on the additional research that would be required, new clinical trials, and research related to manufacturing at scale, MK-7110 would not be expected to become available until the first half of 2022. Given this timeline and these technical, clinical, and regulatory uncertainties, Merck decided to discontinue development of MK-7110 for COVID-19 and to focus its efforts on advancing molnupiravir, an oral antiviral agent for the treatment of mild-to-moderate COVID-19 and on producing Johnson & Johnson’s COVID-19 vaccine. Last month (March 2021) Merck formed agreements with J&J and the US government to manufacture J&J’s COVID vaccine.
Merck and Ridgeback Biotherapeutics, a Miami, Florida-based biopharmaceutical company, reported positive Phase II results evaluating molnupiravir in outpatients with COVID-19. The companies will proceed a Phase III study evaluating an 800-mg dose of molnupiravir twice daily. However, the companies will not proceed with a Phase III study evaluating molnupiravir in hospitalized COVID-19 patients as data indicate that molnupiravir is unlikely to demonstrate a clinical benefit in hospitalized patients, who generally had a longer duration of symptoms prior to study entry.
Regeneron Reports Positive Results for COVID-19 Antibody Cocktail
Regeneron Pharmaceuticals, a Tarrytown, New York-based biopharmaceutical company, has reported that a Phase III trial evaluating REGEN-COV, its antibody cocktail consisting of casirivimab and imdevimab for treating non-hospitalized COVID-19 patients, met its primary and key secondary endpoints, showing that REGEN-COV 1,200 mg administered subcutaneously reduced the risk of symptomatic infections by 81%.
The trial, which was jointly run with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), also showed that REGEN-COV protected household contacts from exposure to SARS-CoV-2 at home, with 72% protection against symptomatic infections in the first week and 93% in subsequent weeks.
Regeneron says it will share data with US Food and Drug Administration and request emergency use authorization expansion to include COVID-19 prevention for appropriate populations using a 1,200-mg subcutaneous dose.
Roche, which is responsible for REGEN-COV outside the US, continues to work with the European Medicines Agency, governments, and other health authorities globally.
Additionally, a second Phase III trial undertaken in collaboration with the NIAID showed that REGEN-COV reduced the overall risk of progressing to symptomatic COVID-19 by 31% (primary endpoint and by 76% after the third day.
Separately, the newly updated NIH COVID-19 Treatment Guidelines strongly recommend that REGEN-COV be used in non-hospitalized COVID-19 patients at high risk of clinical progression.
Inovio Reports Results of COVID-19 Vaccine Against Variants
Inovio, a Plymouth Meeting, Pennsylvania-based biopharmaceutical company developing DNA-based immunotherapies for cancer and infectious diseases, reports that INO-4800, its COVID-19 DNA vaccine candidate, induced neutralizing antibodies and T cell responses against the UK, South African, and Brazilian COVID-19 variant strains.
Collectively, the company said that the studies showed T cell responses in conjunction with neutralizing antibody against both emerging and potential future viral variants.
FDA Accepts Airway Therapeutics’ IND Application for COVID Drug
Airway Therapeutics, a Cincinnati, Ohio-based biopharmaceutical company developing biologics for respiratory and inflammatory diseases, reports the US Food and Drug Administration (FDA) has accepted its investigational new drug (IND) application to develop its recombinant protein, AT-100, as a treatment for COVID-19.
AT-100 is an engineered version of an endogenous protein. The company says it has been shown in preclinical studies to safely reduce inflammation and infection while modulating the immune response across a range of respiratory diseases inside and outside the lung. Additionally, preclinical studies of AT-100 have shown potential to inhibit SARS-CoV-2 replication and promote viral elimination. The company says AT-100 may also reduce secondary infections in severe COVID-19 patients who are mechanically ventilated in intensive care.
Airway will initiate a Phase Ib clinical trial to confirm the feasibility of intratracheal administrations of AT-100 and its beneficial safety and tolerability profile. Airway is using the FDA’s Coronavirus Treatment Acceleration Program that is aimed at evaluating new treatment options for COVID-19.
In March (March 2021), the FDA approved Airway’s first IND application to develop AT-100 as a preventive treatment for the respiratory disease bronchopulmonary dysplasia in very preterm infants. The Phase Ib clinical trial will begin later this month (as reported on April 12, 2021).
Source: Airway Therapeutics
News on COVID-19 testing
FDA Authorizes Thermo Fisher’s Automated System for COVID-19 Test
The US Food and Drug Administration has granted emergency use authorization for the Thermo Fisher Scientific’s Amplitude Solution as an automated system for its COVID-19 test.
The Amplitude Solution is a molecular diagnostic testing system that helps clinical labs expand testing capacity by combining Thermo Fisher’s extraction and real-time PCR instruments with liquid-handling products from Tecan Group, a Männedorf, Switzerland-based company specializing in laboratory automation and liquid handling.
Source: Thermo Fisher Scientific