COVID-19 Vaccine Development
Oxford University’s COVID-19 Vaccine Boosts Immune Response in Pigs
On 23rd June 2020, the Pirbright Institute in collaboration with the University of Oxford announced that two doses of the ChAdOx1 nCoV-19 (AZD1222) vaccine were found to produce a greater antibody response than a single dose in pigs. ChAdOx1 nCoV-19 is a chimpanzee adenovirus vaccine vector comprising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. It has been developed at Oxford University’s Jenner Institute and licensed to AstraZeneca. Phase I human clinical trials of the single dose vaccine have already begun following research that showed that monkeys were protected against lung disease after a single immunisation. It is hoped an effective vaccine could be produced as early as later this year.
Studies carried out at Pirbright were designed to determine whether two doses of the new vaccine in pigs might elicit an even greater immune response and therefore maybe a more effective approach to developing a protective response. The results showed that two doses of the vaccine elicit a significantly greater antibody response in pigs, there was an increase in neutralising antibodies which bind to the virus blocking infection. Two doses of the new vaccine could potentially give significantly more protection in humans than a single dose, and therefore lead to a clinical benefit, but further research in humans is required.
Professor Bryan Charleston, Director of The Pirbright Institute stated: “These results look encouraging that administering two injections with the same vaccine boosts antibody responses that can neutralise the virus, but it is the response in humans that is important. The pig has proved to be a valuable model for testing human vaccines for other diseases to give an indication of the type of immune response induced and testing different doses. Pigs are more physiologically similar to humans than some other animal models, for example their body weight and metabolic rate, and are more accessible than studies using non-human primates.”
GSK and Clover’s COVID-19 Vaccine Moves Into Human Trials
On 19th June 2020, GlaxoSmithKline (GSK) announced initiation of a Phase I study using adjuvanted COVID-19 vaccine result of partnership with Clover Biopharmaceuticals. The study evaluates Clover’s COVID-19 S-Trimer vaccine (SCB-2019) in combination with GSK’s pandemic adjuvant system.
Initiation of the trial follows promising preclinical results which showed the beneficial effect of GSK’s pandemic adjuvant for the SCB-2019 vaccine candidate, with high neutralizing antibody levels elicited in multiple animal species. Preliminary safety and immunogenicity results for the Phase I study are expected in August, while planning for a global Phase IIb/III vaccine efficacy trial has already begun, with initiation scheduled for later this year.
Thomas Breuer, chief medical officer of GSK Vaccines stated: “Our deliberate approach is to combine our proven pandemic adjuvant technology with protein-based COVID-19 vaccine candidates from several collaborators. We believe this holds the promise to produce vaccines at scale, potentially benefiting billions of people”.
PDS Biotechnology and Farmacore Biotechnology Announce Partnership for COVID-19 Vaccine
On 17th June 2020, US-based immunotherapy company PDS Biotechnology and Brazilian biotechnology firm Farmacore Biotechnology announced partnership for co-development of Versamune®-CoV-2FC, a Versamune®-based vaccine aimed at preventing COVID-19 infection. As part of their partnership, Versamune®-CoV-2FC will be developed for Phase I testing in Brazil, the vaccine combines a Farmacore-developed recombinant SARS-CoV-2 protein with PDS Biotech’s Versamune® platform nanotechnology. The vaccine’s target profile is to provide rapid induction of neutralising antibodies, as well as killer T-cells and memory T-cells against the virus, in patients vaccinated with PDS0204 to protect against COVID-19 and to prevent spread of the infection.
Dr. Frank Bedu-Addo, Chief Executive Officer, PDS Biotech stated: “We are excited to expand our ongoing collaboration with Farmacore, which provides an opportunity to rapidly accelerate development of a novel COVID-19 vaccine into Phase I clinical testing in Brazil. We believe that pairing PDS Biotech’s Versamune® T-cell activating vaccine technology with Farmacore’s recombinant SARS-CoV-2 protein will allow us to quickly assess the efficacy of Versamune®-CoV-2FC to potentially reduce the continuing spread of COVID-19 infections.”
European Commission (EC) Launches COVID-19 Vaccine Strategy
On 17th June 2020, the European Commission (EC) unveiled a European strategy focused on fast tracking the development, manufacturing and deployment of COVID-19 vaccines.
The strategy has the following goals:
- Ensuring the quality, safety and efficacy of vaccines;
- Securing swift access to vaccines for Member States and their populations while leading the global solidarity effort;
- Ensuring equitable access to an affordable vaccine as early as possible.
EC President Ursula von der Leyen stated: “This is a moment for science and solidarity. Nothing is certain, but I am confident that we can mobilise the resources to find a vaccine to beat this virus once and for all. We must be ready to manufacture and deploy such a vaccine across Europe and the world. This vaccine will be a breakthrough in the fight against the coronavirus, and a testament to what partners can achieve when we put our minds, research and resources together. The European Union will do all in its power to ensure that all peoples of this world have access to a vaccine, irrespective of where they live.”
Daiichi Sankyo to Develop mRNA COVID-19 Vaccine in Japan
On 12th June 2020, Daiichi Sankyo announced development of a Messenger RNA (mRNA) vaccine against COVID-19 in Japan. The company is taking part of a research project on mRNA vaccine with the title “Development of a Genetic Vaccine for 2019-nCoV” using novel nucleic acid delivery technology.
In a pharmacological evaluation of a prototype mRNA vaccine using animal models, it was observed an increase in antibody titres to the novel coronavirus. Following these results, the company will initiate the development of the mRNA vaccine as a priority project and start to consider an increase in scale toward establishing a supply system. At the same time, it aims to go ahead with clinical studies around March 2021.
COVID-19 Research and Therapeutic Development
FDA Grants Fast Track Status to RLF-100 (Aviptadil) for the Treatment of Respiratory Distress in COVID-19
On 24th June 2020, NeuroRx in partnership with Relief Therapeutics, announced that the Food and Drug Administration (FDA) granted Fast Track Designation to NeuroRx for the investigation of RLF-100 (Aviptadil) for the treatment of acute lung injury/acute respiratory distress syndrome associated with COVID-19. RLF-100 is a synthetic form of human Vasoactive Intestinal Peptide (VIP) which reduces inflammation in the lungs and protects the alveolar type II cells that are believed to be an entry route for the SARS-CoV-2 to invade the lungs.
Prof. Jonathan Javitt, MD, MPH, CEO and Chairman of NeuroRx stated: ““We at NeuroRx are enormously appreciative of the FDA’s commitment to accelerating the development of any potential treatment for COVID-19. We hope to live up to the trust that has been placed in us by bringing a potentially life-saving treatment to patients.”
Novartis Discontinues Hydroxychloroquine Clinical Trial
On 19th June 2020, Novartis announced decision to discontinue its sponsored hydroxychloroquine clinical trial for COVID-19 due to acute enrolment challenges that have made trial completion infeasible. The trial recruitment challenges made it unlikely that the clinical team will be able to collect meaningful data in a reasonable timeframe to determine the effectiveness of the drug in treating patients with the virus. No safety issues have been reported, and there are no conclusions on efficacy from the study.
The company will continue to supply hydroxychloroquine for ongoing investigator-initiated trials and upon government requests, as appropriate, where certain conditions are met, and the medicine is used in accordance with a nationally endorsed treatment protocol. Novartis continues to monitor ongoing guidance from health authorities on the further study of hydroxychloroquine for COVID-19, as well as the decision by the FDA to stop the emergency use authorisation of the drug for COVID-19 treatment. Ongoing studies involving other Novartis treatments continue, as well as the newly announced support of a potential vaccine.
UK Government Approves Dexamethasone for Treatment of COVID-19 Patients
On 16th June 2020, the UK Government authorised the immediate use of anti-inflammatory drug dexamethasone for the treatment of COVID-19 on the National Health Service (NHS), following positive data from the RECOVERY trial.
Oxford University’s RECOVERY trial was funded by the UK government via the National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI). Data from the trial showed that dexamethasone significantly reduced the risk of death in COVID-19 patients on ventilation by as much as 35% and patients on oxygen by 20%, reducing the total 28-day mortality rate by 17%. Hospitalised patients requiring oxygen, including those on ventilators, across the UK will now be able to be treated using dexamethasone.
Health Secretary Matt Hancock stated: “I’m absolutely delighted that today we can announce the world’s first successful clinical trial for a treatment for COVID-19. This astounding breakthrough is testament to the incredible work being done by our scientists behind the scenes. From today the standard treatment for COVID-19 will include dexamethasone, helping save thousands of lives while we deal with this terrible virus.”
Calquence ® Shows Positive Result in Hospitalised COVID-19 Patients
On 5th June 2020, AstraZeneca(AZ) announced that results published in Science Immunology showed that Calquence® (acalabrutinib), a Bruton’s tyrosine kinase (BTK) inhibitor, reduced markers of inflammation and improved clinical outcomes of patients with severe COVID-19. Study involved peer reviewed case series of 19 hospitalised patients with COVID-19 disease and severe hypoxia and/or inflammation as a collaboration from investigators across the US, including AZ’s scientists, and led by Wyndham Wilson, M.D., Ph.D. and Louis Staudt, M.D., Ph.D. at the National Cancer Institute of the National Institutes of Health in the US.
The publication describes the effects of Calquence® administration in patients with severe respiratory illness caused by COVID-19. A virus-induced hyperimmune response or “cytokine storm” is hypothesised to be a major pathogenic mechanism of respiratory illness in these patients, and evidence suggests that dysregulated BTK-dependent lung macrophage signalling mediates this cytokine storm and plays a role in COVID-19 pneumonia.
José Baselga, Executive Vice President, Oncology R&D, stated: “The science supporting investigation of the use of Calquence in patients with severe COVID-19 is strong. The encouraging preliminary data in this case series has informed the initiation of global phase II trials, notably the CALAVI programme. We look forward to completing recruitment and obtaining data in these trials as soon as possible to further our understanding of what this potential treatment could mean for patients.”
FDA and E.C. approvals
FDA Approves First Treatment for Adult Onset Still’s Disease
On 16th June 2020, the FDA announced approval of Ilaris (canakinumab) to Novartis, an injection for the treatment of Active Still’s disease, including Adult-Onset Still’s Disease (AOSD). AOSD is a rare and serious autoinflammatory disease of unknown origin. Ilaris works by blocking the effects of interleukin-1 (IL-1) and suppressing inflammation in patients with this autoinflammatory disorder. The safety and efficacy of Ilaris for the treatment of patients with AOSD was established using comparable pharmacokinetic exposure and extrapolation data of established efficacy of canakinumab in patients with Systemic Juvenile Idiopathic Arthritis (SJIA), as well as the safety of canakinumab in patients with AOSD and other diseases. Ilaris was previously approved for SJIA in patients aged 2 years and older. Ilaris was granted Priority Review designation, under which the FDA’s goal is to take action on an application within six months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.
Nikolay Nikolov, M.D., acting director of the Division of Rheumatology and Transplant Medicine in the FDA’s Center for Drug Evaluation and Research stated:“ Prior to today’s approval, patients had no FDA-approved treatments for their disease, which can include symptoms such as painful arthritis, fevers and rash. Today’s approval provides patients with a treatment option.”
FDA Revokes Emergency Use Authorisation for Chloroquine and Hydroxychloroquine
On 15th June 2020, the FDA announced that it had revoked the emergency use authorization (EUA) that allowed for chloroquine phosphate and hydroxychloroquine sulphate to be used to treat certain hospitalised patients with COVID-19 when a clinical trial was unavailable, or participation in a clinical trial was not feasible. The agency determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorised uses in the EUA and following ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits no longer outweigh the known and potential risks for the authorised use.
Patrizia Cavazzoni, M.D., acting director of the FDA’s Center for Drug Evaluation stated: “While additional clinical trials continue to evaluate the potential benefit of these drugs in treating or preventing COVID-19, we determined the emergency use authorization was no longer appropriate. This action was taken following a rigorous assessment by scientists in our Center for Drug Evaluation and Research. We remain committed to using every tool at our disposal in collaboration with innovators and researchers to provide sick patients timely access to appropriate new therapies. Our decisions will always be based on objective and rigorous evaluation of the scientific data. This will never change.”
Sanofi’s Receives EC Approval of Sarclisa® for Adults With Multiple Myeloma
On 3rd June 2020, Sanofi’s announced that the European Commission (EC) approved Sarclisa® (isatuximab) in combination with pomalidomide and dexamethasone (pom-dex) for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy. Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor. CD38 is highly and uniformly expressed on MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa. It is designed to induce apoptosis and immunomodulatory activity.
John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi stated: “The EC approval of Sarclisa represents an important additional therapeutic option and may set a new standard of care for myeloma patients in Europe who are in need of new effective treatments because their disease has returned or they have become refractory to their previous treatment. Sarclisa in combination with pom-dex demonstrated median progression-free survival of nearly one year, a five-month improvement over pom-dex alone, in patients who had already failed at least two prior therapies.”
Issue Number: PN2006
Would you like a personal copy directly to your mailbox each month? Just send an email to email@example.com with the subject “Pharma News Please”