COVID-19 Vaccine Development

MHRA Initiates Rolling Review of Moderna’s mRNA Vaccine Against COVID-19

On 27th October 2020, Moderna, a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has started the rolling review process of mRNA-1273, their vaccine candidate against COVID-19. This action follows up on positive results from a preclinical viral challenge study of mRNA-1273 and the positive interim analysis of the Phase I study of mRNA-1273 in adults published in the New England Journal of Medicine.

The company has initiated the rolling submission of mRNA-1273 data for review, in consideration of a potential authorisation by the MHRA, provided the vaccine candidate meets the regulatory agency’s standards of safety, effectiveness, and quality. The Phase I interim analysis showed that mRNA-1273 was well-tolerated across all age groups and induced rapid and strong immune responses against SARS-CoV-2. The vaccine candidate is currently being studied in a Phase III randomised, placebo-controlled trial of 30.000 participants in the US.

Stéphane Bancel, Chief Executive Officer of Moderna  stated: “We appreciate the collaboration we have had to date with regulatory authorities around the world, and the process established by the MHRA to address this ongoing public health emergency. This is a great example of what’s being done to support efforts to deliver a safe and effective vaccine to UK citizens as safely and efficiently as possible.”

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AstraZeneca Receives FDA Authorisation to Restart COVID-19 AZD1222 Vaccine US Phase III Trial

On 23rd October 2020, AstraZeneca announced that the US Food and Drug Administration (FDA) has authorised the restart of Phase III clinical trial of AstraZeneca and Oxford University’s COVID-19 vaccine candidate, AZD1222 in the US following the resumption of trials in other countries in recent weeks. As part of the review process for trial safety events, a voluntary pause to vaccination across all global trials was triggered on 6th September 2020 to allow the examination of safety data by independent monitoring committees. The recommendations from these reviews have been supported by international regulators, who also confirmed that the trials were safe to resume.

Pascal Soriot, AstraZeneca’s Chief Executive Officer, stated: “The restart of clinical trials across the world is great news as it allows us to continue our efforts to develop this vaccine to help defeat this terrible pandemic. We should be reassured by the care taken by independent regulators to protect the public and ensure the vaccine is safe before it is approved for use.”

Results from the late-stage trials are anticipated for later this year, depending on the rate of infection within the communities where the clinical trials are being conducted. AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech and uses a replication-deficient chimpanzee viral vector based on a weakened version of an adenovirus that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein.

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ImmunityBio and NantKwest Announce First Patient Dosed in Phase I Clinical Trial of COVID-19 Vaccine Candidate hAd5

On 21st October 2020, ImunityBio, a privately-held immunotherapy company, and NantKwest, a clinical-stage natural killer cell-based therapeutics company, announced that the first patient had been dosed in the Phase I clinical trial of hAd5-COVID-19, a COVID-19 vaccine candidate that targets the inner nucleocapsid (N) and the outer spike (S) protein, engineered to activate both T cells and antibodies against the coronavirus (SARS-CoV-2).

The Phase I trial, which is being conducted at the Hoag Hospital in Newport Beach, California, is currently enrolling healthy adult subjects up to age 55 with the aim of accessing the safety and reactogenicity of two doses of the vaccine candidate. Ad5-COVID-19 will be administered as both a prime and boost using the same vector platform to enable sustained protection against SAR-CoV-2. The trial’s main goal is to examine the safety and reactogenicity of two doses of the vaccine. The companies are also pursuing development for oral, inhalational, and intranasal administration of hAd5.

Dr. Patrick Soon-Shiong, Chairman and CEO of ImmunityBio and NantKwest stated: “Our vaccine candidate, hdA5-COVID-19, targets both the nucleocapsid protein on the interior of the virus particle and the spike protein on the virus’ surface. We believe this dual targeting is a key advantage that may lead to the stimulation of both T-cell-mediated and antibody-mediated immunity to SARS-CoV-2, which is an important differentiator from other vaccine candidates that only target the spike protein.”

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Russia’s Chumakov Center Initiates Covid-19 Vaccine Candidate Trials

On 19th October 2020, Russia’s Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products has launched clinical trials of its vaccine in St. Petersburg with the participation of 30 volunteers, the trials are set to end by late 2020.

On October 6th, clinical trials of a whole-virion inactivated vaccine developed by the Chumakov Center began in Novosibirsk. Whole-virion vaccines are based on artificially weakened viruses unable to cause a disease also known as inactivated viruses. The Volunteers aged 18 to 45 taking part in the research have previously undergone screening tests and medical examination prior to vaccination. All volunteers tested negative for COVID-19 and had no antibodies to the virus before the trials.

Another Russian COVID-19 vaccine, EpiVacCorona developed by the State Research Center of Virology and Biotechnology “Vector,” was registered on October 14, with post-registration trials set to begin shortly.

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Johnson & Johnson Receives European Commission Approval of Agreement to Supply Doses of Janssen’s COVID-19 Vaccine Candidate

On 8th October 2020, Johnson & Johnson (J&J) announced that the European Commission (EC), acting on behalf of the European Union (EU) Member States, has approved an Advance Purchase Agreement in which the Janssen Pharmaceutical Companies will supply 200 million doses of its COVID-19 vaccine candidate to EU Member States following approval or authorisation from regulators. The EU Member States also have the option to secure up to 200 million additional doses.

Paul Stoffels, Vice Chairman of the Executive Committee and Chief Scientific Officer, Johnson & Johnson stated: “The COVID-19 pandemic continues to threaten communities worldwide and we have a responsibility to ensure access to our COVID-19 vaccine as soon as we can. We appreciate the Commission’s and the Member States’ support for our COVID-19 vaccine candidate and development efforts”.

J&J has also announced plans to allocate up to 500 million vaccine doses toward international efforts to ensure access for lower income countries, with delivery beginning mid next year following approval or authorisation from regulatory authorities.

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EMA Initiates Review of BNT162b2 COVID-19 Vaccine

On 6th October 2020 the European Medicines Agency (EMA) announced review of data from COVID-19 vaccine BNT162b2, which is being developed by BioNTech in partnership with Pfizer. EMA’s human medicines committee (CHMP) has started evaluating the first batch of non-clinical data on the vaccine, which comes from laboratory studies, the decision to start the rolling review of BNT162b2 is based on preliminary results which suggested that the vaccine triggers the production of antibodies and T cells that target the virus.

It is expected that when an individual is vaccinated with BNT162b2 , their cells will read the genetic instructions and produce SARS-CoV-2’ spike protein, their immune system will then treat this protein as foreign and produce antibodies and T cells against it. If, later on, the vaccinated individual comes into contact with SARS-CoV-2, the immune system will recognise the virus and be prepared to attack it and prevent its entry into the body’s cells and destroy infected cells, thus helping to protect against COVID-19.

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COVID-19 Research and Therapeutic Development

Italian Medicines Agency Greenlights Trial for the Use of Raloxifene for COVID-19 Treatment

On 27th October 2020, Italian Medicines Agency (AIFA) granted approval to conduct human clinical trials on raloxifene, a generic osteoporosis drug to treat patients with mild COVID-19 symptoms.  The clinical study will assess the safety and efficiency of raloxifene in blocking the replication of the virus in cells, and thus hold up the progression of the disease.

The trial will take place at the National Institute for Infectious Diseases in Rome and will also involve the Humanitas Research Hospital in Milan. In the initial phase, up to 450 participants in three separate treatment groups will be administered a 7-day treatment of raloxifene capsules in a randomised sample.

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ANA Therapeutics Initiates Clinical Trial of Oral Niclosamide Formulation for COVID-19 Treatment

On 26th October 2020, Biotech company ANA Therapeutics announced initiation of Phase II/III trial to access the safety and efficacy of its oral niclosamide (ANA001) formulation for treating patients with moderate COVID-19. The trial is the first of its kind to be initiated in the US for testing COVID-19 treatment with niclosamide, a drug use to treat tapeworm infections.

Nadja Mannowetz, ANA’s Chief Scientific Officer stated: “There is a great need for additional therapeutic options to reduce the impact of COVID-19 on patients. Niclosamide has demonstrated antiviral as well as immune-modulating activities in preclinical studies. This trial provides the first opportunity to evaluate its safety and potential to improve clinical outcomes and reduce hospital stay by reducing viral load, inflammation linked to cytokine dysregulation, acute respiratory distress syndrome, and disease related blood coagulation.”

The trial is a randomised, placebo-controlled study that will be conducted in two parts at a total of 20 clinical sites in the US. In both study parts, hospitalised patients with moderate COVID-19 will be administered a seven-day course of niclosamide capsules in addition to standard of care. The primary objective is safety and tolerability, and secondary objectives include measurement of efficacy and pharmacokinetics. The second part of the trial will enrol several hundred patients, with the primary objectives being efficacy, safety and tolerability. Secondary goals relate to clinical improvement and the need and duration for rescue therapy.

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FDA Approves Gilead’s Remdesivir for Coronavirus Treatment

On 22nd October 2020, the FDA announced approval of antiviral drug Veklury (remdesivir) for use in adult and paediatric patients aged 12 years of age and older and weighing at least 40 kilograms for the treatment of COVID-19 requiring hospitalisation. Earlier in May, the FDA had granted the drug an emergency use authorisation (EUA), allowing hospitals and doctors to use it on patients hospitalised with the disease even though it had not been formally approved by the agency.

FDA’s Commissioner Stephen M. Hahn stated: “The FDA is committed to expediting the development and availability of COVID-19 treatments during this unprecedented public health emergency. Today’s approval is supported by data from multiple clinical trials that the agency has rigorously assessed and represents an important scientific milestone in the COVID-19 pandemic. As part of the FDA’s Coronavirus Treatment Acceleration Program, the agency will continue to help move new medical products to patients as soon as possible, while at the same time determining whether they are effective and if their benefits outweigh their risks.”

The approval of Veklury was supported by the FDA’s review of data from three randomised, clinical trials that included patients hospitalised with mild-to-severe COVID-19, the agency granted approval and reissued the revised EUA to Gilead Sciences Inc.

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Open Orphan Subsidiary hVivo Signs Deal with UK Government for Covid-19 Challenge Study

On 20th October 2020, it was announced that UK Government had signed a contract with Open Orphan subsidiary hVIVO for the development of a COVID-19 human challenge study model, involving healthy volunteers being deliberately exposed to the virus in controlled settings. hVivo will undertake the project, which involves the manufacture of the challenge virus and the first-in-human characterisation study.

The study will be sponsored by Imperial College London and conducted by hVivo at the Royal Free Hospital’s specialist research unit in London, and hVivo will expand its clinical operations in London to facilitate the work. According to the company the UK government has secured the first three slots to test vaccines using hVivo’s Covid-19 challenge study, which is expected to start in 2021.

Open Orphan executive chairman Cathal Friel stated: “At Open Orphan we are pleased to be working on behalf of the UK government and in partnership with two great institutions, Imperial College London and the Royal Free Hospital. We look forward to working with our partners to develop a Covid-19 human challenge study model which will be used to safely accelerate the discovery of effective vaccines and antivirals against Covid-19.”

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 Eli Lilly Pauses COVID-19 Antibody Trial due to Safety Concerns

On 14th  October 2020, Eli Lilly’s phase III trial of a leading COVID-19 candidate treatment had been announced to have been  put on hold for safety reasons after five days of treatment, and a week after its maker applied for an EUA.

The Activ-3 trial is studying 326 subjects hospitalised with mild to moderate COVID-19. It has a two-stage format, with 700 more subjects being recruited if the early stages go well, however all recruitment as well as treatment is now on hold. Another Phase III trial, Activ-2, is studying the same antibody in patients with mild to moderate COVID-19 who are not hospitalised. It is unaffected by the pause.

The interruption was called out of caution by the trial’s data and safety monitoring board (DSMB), an independent group of experts. The trial remains blinded, so neither the treating physicians nor Eli Lilly know which patients were receiving treatment and which placebo. The board will review the data and make a recommendation on whether to resume activities.

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Other Pharma Industry News

Novartis Receives Orphan Drug Designation for Branaplam (LMI070) in Huntington’s disease (HD)

On 21st October 2020, Novartis announced that the FDA granted Orphan Drug Designation for Branaplam (LMI070) in Huntington’s disease (HD). Branaplam is a small molecule RNA splicing modulator, administered orally, once weekly, it is currently in the investigational stage for the treatment of spinal muscular atrophy (SMA).

Huntington’s disease is an inherited neurodegenerative disease that leads to progressive disability and death, people suffering from the disease have mutated huntingtin (HTT) gene. Pre-clinical data showed that Branaplam reduced levels of the mutant huntingtin protein, during the investigation of Branaplam in SMA, it reduced huntingtin messenger RNA (mRNA) in SMA patients.

At the moment treatment options for Huntington’s disease are limited to symptomatic treatments, and there are no approved disease-modifying therapies available that can delay disease onset or slow disease progression. Based on pre-clinical data findings Novartis intends to start a development program for Branaplam to determine if it has the potential to be a transformative treatment for people with this condition. Novartis plans to initiate a Phase IIb trial for Branaplam in HD patients in 2021.

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Takeda and Arrowhead Collaborate to Co-Develop and Co-Commercialize ARO-AAT for Alpha-1 Antitrypsin-Associated Liver Disease

On 8th October 2020, Takeda Pharmaceutical and Arrowhead Pharmaceuticals announced a partnership and licensing agreement to develop ARO-AAT, a Phase II investigational RNA interference (RNAi) therapy to treat alpha-1 antitrypsin-associated liver disease (AATLD). ARO-AAT is a potential first-in-class therapy designed to reduce the production of mutant alpha-1 antitrypsin protein, the cause of AATLD progression.

Under the agreement, Takeda and Arrowhead will co-develop ARO-AAT which, if approved, will be co-commercialized in the US under a 50/50 profit-sharing structure. Outside the US, Takeda will lead the global commercialisation strategy and receive an exclusive license to commercialise.

Asit Parikh, Head Gastroenterology Therapeutic Area Unit at Takeda stated: “AAT-associated liver disease is a devastating condition for which there are no approved therapies. With its RNAi-based mechanism of action, ARO-AAT has the potential to treat the underlying cause of AATLD, thereby helping patients avoid the need for liver transplantation and associated co-morbidities. We are excited to collaborate with Arrowhead to bring forward this exciting late-stage liver asset for the Alpha-1 community as part of our growing GI portfolio.”

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Issue Number: PN2010

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