In the pipeline: What the next wave of COVID-19 vaccines could look like
Vaccines from big names such as Pfizer/BioNTech, Moderna, AstraZeneca and Johnson & Johnson continue to scale up production and distribution. But there are still 112 COVID-19 vaccine candidates in clinical development and 184 in pre-clinical development, according to the WHO’s vaccine tracker.
These range from technologies such as mRNA and non-replicating viral vectors to DNA and live attenuated virus vaccines – as well as those that seek to find an alternative to needle administration.
We take a look at some of the candidates coming through the pipeline; the point of difference they hope to offer from approved and authorized vaccines; and their timeline for development.
Valneva’s inactivated candidate: VLA2001
Valneva announced this month that it has commenced rolling submission for authorization of its COVID-19 vaccine candidate, VLA2001, in the UK.
VLA2001 is currently being studied in the UK in a pivotal Phase 3 trial, Cov-Compare (VLA2001-301), for which topline results are currently expected early in the fourth quarter of 2021.
Valneva champions a ‘tried and tested’ approach with its inactivated candidate. The vaccine is expected to conform with standard cold chain requirements of 2 degrees to 8 degrees celcius.
The manufacturing process for VLA2001 is already at final industrial scale and the company commenced commercial production in January 2021 to optimize the timeline for potential deliveries of the vaccine. The UK government has ordered 100 million doses for supply in 2021 and 2022, with the option to purchase a further 90 million doses through 2025.
Valneva believes UK regulatory approval could come by the end of the year.
Akston Biosciences: AKS-452
Akston Biosciences has taken its second-generation protein subunit COVID-19 vaccine candidate, AKS-452, into a Phase 1/2 trial this month.
The Phase I trial showed AKS-452 to be safe and well-tolerated; with the candidate producing a 100% seroconversion rate in the 90 microgram single-dose regimen, as well as in the 45 microgram two-dose regimen.
The AKS-452 has been shown to be shelf stable for at least six months at 25° Celsius (77° Fahrenheit) and maintains its potency for one month at 37° Celsius (99° Fahrenheit): making it idea for distribution in countries with limited infrastructure.
Phase 2 readouts are expected in Q3 2021.
CureVac and GSK: CV2CoV
CureVac and GSK’s second-generation mRNA COVID-19 vaccine candidate has demonstrated improved immune responses and protection over the first-generation candidate, according to results from a preclinical study published this month.
CV2CoV was engineered with specifically optimized non-coding regions to exhibit improved mRNA translation for increased and extended protein expression compared the first-generation mRNA backbone.
In an animal model, CV2CoV was shown to induce broad antibody and cellular immune responses very similar to the breadth of the immune responses observed after infection with SARS-CoV-2, according to the companies.
Immune responses were found against the original SARS-CoV-2 virus as well as the Beta and Delta Variants of Concern and the Lambda Variant of Interest.
A Phase 1 clinical trial on CV2CoV is expected to start in Q4 2021.
Arcturus Therapeutics: ARCT-021 and ARCT-154
San Diego’s Arcturus, a clinical stage mRNA company focusing on infectious disease vaccines liver and respiratory rare diseases, is developing two COVID-19 candidates in parallel: ARCT-021 (its lead candidate) and ARCT-154 (targeting variants of concern, including the Delta variant). The vaccines have been created using Arcturus’ STARR mRNA technology.
Arcturus’ lead mRNA COVID-19 vaccine candidate, ARCT-021, is currently in a Phase 2 study in the US and Singapore, with data on expected in H2 2021.
Meanwhile, its manufacturing partner in Vietnam, Vinbiocare, this month received approval for a Clinical Trial Application (CTA) from the Vietnam Ministry of Health to advance the variant-focused ARCT-154 into a Phase 1/2/3 study. The randomized, observer-blind, placebo-controlled design is sponsored and funded by Vinbiocare (a subsidiary of Vingroup, the largest private industry conglomerate in the country).
Preclinical research suggests that non-human primate immunization with ARCT-154 elicits neutralizing antibodies to SARS-CoV-2 variants of concern, including the Delta variant (protection was highest against Alpha, followed by Delta then Gamma then Beta).
If the clinical trial proves successful at interim evaluations, Emergency Use Approval (EUA) by the Vietnam Ministry of Health is anticipated by the end of the year.
NVX-CoV2373 is a protein-based vaccine candidate engineered from the genetic sequence of the first strain of SARS-CoV-2. It was created using Novavax' recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is formulated with Novavax' saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies.
NVX-CoV2373 is being evaluated in two pivotal Phase 3 trials: a trial in the UK that demonstrated efficacy of 96.4% against the original virus strain, 86.3% against the Alpha (B.1.1.7) variant and 89.7% efficacy overall; and the PREVENT-19 trial in the US and Mexico that demonstrated 100% protection against moderate and severe disease and 90.4% efficacy overall.
It is also being tested in two ongoing Phase 2 studies that began in August 2020: a Phase 2b trial in South Africa that demonstrated 55% efficacy overall in HIV-negative participants and 48.6% efficacy against a newly emerging escape variant first described in South Africa, and a Phase 1/2 continuation in the US and Australia.
Novavax is working to complete rolling submission for authorization to the European Medicines Agency (EMA) in the third quarter of 2021. Novavax and Serum Institute of India have together applied for Emergency Use Authorization in India, Indonesia and the Philippines.
NVX-CoV2373 is stored and stable at 2° to 8°C, allowing the use of existing vaccine supply chain channels for its distribution.
Sanofi, GSK and Translate Bio
Sanofi and GSK started a Phase 3 clinical study for an adjuvanted recombinant protein COVID-19 vaccine candidate in May. A two stage design is evaluating vaccine formulations against both the original D.614 virus as well as B.1.351. Its timetable suggests that - pending positive Phase 3 outcomes and regulatory reviews - the vaccine could be approved / authorized in Q4 2021.
Sanofi is also working to develop a second COVID-19 mRNA vaccine based on its work with Translate Bio – which it acquired this month - with Phase 1/2 study with results expected in Q3 2021.
Scancell: SCOV1 and SCOV2
Scancell is assessing the safety and immunogenicity of the two vaccine candidates, SCOV1 and SCOV2, evaluating different vaccine doses delivered by two alterative injection routes using needle-free systems. It has chosen PharmaJet Needle-free Injection Systems to either administer the vaccine via intradermal injection with the PharmaJet Tropis Needle-free Injection System; or via intramuscular delivery with the PharmaJet Stratis system.
Needle-free injectors use a narrow stream of fluid to penetrate the skin, delivering vaccines and other pharmaceuticals to the required tissue depth. Both the PharmaJet systems have been clinically proven with a wide range of vaccines, including the delivery of DNA products. According to the company, the injection systems are easy to use, eliminate needlestick injuries and have the potential to expand vaccine coverage to subjects with a fear of needles.
Scancell’s preclinical studies have confirmed that PharmaJet delivery of its vaccines induces potent immune responses against both S and N antigens (meanwhile, PharmaJet’s tech is being used with Zydus Cadila’s plasmid DNA vaccine, which has just received EUA from the Drug Controller General of India).
The vaccine candidates are due to enter a Phase 1 trial in South Africa in H2, 2021. Once safety data has been received, a trial in the UK will administer the vaccine as a booster shot to people already fully vaccinated with two authorized COVID-19 vaccines.
In addition to evaluating the virus-neutralising antibodies, Scancell will also analyse the T cell responses to the N protein in the trials, which will provide additional information and data on the potential utility of both SCOV1 and SCOV2 against future SARS-CoV-2 variants.