Candidate: NVX-CoV2373 (Nuvaxovid™ in Europe; COVOVAX™ in India and the Philippines); TAK-019 in Japan

Category: VAX

Type: Stable, prefusion protein made using Novavax’ proprietary nanoparticle technology, and incorporating its proprietary saponin-based Matrix-M™ adjuvant.

2022 Status: Canada Authorizes Nuvaxovid—Novavax said February 17 that Health Canada has granted authorization for Nuvaxovid™ for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older.

Clinical trial data submitted to Health Canada for review included two pivotal Phase III clinical trials: PREVENT-19 (NCT04611802), which enrolled approximately 30,000 participants in the U.S. and Mexico and published results in the The New England Journal of Medicine (NEJM); and a trial with almost 15,000 participants in the U.K. which was also published in NEJM (EudraCT number, 2020-004123-16).

Novavax and the Government of Canada signed an advance purchase agreement in January for 52 million doses of the vaccine, with the option for up to an additional 24 million doses, and established a memorandum of understanding to produce the vaccine at the National Research Council of Canada’s (NRC) Biologics Manufacturing Centre in Montréal in February 2021.

Singapore Interim Authorization—Novavax said February 14 that the Singapore Health Sciences Authority (HSA) has issued interim authorization for Nuvaxovid COVID-19 Vaccine (recombinant, adjuvanted) for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older.

Clinical trial data submitted to HSA for review included two pivotal Phase III clinical trials: PREVENT-19 (NCT04611802), which enrolled approximately 30,000 participants in the U.S. and Mexico and published results in the The New England Journal of Medicine (NEJM); and a trial with almost 15,000 participants in the U.K. which was also published in NEJM (EudraCT number, 2020-004123-16).

EUA REQUEST SUBMITTED TO FDA: Novavax said January 31 that it submitted a request to the FDA for Emergency Use Authorization (EUA) of NVX-CoV2373 for immunization of individuals 18 year of age and older against SARS-CoV-2.

The submission is supported by data that included results of two pivotal trials showing an overall efficacy of approximately 90% and a positive safety profile. The two trials were PREVENT-19 (NCT04611802), which enrolled approximately 30,000 participants in the U.S. and Mexico and on December 15, 2021, published results in The New England Journal of Medicine (NEJM); and a trial with almost 15,000 participants in the U.K. which was also published in NEJM on September 23, 2021 (EudraCT number, 2020-004123-16). As part of PREVENT-19, a booster study is ongoing to evaluate the safety and effectiveness of a third does of the vaccine, as well as a study in adolescents aged 12-17.

Australian Provisional Approval—Australia’s Therapeutic Goods Administration (TGA) has granted approval for provisional registration of NVX-CoV2373, Novavax said January 19. The vaccine—the first protein-based COVID-19 vaccine authorized for use in Australia—will be supplied under the brand name Nuvaxovid™.

According to the company, a booster trial for Nuvaxovid and a Phase I/II trial for a combination seasonal influenza and COVID-19 vaccine are currently underway in Australia. Overall, nearly 1,500 Australians have participated in Novavax COVID-19 and combination vaccine clinical trials.

2021 Status: Final Data Package Submitted—Novavax said December 31 that it submitted its final data package, including a complete chemistry, manufacturing and controls (CMC) module, to fulfill the prerequisites for its emergency use authorization (EUA) application request to the FDA for NVX-CoV2373. The company said it expected to submit its EUA request for the vaccine in one month, and later supplement the submission with data from additional manufacturing sites across Novavax’ global supply chain.

Positive Initial Data vs. Omicron—Novavax on December 22 said that NVX-CoV2373 showed broad cross-reactivity against Omicron (B.1.1.529) and other circulating variants from a primary two-dose regimen, with responses that increased following a third dose at six months, according to data that the company said would be posted on a preprint and submitted for peer review in the future.

ACE2-inhibition titers increased beteen six-fold (vs. the initial strain of SARS-CoV-2) to 19.9-fold (vs. Omicron) compared to peak responses following the two-dose primary series. Those results represented a 54.4-fold (prototype), a 24.4-fold (Delta) and a 36.3-fold (Omicron) increase from before the booster, Novavax said.

Anti-spike IgG titers after Dose 3 increased 5.4-fold (vs. initial SARS-CoV-2) to 9.3-fold (vs. Omicron) from peak responses seen after the two-dose primary vaccination.The results represented a 61.1-fold jump vs SARS-CoV-2 and a 73.5-fold increase vs. Omicron compared with before the Dose 3 boost, Novavax said.

As part of an ongoing study, a single booster dose of 5 µg SARS-CoV-2 rS with 50 µg Matrix-M™ adjuvant was administered to healthy adult participants approximately six months after their primary two-dose vaccination series. Immune responses against SARS-CoV-2 were assessed twenty-eight days following the booster dose.

WHO GRANTS EUL—The World Health Organization has granted its Emergency Use Listing (EUL) for NVX-CoV2373, Novavax and the Serum Institute of India (SII) said December 17—the ninth COVID-19 vaccine granted EUL status, and the first granted by WHO for a protein-based COVID-19 vaccine. The EUL applies to the version of the vaccine manufactured and marketed by SII as COVOVAX™, a novel recombinant, adjuvanted SARS-CoV-2 rS Vaccine, in India and licensed territories.

An additional EUL filing is under review by the WHO for the Novavax-marketed version, under the brand name Nuvaxovid™.

EMA Reviews Conditional Authorization Application—The European Medicines Agency (EMA) has begun reviewing a conditional marketing authorization application for Novavax’s COVID-19 vaccine, to be marketed in Europe as Nuvaxovid™. The assessment will proceed under an accelerated timeline, according to the EMA.

The agency also said it has already reviewed a “substantial portion” of Novavax’s data on the vaccine during a rolling review. During this phase, EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed non-clinical data from laboratory studies, “some” information on the quality of the vaccine and how it will be produced, and data on its safety, immunogenicity and efficacy against COVID-19 from clinical studies in adults.

Takeda Submits Japan Approval Application—Novavax said December 15 that its partner in Japan, Tajeda Pharmaceutical, submitted a New Drug Application (NDA) to the Ministry of Health, Labour and Welfare (MHLW) in Japan for the COVID-19 vaccine, to be marketed in Japan as TAK-019. The vaccine is the first protein-based COVID-19 vaccine to be submitted under an NDA in Japan.

The NDA submission included an interim analysis from Takeda’s ongoing Phase I/II immunogenicity and safety clinical trial of NVX-CoV2373/TAK-019 in Japan, where the vaccine showed a robust immune response and was well tolerated with no serious adverse events.

Novavax said the companies are working to establish the capability to manufacture TAK-019 at Takeda’s facilities in Japan, and plan to begin distribution in early 2022, pending regulatory approval.

Philippines Grants EUA—The Philippine Food and Drug Administration (FDA) granted emergency use authorization (EUA) to Novavax and partner Serum Institute of India (SII) for NVX-CoV2373, Novavax and SII said November 17. The vaccine will be manufactured and marketed in the Philippines by SII under the brand name COVOVAX™.

As of November 17, NVX-CoV2373 had received EUA in Indonesia, while the companies had also filed for emergency authorization in India and for Emergency Use Listing (EUL) with the World Health Organization (WHO). Novavax has also submitted regulatory filings for its vaccine in the U.K. Australia, New Zealand, Canada, and completed submission of all data and modules in the European Union to support the final regulatory review of its dossier by the European Medicines Agency.

In the U.S., Novavax said it expected to submit the complete package to the FDA by the end of 2021.

South Korean BLA Submitted—Novavax and South Korean partner and SK bioscience said November 15 that they submitted a Biologics License Application (BLA) for NVX-CoV2373 to South Korea’s Ministry of Food and Drug Safety (MFDS)—the first BLA submission for full approval of the Novavax-developed COVID-19 vaccine anywhere in the world, said Stanley C. Erck, the company’s President and CEO.

Novavax and SK bioscience have an existing manufacturing and licensing collaboration that is intended to provide broad and equitable access to NVX-CoV2373 both in South Korea and globally through the COVAX Facility. SK bioscience finalized an advance purchase agreement of undisclosed value with the South Korean government to supply 40 million doses of NVX-CoV2373 to South Korea earlier this year.

Indonesia grants EUA—Indonesia’s National Agency of Drug and Food Control of the Republic of Indonesia, or Badan Peng was Obat dan Makanan (Badan POM), has granted emergency use authorization (EUA) for the Novavax COVID-19 vaccine, which will be marketed by Serum Institute of India (SII) under the name COVOVAX™. The EUA marks the first regulatory authorization for the vaccine, as well as the first regulatory authorization worldwide of a protein-based COVID-19 vaccine based on Phase III clinical data demonstrating efficacy and a favorable safety profile, Novavax said.

“This is a landmark moment for Novavax and our partner, Serum Institute of India, and it is the first of many authorizations that Novavax expects in the coming weeks and months for our vaccine globally,” said Stanley C. Erck, President and Chief Executive Officer, Novavax.

$372M Mabion Manufacturing Agreement—Mabion said October 8 that it signed a $372 million contract manufacturing agreement with Novavax for the large-scale production of the protein antigen used in NVX-CoV2373. The four-year deal is designed to provide production capacity at Mabion’s cGMP facility in Poland through 2026.

Seeking WHO EUL–Novavax said September 23 that together with its partner, Serum Institute of India (SII), it has applied for emergency use listing (EUL) of NVX-CoV2373 with to the World Health Organization (WHO). The submission to WHO is based on the companies’ previous regulatory submission to the Drugs Controller General of India (DCGI).

The companies added that in August, they completed the submission of modules required by regulatory agencies in India, Indonesia and the Philippines to initiate review of the vaccine, including preclinical, clinical, and chemistry, manufacturing and controls (CMC) data.

FDA Submission Delayed to Q4—Novavax CEO Stanley Erck told analysts on the company’s quarterly eanrings call August 5 that it plans to submit its BLA for NVX-CoV2373 to the FDA “hopefully early” in the fourth quarter, a quarter later than previously anticipated.

“It’s a matter of getting validation work done” in order to show the FDA that it has achieved consistency in its manufacturing process, Erck told Reuters.

Investors responded by sending Novavax shares down nearly 10% in after-hours trading, to $213.07 as of 7:59 p.m. ET from $236.20 at the close of trading on August 5.

Filings Completed, Planned—Novavax said it filed regulatory submissions in partnership with Serum Institute of India (SII) for emergency use authorization in multiple markets—including India, where the company submitted regulatory filings with the Drugs Controller General of India (DCGI), as well as Indonesia and the Philippines. The company expects to file for Emergency Use Listing with the World Health Organization in August, and complete to complete its regulatory filing with the UK Medicines and Healthcare products Regulatory Agency (MHRA) in the third quarter.

Within weeks of MHRA filing, Novavax added, it expects to complete additional regulatory filings with the European Medicines Agency (EMA) and regulatory agencies in Australia, Canada, and New Zealand.

Positive Booster Data—Novavax on August 5 announced preliminary data that it said showed a single booster dose of NVX-CoV2373, given six months after an initial two-dose regimen, elicited a 4.6-fold increase in functional antibody titers 28 days after boosting. Additionally, functional ACE-2 binding inhibition antibodies cross-reactive with the Delta (B.1.617.2) variant were more than 6-fold higher than the primary vaccination series.

The data was generated in an ongoing Phase II study in the U.S. and Australia in which select participants in the 5-microgram dose cohort received a 5-microgram booster dose 189 days after the initial two-dose regimen to examine functional immune response.

Novavax said it will post complete data from the study to a preprint server, and ultimately publish the data in a peer-review publication.

EU Purchase Agreement—Novavax said August 4 that it reached agreement with the European Commission for the purchase of up to 200 million doses of NVX-CoV2373. The agreement—whose value was not disclosed—covers the purchase of up to 100 million doses of the vaccine, with the option for an additional 100 million doses through 2023. The company added that it was working to complete its rolling submission for NVX-CoV2373 to the European Medicines Agency in the third quarter, with delivery of initial doses expected to begin following approval.

Phase III Data Published—Novavax researchers on June 30 published data in The New England Journal of Medicine from a Phase III trial in the U.K. (EudraCT number 2020-004123-16). The data showed that a two-dose regimen of NVX-CoV2373 administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. A post hoc analysis showed an efficacy of 86.3% against the B.1.1.7 (Alpha) variant and 96.4% against non-B.1.1.7 variants.

The randomized, observer-blinded, placebo-controlled study, led by researchers at St George’s, University of London and St George’s Hospital, London, enrolled 15,187 adults at 33 trial sites across the U.K.

FDA Filing Planned After Positive Phase III Data—Novavax said June 14 it will file for FDA approvals in the third quarter for its COVID-19 vaccine NVX-CoV2373 after it showed 90.4% overall efficacy, and 93% efficacy against the five most prevalent SARS-CoV-2 variants “of concern” and eight more variants “of interest,” in a Phase III trial.

Overall efficacy data from Novavax’s PREVENT-19 pivotal Phase III trial (NCT04611802) met the study’s primary endpoint—first occurrence of PCR-confirmed symptomatic (mild, moderate or severe) COVID-19 with onset at least 7 days after the second dose in serologically negative (to SARS-CoV-2) adult participants at baseline. In PREVENT-19, 77 COVID-19 cases were seen—63 in the placebo group and 14 in the vaccine group. All cases observed in the vaccine group were mild as defined by the trial protocol.vaccines

The vaccine demonstrated 100% protection against moderate and severe disease, based on 10 moderate cases and four severe cases being observed, all in the placebo group. NVX-CoV2373 also showed 91% efficacy in “high-risk” populations (defined as over age 65, under age 65 with certain comorbidities or having life circumstances with frequent COVID-19 exposure). Thirteen COVID-19 cases were reported in patients treated with the vaccine, and the other 62, with placebo.

In addition, PREVENT-19 met a key exploratory endpoint of the study by showing 93.2% efficacy against both “variants of concern” (VoC) and “variants of interest (VoI).

Immunogenicity, Protection vs. 2 Variants—Novavax on June 11 said NVX-CoV2373 and a new vaccine directed against variants showed strong immunogenicity and protection against two SARS-CoV-2 variants—B.1.1.7 (Alpha/U.K.) and B.1.351 (Beta/South Africa)—in three studies by researchers from the company and University of Maryland School of Medicine. One study was conducted in mice, another in baboon, and a third in human samples.

The researchers posted data from the studies in a preprint posted June 9 in bioRxiv. The findings showed:

  • Novavax’s new vaccine based on the recombinant spike protein antigen (rS-B.1.351) from Beta was highly immunogenic in mice and produced neutralizing antibodies.
  • Primates boosted with rS-B.1.351 induced strong neutralizing immune response to original SARS-CoV-2, Alpha and Beta.
  • Humans immunized with original NVX-CoV2373 vaccine demonstrated robust antibody responses to original SARS-CoV-2 strain, as well as to Alpha and Beta.

“These data suggest that not only could one booster dose of this variant-directed vaccine potentially provide a robust, protective immune boost after vaccination against the original SARS-CoV-2 virus, but also the potential to provide broad protection against various virus strains if used as a primary vaccine regimen,” said Gregory M. Glenn, MD, Novavax’s President of Research and Development.

Q3 EUA Filing Planned—Novavax stated May 10 it intends to file for emergency use authorization (EUA) of NVX-CoV2373 during the third quarter—when it also intends to pursue authorizations with the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).

The company pushed back its timeline, which previously called for seeking an FDA EUA in the second quarter, due to delays in getting manufacturing data involving quality, consistency, and stability tests for manufacturing and storage of the vaccine, President and CEO Stanley C. Erck told CNN.

A final analysis of data from the Phase III PREVENT-19 trial (NCT04611802), will be reported in the second quarter, Novavax added.

On May 6, Novavax said that it finalized an advance purchase agreement with Gavi, the Vaccine Alliance (Gavi) for supply of its recombinant protein-based COVID-19 vaccine candidate to the COVAX Facility. Under the APA, Novavax is expected to manufacture and distribute 350 million doses of NVX-CoV2373 to countries participating under the COVAX Facility, established to allocate and distribute vaccines equitably to participating countries and economies. Under a separate purchase agreement with Gavi, the Serum Institute of India is expected to manufacture and deliver the balance of the 1.1 billion doses of NVX-CoV2373, Novavax said.

On May 3, Novavax began a pediatric expansion of its Phase III clinical trial for NVX-CoV2373. The additional arm of the ongoing PREVENT-19 pivotal trial is designed to assess the efficacy, safety, and immunogenicity of NVX-CoV2373 in up to 3,000 adolescents aged 12-17 across up to 75 sites in the U.S.

Participants in the pediatric expansion will randomly receive either the vaccine candidate or placebo in two doses, administered 21 days apart. Two-thirds of volunteers will receive intramuscular injections of the vaccine and one-third will receive placebo. A blinded crossover is planned to take place six months after the initial set of vaccinations to ensure that all trial participants receive active vaccine. Participants will be monitored for safety for up to two years following the final dose, Novavax said.

President Joe Biden on April 27 mentioned Novavax by name as one of several vaccine developers whose vaccines the U.S. is considering sending to India and other countries that need them: “The problem is right now we have to make sure we have other vaccines like Novavax and others coming on, probably.” Shares of Novavax jumped 16% on the news.

The Com-Cov trial led by the U.K.’s National Immunisation Schedule Evaluation Consortium (NISEC) and the Oxford Vaccine Group (University of Oxford) was expanded April 14 to include Moderna’s COVID-19 vaccine mRNA-1273 and Novavax’s NVX-CoV2373.

The trial was launched in February to assess the effect of combining doses of various vaccines. Participants initially received first doses of either AstraZeneca’s AZD1222 or Pfizer/BioNTech’s BNT162b2 (COMIRNATY® in Europe, with the vaccine switched for the second dose. Following the change, participants were to receive second doses of either the same vaccine as the first dose, AZD1222 or NVX-CoV2373.

Com-Cov’s six new arms each involve 175 people, bringing to 1,050 the total number of participants.

Novavax said April 5 that it began crossover arms in two ongoing clinical trials of NVX-CoV2373, designed to ensure administration of active vaccine to all participants in the studies. Crossover has begun for Novavax’s Phase IIb trial in South Africa and its pivotal Phase III trial in the United Kingdom.

Novavax also plans a crossover in the Phase III PREVENT-19 trial, for which the company said it expected to read out initial clinical data during the second quarter. Novavax also said it plans to expand PREVENT-19 to include pediatric and adolescent arms, which are also expected to begin in the second quarter.

GlaxoSmithKline (GSK) said March 29 it had reached an agreement in principle with Novavax and the U.K. Vaccines Taskforce to support manufacturing of up to 60 million doses of NVX-CoV2373 for use nationwide, for an undisclosed price.

GSK agreed to provide fill and finish manufacturing capacity at its Barnard Castle facility in the North East of England beginning as early as May 2021, with the companies agreeing to begin technology transfer immediately. They and the Task Force agreed to negotiate a final agreement to include additional terms and conditions. The protein antigen component of NVX-CoV2373 is also produced in the North East of England by Novavax’ manufacturing partner, FUJIFILM Diosynth Biotechnologies, at its site in Billingham, Stockton-on-Tees.

Novavax has delayed the signing of a contract to supply its COVID-19 vaccine to the European Union, Reuters reported March 25, citing an unnamed “EU official involved in the talks.” A Novavax spokeswoman told the news agency that talks were continuing, and that the company was working the company was working “through some pandemic-related raw materials supply shortages,” without elaborating about either. The EU had been expected earlier this year to procure 100 million doses of Novavax’s COVID-19 vaccine.

Novavax on March 11 announced final efficacy of 96.4% against mild, moderate and severe disease caused by the original COVID-19 strain in a pivotal Phase III trial in the U.K. of NVX–CoV2373. The study enrolled more than 15,000 participants between 18-84 years of age, including 27% over the age of 65.

The company also announced the complete analysis of its Phase IIb trial in South Africa, showing the vaccine had an efficacy of 55.4% among a cohort of HIV-negative trial participants, and an overall efficacy of 48.6% against predominantly variant strains of SARS-CoV-2 among 147 PCR-positive cases (51 cases in the vaccine group and 96 in the placebo group). Across both trials, NVX-CoV2373 demonstrated 100% protection against severe disease, including all hospitalization and death.

Philippines officials said March 10 that they secured 30 million doses of NVX-CoV2373 through an agreement with the Serum Institute of India, the second vaccine deal signed by the national government, according to Agence France-Presse. The first was with AstraZeneca for 2.6 million doses of its vaccine, developed with Oxford University.

The Novavax vaccine will be available from the third quarter, at a price that has yet to be finalized. The government hopes to secure 148 million doses this year from seven companies—enough for around 70% of its population.

In announcing fourth quarter and full-year 2020 results on March 1, Novavax said it could file for an emergency use authorization with the FDA in the second quarter of 2021. Novavax hopes it can use data from its Phase III U.K. clinical trial in its FDA submission, and expects the FDA to examine data in May, a month after they are reviewed by regulators in the U.K., President and CEO Stanley C. Erck said on CNBC. Should the FDA insist on waiting for U.S. data, the agency may push the review timeline by one or two months, he added.

The company also said that NVX-CoV2373 showed 95.6% efficacy against the original strain of COVID-19 and 85.6% against the UK variant strain, and re-stated an earlier finding that its vaccine met the Phase III trial’s primary endpoint met with an efficacy rate of 89.3%.

Novavax said February 26 that it signed an exclusive license agreement with Takeda Pharmaceutical for Takeda to develop, manufacture, and commercialize NVX-CoV2373 in Japan.

Novavax agreed to transfer the technology for manufacturing of the vaccine antigen and will supply its Matrix-M™ adjuvant to Takeda. Takeda anticipated the capacity to manufacture over 250 million doses of the COVID-19 vaccine per year. Takeda agreed in return to pay Novavax undisclosed payments tied to achieving development and commercial milestones, plus a portion of proceeds from the vaccine.

Takeda also disclosed that it dosed the first participants in a Phase II clinical trial to test the immunogenicity and safety of Novavax’ vaccine candidate in Japanese participants.

Novavax on February 18 announced a memorandum of understanding with Gavi, the Vaccine Alliance (Gavi), to provide 1.1 billion cumulative doses of NVX-CoV2373 for the COVAX Facility. Gavi leads the design and implementation of the COVAX Facility, created to supply vaccines globally, and has committed to working with Novavax to finalize an advance purchase agreement for vaccine supply and global distribution allocation via the COVAX Facility and its partners.

The doses will be manufactured and distributed globally by Novavax and Serum Institute of India (SII), the latter under an existing agreement between Gavi and SII.

Novavax and SK Bioscience said February 15 that they expanded their collaboration and license agreement, with SK finalizing an agreement to supply 40 million doses of NVX-CoV2373 to the government of South Korea beginning in 2021, for an undisclosed price. SK also obtained a license to manufacture and commercialize NVX-CoV2373 for sale to South Korea, as a result of which SK said it will add significant production capacity.

The agreement also calls on Novavax to facilitate technology transfer related to the manufacturing of its protein antigen, its Matrix M adjuvant, and support to SK Bioscience as needed to secure regulatory approval.

Rolling review begins—On February 4, Novavax announced it had begun a rolling review process for authorization of NVX-CoV2373 with several regulatory agencies worldwide, including the FDA, the European Medicines Agency, the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), and Health Canada. The reviews will continue while the company completes its pivotal Phase III trials in the U.S. and U.K., and through initial authorization for emergency use granted under country-specific regulations, and through initial authorization for emergency use.

A day earlier, Novavax executed a binding Heads of Terms agreement with the government of Switzerland to supply 6 million doses of NVX-CoV2373, to the country. Novavax and Switzerland plan to negotiate a final agreement, with initial delivery of vaccine doses slated to ship following successful clinical development and regulatory review.

On January 28, Novavax electrified investors by announcing that its COVID-19 vaccine NVX-CoV2373 showed efficacy of 89.3% in the company’s first analysis of data from a Phase III trial in the U.K., where a variant strain (B.1.1.7) accounted for about half of all positive cases.

However, NVX-CoV2373 achieved only 60% efficacy in a Phase IIb trial in South Africa, where that country’s escape variant of the virus (B.1.351, also known as 20H/501Y.V2) was seen in 90% of cases, Novavax said.

Novavax said January 7 it executed an Advance Purchase Agreement with the Commonwealth of Australia for 51 million doses of NVX-CoV2373 for an undisclosed price, with an option to purchase an additional 10 million doses—finalizing an agreement in principle announced in November 2020. Novavax said it will work with Australia’s Therapeutics Goods Administration (TGA), to obtain approvals upon showing efficacy in clinical studies. The company aims to deliver initial doses by mid-2021.

2020 Status: Phase III trial launched—Novavax said December 28 that it launched the pivotal Phase III PREVENT-19 trial (NCT04611802) in the U.S. and Mexico to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373. The randomized, placebo-controlled, observer-blinded study will assess the efficacy, safety and immunogenicity of NVX-CoV2373 in up to 30,000 participants 18 years of age and older compared with placebo. The trial’s primary endpoint is the prevention of PCR-confirmed, symptomatic COVID-19. The key secondary endpoint is the prevention of PCR-confirmed, symptomatic moderate or severe COVID-19. Both endpoints will be assessed at least seven days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2.

Two thirds of the participants will be assigned to randomly receive two intramuscular injections of the vaccine, administered 21 days apart, while one third of the trial participants will receive placebo. Trial sites were selected in locations where transmission rates are currently high, to accelerate the accumulation of positive cases that could show efficacy. Participants will be followed for 24 months following the second injection

PREVENT-19 is being conducted with support from federal agencies involved in Operation Warp Speed, the Trump administration’s effort to promote development and distribution of COVID-19 vaccines and drugs. Those agencies include the Department of Defense (DoD), the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advanced Research and Development Authority (BARDA)—which has committed up to $1.6 billion to Novavax under a DoD agreement (identifier MCDC OTA agreement number W15QKN-16-9-1002).

Novavax is also conducting a pivotal Phase III study in the United Kingdom, a Phase IIb safety and efficacy study in South Africa, and an ongoing Phase I/II trial in the U.S. and Australia. Data from these trials are expected as soon as early first quarter 2021, though timing will depend on transmission rates in the regions, the company said.

Novavax said November 9 that the FDA granted its Fast Track designation for NVX-CoV2373. By the end of November, the company expected to finish enrollment in its Phase III U.K. trial, with interim data in that study expected as soon as early first quarter 2021.

Five days earlier, Novavax signed a non-binding Heads of Terms document with the Australian government to supply 40 million doses of NVX-CoV2373 to Australia starting as early as the first half of 2021, subject to the successful completion of Phase III clinical development and approval of the vaccine by Australia’s Therapeutic Goods Administration (TGA). The vaccine regimen is expected to require two doses per individual, administered 21 days apart.

Australia joins the U.S., the U.K., and Canada in signing direct supply agreements with Novavax. The company is supplying doses in Japan, South Korea, and India through partnerships. Australian clinical researchers led the global Phase I clinical trial in August, which involved 131 Australians across two trial sites (Melbourne and Brisbane). Also, approximately 690 Australians have participated in the Phase II arm of the clinical trial, which has been conducted across up to 40 sites in Australia and the U.S.

Novavax joined officials in its headquarters city of Gaithersburg, MD, on November 2 to announce expansion plans. The company plans to take 122,000 square feet of space at 700 Quince Orchard Road, and has committed to adding at least 400 local jobs, nearly doubling its current workforce of 450 worldwide. Most of the new jobs are expected to be added b March 2021.

Maryland’s Department of Commerce—which has prioritized assistance to life sciences companies—approved a $2 million conditional loan tied to job creation and capital investment. The state has also approved a $200,000 Partnership for Workforce Quality training grant, and the company is eligible for several tax credits, including the Job Creation Tax Credit and More Jobs for Marylanders.

Additionally, Montgomery County has approved a $500,000 grant tied to job creation and capital investment, while the City of Gaithersburg said it will approve a grant of up to $50,000 from its Economic Development Opportunity Fund. The city accelerated its planning approval process to accommodate Novavax’ timeline, given the company’s role in fighting COVID-19 and resulting assistance from Operation Warp Speed, the Trump administration’s effort to accelerate development of COVID-19 vaccines.

On October 27, Novavax said that it had enrolled 5,500 volunteers in the Phase III U.K. trial, which has been expanded from 10,000 to 15,000 volunteers. The increased enrollment “is likely to facilitate assessment of safety and efficacy in a shorter time period,” according to the company.

The trial, which is being conducted with the U.K. Government’s Vaccines Taskforce, was launched in September and is expected to be fully enrolled by the end of November, with interim data expected by early first quarter 2021, depending on the overall COVID-19 attack rate. Novavax has posted the protocol for the Phase III U.K. trial online. The protocol calls for unblinding of data once 152 participants have achieved mild, moderate or severe endpoints. Two interim analyses are planned upon occurrence of 66 and 110 endpoints.

Novavax also said it expects to launch a second Phase III trial designed to enroll up to 30,000 participants in the U.S. and Mexico by the end of November—a study funded through the U.S. government’s Operation Warp Speed program. The patient population will reflect proportional representation of diverse populations most vulnerable to COVID-19, across race/ethnicity, age, and co-morbidities.

The company cited progress toward large-scale manufacturing while acknowledging delays from original timeframe estimates. Novavax said it will use its contract manufacturing site at FUJIFILM Diosynth Biotechnologies’ Morrisville, NC facility to produce material for the U.S. trial.

On September 25, Novavax entered into a non-exclusive agreement with Endo International subsidiary Par Sterile Products to provide fill-finish manufacturing services at its plant in Rochester, MI, for NVX-CoV2373. Under the agreement, whose value was not disclosed, the Rochester facility has begun production of NVX-CoV2373 final drug product, with initial batches to be used in Novavax’ Phase III clinical trial in the U.S. Par Sterile will also fill-finish NVX-CoV2373 vaccine intended for commercial distribution in the U.S.

A day earlier, Novavax launched the U.K. trial. The randomized, placebo-controlled, observer-blinded study to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373 with Matrix-M in up to 10,000 subjects 18-84 years of age, with and without “relevant” comorbidities, over the following four to six weeks, Novavax said. Half the participants will receive two intramuscular injections of vaccine comprising 5 µg of protein antigen with 50 µg Matrix‑M adjuvant, 21 days apart, while half of the trial participants will receive placebo. At least 25% of the study population will be over age 65.

The trial’s first primary endpoint is first occurrence of PCR-confirmed symptomatic COVID-19 with onset at least seven days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2. The second primary endpoint is first occurrence of PCR-confirmed symptomatic moderate or severe COVID-19 with onset at least seven days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2

“The data from this trial is expected to support regulatory submissions for licensure in the UK, EU and other countries,” stated Gregory M. Glenn, M.D., President, Research and Development at Novavax.

Maryland Gov. Larry Hogan joined state Secretary of Commerce Kelly M. Schulz and local officials in marking the launch of Phase III studies with a tour of the company’s facilities in Gaithersburg: “The coronavirus vaccine candidate that’s been developed by Novavax is one of the most promising in the country, if not the world.”

On August 31, Novavax reached an agreement in principle with the government of Canada to supply up to 76 million doses of NVX-CoV2373. The value was not disclosed. Novavax and Canada did say that they expect to finalize an advance purchase agreement under which Novavax will agree to supply doses of NVX-CoV2373 to Canada beginning as early as the second quarter of 2021.

The purchase arrangement will be subject to licensure of the NVX-CoV2373 by Health Canada, Novavax said. The vaccine is in multiple Phase II clinical trials: On August 24, Novavax said the first volunteers had been enrolled in the Phase II portion of its ongoing Phase I/II clinical trial (NCT04368988), designed to evaluate the immunogenicity and safety of two doses of of NVX-CoV2373 (5 and 25 µg) with and without 50 µg of Matrix‑M™ adjuvant in up to 1,500 volunteers ages 18-84.

The randomized, placebo-controlled, observer-blinded study is designed to assess two dose sizes (5 and 25 µg) of NVX-CoV2373, each with 50 µg of Matrix‑M. Unlike the Phase I portion, the Phase II portion will include older adults 60-84 years of age as approximately half of the trial’s population. Secondary objectives include preliminary evaluation of efficacy. The trial will be conducted at up to 40 sites in the U.S. and Australia, Novovax said.

NVX-CoV2373 is in a pair of Phase II trials launched in August—including a Phase IIb study in South Africa to assess efficacy, and a Phase II safety and immunogenicity study in the U.S. and Australia.

On August 14, the U.K. government agreed to purchase 60 million doses of NVX-CoV2373 from the company, and support its planned Phase III clinical trial in the U.K., through an agreement whose value was not disclosed. The doses are set to be manufactured as early as the first quarter of 2021.

The trial will be designed to evaluate the ability of NVX-CoV2373 to protect against symptomatic COVID-19 disease as well as evaluate antibody and T-cell responses. The randomized, double-blind, placebo-controlled efficacy study will enroll approximately 9,000 adults 18-85 years of age in the U.K., and is expected to start in the third quarter.

Novavax also said it will expand its collaboration with FUJIFILM Diosynth Biotechnologies (FDB), which will manufacture the antigen component of NVX-CoV2373 from its Billingham, Stockton-on-Tees site in the U.K., as well as at U.S. sites in Morrisville, NC, and College Station, TX. FDB’s U.K. sitevis expected to produce up to 180 million doses annually.

On August 13, Novavax said it signed a development and supply agreement for the antigen component of NVX-CoV2373 with Seoul-based SK bioscience, a vaccine business subsidiary of SK Group. The agreement calls for supply to global markets that include the COVAX Facility, co-led by Gavi, the Coalition for Epidemic Preparedness Innovations (CEPI) and the World Health Organization.

Novavax and SK signed a letter of intent with South Korea’s Ministry of Health and Welfare to work toward broad and equitable access to NVX-CoV2373 worldwide, as well as to make the vaccine available in South Korea. SK bioscience agreed to manufacture the vaccine antigen component for use in the final drug product globally during the pandemic, at its vaccine facility in Andong L-house, South Korea, beginning in August. The value of the agreement was not disclosed.

On August 7, Novavax licensed its COVID-19 vaccine technology to Takeda Pharmaceutical through a partnership by which Takeda will develop, manufacture, and commercialize NVX‑CoV2373 in Japan, using Matrix-M adjuvant to be supplied by Novavax. Takeda will also be responsible for regulatory submission to Japan’s Ministry of Health, Labour and Welfare (MHLW).

MHLW agreed to provide funding to Takeda—the amount was not disclosed in the companies’ announcement—for technology transfer, establishment of infrastructure, and scale-up of manufacturing. Takeda said it anticipated the capacity to manufacture over 250 million doses of NVX‑CoV2373 per year.

Five days earlier, Serum Institute of India agreed to license rights from Novavax to NVX‑CoV2373 for development and commercialization in India as well as low- and middle-income countries (LMIC), through an agreement whose value was not disclosed. Novavax retains rights to NVX-CoV2373 elsewhere in the world.

Novavax and Serum Institute of India agreed to partner on clinical development, co-formulation, filling and finishing and commercialization of NVX-CoV2373. Serum Institute will oversee regulatory submissions and marketing authorizations in regions covered by the collaboration. Novavax agreed to provide both vaccine antigen and Matrix‑M adjuvant, while the partners said they were in talks to have the Serum Institute manufacture vaccine antigen in India. Novavax and Seerum Institute plan to split the revenue from the sale of product, net of agreed costs.

A day earlier, Novavax announced positive results from the Phase I portion of its Phase I/II clinical trial (NCT04368988), designed to evaluate two doses of NVX-CoV2373 (5 and 25 µg) with and without Matrix‑M™ adjuvant in 131 healthy adults ages 18-59. NVX-CoV2373, adjuvanted with Matrix-M, elicited robust antibody responses numerically superior to human convalescent sera, according to data submitted for peer-review to a scientific journal.

All participants developed anti-spike IgG antibodies after a single dose of vaccine, Novavax said, many also developing wild-type virus neutralizing antibody responses. After the second dose, all participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease, the company said—adding that IgG antibody response was highly correlated with neutralization titers, showing that a significant proportion of antibodies were functional.

For both dosages of NVX‑CoV2373 with adjuvant, the 5 µg dose performed “comparably” with the 25 µg dose, Novavax said. NVX‑CoV2373 also induced antigen-specific polyfunctional CD4+ T cell responses with a strong bias toward the Th1 phenotype (IFN-g, IL-2, and TNF-a).

Based on an interim analysis of Phase I safety and immunogenicity data, the trial was expanded to Phase II clinical trials in multiple countries, including the U.S. The trial—which began in Australia in May—is being funded by up-to $388 million in funding from the Coalition for Epidemic Preparedness Innovations (CEPI). If the Phase I/II trial is successful, CEPI said, it anticipates supporting further clinical development that would advance NVX-CoV2373 through to licensure.

On July 23, Novavax joined FDB to announce that FDB will manufacture bulk drug substance for NVX-CoV2373, under an agreement whose value was not disclosed. FDB’s site in Morrisville, NC has begun production of the first batch of NVX-CoV2373. Batches produced at FDB’s Morrisville site will be used in Novavax’s planned pivotal Phase III clinical trial, designed to assess NVX-CoV2373 in up to 30,000 participants, and set to start this fall.

The Phase III trial is among R&D efforts to be funded through the $1.6 billion awarded in July to Novavax through President Donald Trump’s “Operation Warp Speed” program toward late-stage clinical trials and large-scale manufacturing to produce 100 million doses of its COVID-19 vaccine by year’s end. Novavax said the funding will enable it to complete late-stage clinical studies aimed at evaluating the safety and efficacy of NVX-CoV2373.

In June, Novavax said biotech investor and executive David Mott was joining its board as an independent director, after recently acquiring nearly 65,000 shares of the company’s common stock. Also, Novavax was awarded a $60 million contract by the U.S. Department of Defense (DoD) for the manufacturing of NVX‑CoV2373. Through the Defense Health Program, the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense Enabling Biotechnologies (JPEO-CBRND-EB) agreed to support production of several vaccine components to be manufactured in the U.S.  Novavax plans to deliver this year for DoD 10 million doses of NVX‑CoV2373 that could be used in Phase II/III trials, or under an Emergency Use Authorization (EUA) if approved by the FDA.

Also in June, AGC Biologics said it will partner with Novavax on large-scale GMP production of Matrix-M– significantly increasing Novavax’ capacity to deliver doses in 2020 and 2021—through an agreement whose value was not disclosed. And Novavax joined The PolyPeptide Group to announce large-scale GMP production by the global CDMO of two unspecified key intermediate components used in the production of Matrix-M.

In May, Novavax acquired Praha Vaccines from the India-based Cyrus Poonawalla Group for $167 million cash, in a deal designed to ramp up Novavax’s manufacturing capacity for NVX-CoV2373. Praha Vaccines’ assets include a 150,000-square foot vaccine and biologics manufacturing facility and other support buildings in Bohumil, Czech Republic. Novavax said the Bohumil facility is expected to deliver an annual capacity of over 1 billion doses of antigen starting in 2021 for the COVID-19 vaccine.

The Bohumil facility is completing renovations that include the addition of Biosafety Level-3 (BSL-3) capabilities. The site’s approximately 150 employees with “significant experience” in vaccine manufacturing and support have joined Novavax, the company said.

On May 11, Novavax joined CEPI in announcing up to $384 million in additional funding for the company toward clinical development and large-scale manufacturing of NVX-CoV2373. CEPI agreed to fund preclinical as well as Phase I and Phase II studies of NVX-CoV2373. The funding multiplied CEPI’s initial $4 million investment in the vaccine candidate, made two months earlier. Novavax’s total $388 million in CEPI funding accounted for 87% of the total $446 million awarded by the Coalition toward COVID-19 vaccine R&D as of that date.

Novavax identified its COVID-19 vaccine candidate in April. The company said NVX-CoV2373 was shown to be highly immunogenic in animal models measuring spike protein-specific antibodies, antibodies that block the binding of the spike protein to the receptor, and wild-type virus neutralizing antibodies. High levels of spike protein-specific antibodies with ACE-2 human receptor binding domain blocking activity and SARS-CoV-2 wild-type virus neutralizing antibodies were also seen after a single immunization.

In March, Emergent Biosolutions disclosed it retained an option to allocate manufacturing capacity for an expanded COVID-19 program under an agreement with Novavax to provide “molecule-to-market” contract development and manufacturing (CDMO) services to produce Novavax’s NanoFlu™, its recombinant quadrivalent seasonal influenza vaccine candidate.

Earlier in March, Emergent announced similar services to support clinical development of Novavax’s COVID-19 vaccine candidate, saying March 10 it agreed to produce the vaccine candidate and had initiated work, anticipating the vaccine candidate will be used in a Phase I study within the next four months. In February, Novavax said it had produced and was assessing multiple nanoparticle vaccine candidates in animal models prior to identifying an optimal candidate for human testing.

COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:


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