Yoshio Okubo, Senior Director, Head of Pandemic Global Product Team for Takeda Shares Insights on the Approval of its Covid-19 Vaccine

Shots:

Yoshio spoke about the approval of the Nuvaxovid COVID-19 Vaccine for Primary and Booster Immunization in Japan. Nuvaxovid Intramuscular Injection is the first recombinant protein-based COVID-19 vaccine approved for use in Japan
Yoshio also talked about Takeda’s collaboration with Novavax for the development, manufacturing, and commercialization of Nuvaxovid in Japan
Further, the interview highlighted the study design and key findings from the P-I/II clinical trial evaluating Nuvaxovid

Smriti: Can we start by discussing the details (MOA, ROA, formulations, etc.) of the Nuvaxovid vaccine?

Yoshio Okubo: Nuvaxovid® Intramuscular Injection (Nuvaxovid) is the first recombinant protein-based COVID-19 vaccine in Japan. The recombinant technology is used to create vaccine antigens in order to induce an immune response. The antigens are arranged around a nanoparticle core and then formulated with Matrix-M™ adjuvant to help enhance the immune system’s response to a vaccine. As a protein-based vaccine, it is designed to provoke an immune response without causing the disease.

The Ministry of Health, Labour and Welfare (MHLW) in Japan approved Nuvaxovid for primary and booster vaccination to prevent COVID-19 in individuals 18 years of age and older, and on July 22, 2022, the MHLW extended the approval of primary vaccination to include adolescents aged 12-17 years.

Smriti: Tell us more about your company’s collaboration with Novavax. Can we talk about their manufacturing technology which has been transferred to the Hikari facility and what is so unique about it?

Yoshio Okubo: Since the start of the pandemic, we have been committed to helping the world respond to COVID-19. Takeda assessed multiple SARS-CoV-2 vaccine and platform technologies using available public data. Our criteria included the technology platform, available clinical and safety data from other vaccines produced on this platform, and clinical, regulatory, and manufacturing timelines. As such, we partnered with Novavax in August 2020 to develop, manufacture, and commercialize Nuvaxovid at our Hikari facility in Japan.

Novavax transferred manufacturing technologies to enable Takeda to manufacture the vaccine antigen, while also supplying the Matrix-M adjuvant to Takeda. As Takeda had received a subsidy from the Government of Japan in 2011 to establish pandemic influenza manufacturing capability and build a large-scale facility in our Hikari plant, we were able to leverage the facility as much as possible to achieve technology transfer and regulatory approval of the vaccine in a very short time. We completed this process in less than two years, whereas the industry norm is approximately four years, as vaccines are one of the most complex biological products.

This partnership allows us to leverage our extensive and well-established global manufacturing and supply capabilities and build upon our existing support of influenza pandemic preparedness in Japan to deliver Nuvaxovid as an additional preventative option to those in Japan 12 years of age and older.

Smriti: Shed some light on the study design of the P-I/II clinical trial evaluating Nuvaxovid.

Yoshio Okubo: The approval of Nuvaxovid was based on our New Drug Application submission, which included positive interim results from our Phase 1/2 study of the vaccine in Japan.

The placebo-controlled study evaluated the safety and ability of the vaccine to provoke an immune response. The first 200 subjects aged 20 years and older were dosed in Japan in early 2021, and each participant was assigned to receive two doses of placebo or two 0.5 mL doses of Nuvaxovid given 21 days apart. Participants were followed for 12 months after the second dose.

Smriti: What were the key findings of the P-I/II clinical trial?

Yoshio Okubo: The early results of the study were acceptable, and two doses of the vaccine induced an anti-SARS-CoV-2 immune response which was consistent with results from overseas clinical studies in the U.K., U.S., Mexico, and Australia. No serious adverse events in the vaccine arm were reported, and the vaccine was well tolerated. Interim results have been published in Vaccine.

The final report of the Phase 1/2 study will be available for submission around quarter four later this calendar year.

Smriti: Can you please share the details of the trials and their results which have been shared with MHLW alongside with PhI/II study from Japan?

Yoshio Okubo: In addition to our Phase 1/2 study in Japan, the approval of Nuvaxovid was also based on Novavax’s two pivotal Phase 3 clinical trials in the U.K., U.S., and Mexico, as well as Phase 1/2 and Phase 2 studies in the U.S, Australia, and South Africa.

Novavax’s pivotal Phase 3 trial conducted in the U.K. was a randomized, observer-blinded, placebo-controlled trial conducted in more than 15,000 adults. The findings showed that a two-dose regimen of Nuvaxovid demonstrated 96.4% protection against the original COVID-19 virus strain, 86.3% against the Alpha (B.1.1.7) variant, and 89.7% efficacy overall, as well as a favorable safety and tolerability profile. Full results have been published in The New England Journal of Medicine.

The PREVENT-19 trial was a randomized, observer-blinded, placebo-controlled trial conducted on nearly 30,000 adults in the U.S. and Mexico. Participants were 18 years of age and older and randomized in a 2:1 ratio to receive two doses of Nuvaxovid or placebo 21 days apart. The trial achieved its primary endpoint of efficacy, demonstrated 100% protection against moderate and severe disease, and showed 90.4% efficacy overall, as well as a favorable safety and tolerability profile. Full results from the PREVENT-19 trial can be found in The New England Journal of Medicine.

Smriti: Take us through the funding Takeda received from MHLW & AMED Japan for the manufacturing of Nuvaxovid.

Yoshio Okubo: We received funding support from the MHLW for the technology transfer to enable the manufacturing of the vaccine at our Hikari facility, and the Japan Agency for Medical Research and Development (AMED) for the research and development of the vaccine in Japan and to obtain regulatory approval of Nuvaxovid in Japan.

Smriti: How much revenue from Nuvaxovid do you include in your FY2022 forecast?

Yoshio Okubo: We expect approximately 50-billion-yen revenue from both Nuvaxovid and Moderna’s vaccines in FY2022. We cannot disclose any breakdown between the two vaccines.

Smriti: Is Takeda planning or assessing this molecule in the younger population? Kindly share the details and timeline for the same.

Yoshio Okubo: On July 22, 2022, the MHLW extended the approval of primary vaccination to include adolescents aged 12-17 years in Japan. Takeda is working closely with Novavax to further expand Nuvaxovid’s indication to include a younger population and plans to submit clinical data from Phase 2b/3 Hummingbird™ clinical trial to support the age expansion in Japan.

Source: Canva

About the Author:

Yoshio Okubo is the Senior Director, Head of Pandemic Global Product Team for Takeda Vaccine Business. He leads Takeda’s pandemic preparedness, including influenza and COVID-19 vaccines. Prior to joining Takeda in 2015, Yoshio served in various leadership roles at Eisai, a Japanese pharmaceutical company. Currently, Takeda’s vaccines team is working on Nuvaxovid (P-III) for COVID-19, TAK-003 (P-IV) for Dengue, and TAK-426 (P-I) for the Zika virus.