Candidate: Adjuvanted vaccine for COVID-19
Type: Vaccine incorporating Sanofi’s S-protein COVID-19 antigen, which is based on recombinant DNA technology; and GSK’s pandemic AS03 adjuvant
2021 Status: Phase III Trial Begins–Sanofi and GlaxoSmithKline (GSK) said May 27 they began enrollment in a Phase III trial designed to assess the safety, efficacy, and immunogenicity of their adjuvanted recombinant-protein COVID-19 vaccine candidate. The global, randomized, double-blind placebo-controlled study will include more than 35,000 volunteers aged 18 and older from several countries, including sites in the U.S., Asia, Africa, and Latin America.
Sanofi and GlaxoSmithKline (GSK) said February 22 they had begun a new mid-stage study of a “refined” formulation of their adjuvanted recombinant protein-based candidate, with plans to advance to Phase III next quarter and reach the market by year’s end. The companies began testing their COVID-19 vaccine candidate in a Phase II trial (VAT00002; NCT04762680) that is expected to recruit 720 volunteer participants ages 18 and older, with the goal of selecting the most appropriate antigen dosage for a Phase III study expected to begin in the second quarter.
Should the results of that study prove positive, the companies said, they will pursue approvals designed to bring the vaccine to patients during the fourth quarter, Sanofi and GSK said.
2020 Status: Availability delayed after clinical setback—Sanofi and GSK on December 11 acknowledged that their vaccine would not be available until the fourth quarter of 2021 following a clinical setback: Phase I/II interim results showed that the vaccine generated insufficient neutralizing antibody titers in adults over the age of 50, “likely due to an insufficient concentration of the antigen.” Volunteers were accidentally given lower doses than intended in initial clinical trials due to a miscalculation in the manufacturing process, Thomas Triomphe, Sanofi’s executive vice president for vaccines, told The Wall Street Journal.
In adults aged 18 to 49 years, the vaccine showed an immune response comparable to patients who recovered from COVID-19.
Sanofi and GSK said they will reformulate the vaccine, then launch a Phase IIb study with an improved antigen formulation in February, to be funded through Operation Warp Speed, which has awarded the companies up to $2.07 billion in funding. . The study will include a proposed comparison with an authorized COVID-19 vaccine. Upon positive data, Sanofi and GSK plan to begin a global Phase III study in the second quarter of 2021. Positive results from this study would lead to regulatory submissions in the second half of 2021.
Sanofi and GSK said September 18 that they finalized and signed an advanced purchase agreement with the European Commission (EC) to supply up to 300 million doses of their COVID-19 vaccine to all its member states once it is approved. The companies added that the EU may donate reserved doses to lower- and middle-income countries—and will provide upfront funding to support scale-up of Sanofi and GSK manufacturing capabilities in Europe.
The companies said they intended to produce up to 1 billion doses per year.The antigen and final vaccine doses will be manufactured in European countries, Sanofi and GSK said, leveraging the company’s industrial sites in Belgium, Italy, Germany, and France.
Earlier in September, GSK and Sanofi said they launched an up-to-440 participant Phase I/II trial (NCT04537208), with a Phase III study planned to begin by the end of 2020. Participants from two age groups (adults ages 18-49 and adults ages 50+) will receive either one injection (Cohort 1) or two injections (Cohort 2) of study vaccine or placebo control.
Regulatory approval could be requested in the first half of 2021, the companies added.
The EC on July 31 said it concluded exploratory talks eith the companies, with the goal of eventually hammering out an Advance Purchase Agreement to be financed with the €2.7 billion ($3.2 billion) Emergency Support Instrument, which has funds dedicated to the creation of a portfolio of potential vaccines with different profiles and produced by different companies. The EC added that Sanofi and GSK planned to seek marketing authorization in June 2021, should Phase III clinical trials prove positive.
Also on July 31, Sanofi and GSK joined the U.S. Departments of Health and Human Services (HHS) to announce the companies were awarded up to $2.1 billion by the U.S. government toward developing and manufacturing their COVID-19 vaccine. HHS and the U.S. Department of Defense are providing the funding through Operation Warp Speed, the program by which President Donald Trump’s administration has committed the nation to delivering 300 million vaccine doses protecting against SARS-CoV-2 by January 2021.
Sanofi will receive the majority of the U.S. government funding, more than half of which is intended to support late-stage development of the vaccine, including a large-scale Phase III efficacy trial and other clinical studies, with the rest to be used toward manufacturing scale-up and delivery of an initial 100 million doses of the vaccine. The companies plan to launch a Phase I/II trial in September 2020, and the Phase III trial by year’s end.
The companies agreed to carry out fill-finish manufacturing in the U.S. so that vaccine doses are packaged and ready to ship immediately if clinical trials are successful and FDA authorizes use. While clinical trials are underway, HHS said, manufacturing efforts would begin with a demonstration project—a parallel effort intended to speed up vaccine development.
Two days earlier, GSK and Sanofi said they agreed to supply up to 60 million doses of their COVID-19 vaccine to the UK government. The companies added that they are in “active” ongoing discussions with the European Commission and various global organizations.
In addition, GSK and Sanofi plan to provide a “significant” portion of their total worldwide available supply capacity in 2021 and 2022 to “Access to COVID‐19 Tools (ACT) Accelerator,” a global collaboration designed to accelerate development, production, and equitable access to COVID-19 tests, treatments, and vaccines.
The World Health Organization is among global organizations in the ACT collaboration, along with the Bill & Melinda Gates Foundation; the Coalition for Epidemic Preparedness Innovations (CEPI); the Foundation for Innovative New Diagnostics (FIND); Gavi, The Vaccine Alliance; The Global Fund; Unitaid;, Wellcome; The World Bank; and the World-Bank-supported Global Financing Facility.
Sanofi on June 23 disclosed at its virtual R&D Day that it plans to accelerate its timeline for the recombinant protein-based vaccine being co-developed with GSK. Sanofi said it expected to begin a Phase I/II trial of the vaccine in September, and projected it could obtain approval by the first half of 2021 at the earliest.
In May, Sanofi CEO Paul Hudson told Bloomberg News on May 13 that the U.S. would see the first doses of the vaccine candidate before the company quickly clarified his remarks with a statement adding that vaccines made in the U.S. would be distributed there, while the rest of the world would be served by other sites.
Before that clarification, Hudson said Washington expected the first doses in return for the company receiving funding and support from the Biomedical Advanced Research and Development Authority (BARDA): “The U.S. government has the right to the largest pre-order because it’s invested in taking the risk.”
Hudson told analysts on the company’s quarterly conference call April 24 that GSK will be able to manufacture its pandemic AS03 adjuvant at a large scale.
“Existing manufacturing capacity in place today is up to 600 million doses and looking to double this and to have over a billion doses available by mid 2021,” Hudson said. “We’re planning to initiate clinical studies in Q4 2020 and aiming for approval in mid to second half of 2021.”
A week earlier, Hudson said on CNBC’s “Squawk Box” that it could produce up to 600 million doses of the vaccine next year if its studies with GSK advance as planned.
The companies announced their partnership in April, saying they planned to initiate Phase I trials in the second half of 2020 and, depending on clinical success and regulatory considerations, aimed to complete the development required for availability by the second half of 2021.
Sanofi and GSK also committed to making any vaccine developed through the collaboration “affordable to the public and through mechanisms that offer fair access for people in all countries.”
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: