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COVID-19 vaccines that could report Phase III data before Moderna, Pfizer-BioNTech products become broadly available 

With EUAs coming soon for two COVID-19 vaccines, it could soon get harder to convince patients to enroll in trials of others. 

With EUAs coming soon for two COVID-19 vaccines, it could soon get harder to convince patients to enroll in trials of others.

Nov 19, 2020 | 2:05 AM GMT

Strong efficacy data from the two leading COVID-19 vaccines suggest the window for testing additional vaccine candidates in the U.S. could soon start to close. Of the more than 200 vaccines in development for COVID-19, at least seven have a chance of gathering pivotal data before the front-runners become broadly available, making recruitment difficult.

With protection rates of 95% and two-month safety data in or imminent, Moncef Slaoui, chief scientific adviser to Operation Warp Speed, said in a briefing Wednesday that he expects emergency use authorizations (EUAs) for BNT162b2 from Pfizer Inc. (NYSE:PFE) and BioNTech SE (NASDAQ:BNTX) and mRNA-1273 from Moderna Inc. (NASDAQ:MRNA) to come as early as the middle of December.

EUAs for the first candidates could hinder trial recruitment in at least two ways. Given the gravity of the pandemic, some stakeholders believe it would be ethical to unblind ongoing trials at that point to give subjects the opportunity to switch to a vaccine deemed effective. Even if unblinding doesn’t occur, as the two authorized vaccines start to become widely available, volunteering for clinical trials may become less attractive.

At an Operation Warp Speed briefing Wednesday, Slaoui implored U.S. citizens to participate in clinical trials.

“I do want to make a point here, a plea, frankly,” Slaoui said. “It's very likely that the other vaccines that are being tested will also be as effective or substantially as effective. I would really ask for the population of people who want to volunteer and help to come and participate into the clinical trials, because without their participation, it's impossible to know whether more vaccines can be demonstrated to be effective and safe and made available to the population.”

Testing a diverse set of vaccine candidates, based on different technologies, is vital to ensuring sufficient supply and could lead to products with tolerability and safety profiles that make them better suited, or more attractive, to subsets of the population.

Different vaccine antigens and technologies may also yield different durations of protection, a question that won’t be answered until long after the first products are on the market.

Slaoui argued that particpation in a clinical trial will still be the fastest way to get vaccinated for a period of time after the Pfizer-BioNTech and Moderna vaccines receive EUA.

“By the time the vaccine starts to be laid out you may, as an individual, only have access to the vaccine in a month and a half or two months. If you participate in a clinical trial, you have a 50% chance you have access to the vaccine tomorrow.”

Companies and modalities up next

Figure plots selected COVID-19 vaccines from BioCentury’s Coronavirus Resource Center for which Phase III plans and an intention to seek FDA approval have been disclosed. 

At the OWS briefing Wednesday, Slaoui said he expects the next two vaccines “will be giving us data on their efficacy in the weeks to come, maybe in early January for one of them and for the other it could be in the next few weeks.”

Slaoui was almost certainly talking about AZD1222 (ChAdOx1 nCoV-19) from AstraZeneca plc (LSE:AZN; NASDAQ:AZN) and JNJ-78436735 (Ad26.COV2.S) from Johnson & Johnson (NYSE:JNJ).

On Nov. 5, AstraZeneca said it had enrolled about 23,000 subjects into its two Phase III trials of AZD1222 (ChAdOx1 nCoV-19): a 40,000-subject U.S. trial and a 10,000-subject study in Brazil. Considering the pace at which the Moderna and Pfizer trials enrolled and read out, Phase III data for AZ’s program may not be far off. The company has started a rolling regulatory review in the EU.

J&J started its Phase III trial evaluating a single dose of JNJ-78436735 in September. Given the spiking infection rates around the globe, the pharma could have Phase III data by year-end. On Nov. 15, the pharma announced it was starting a second Phase III trial to test two doses of the candidate.

The J&J and AZ vaccines are both delivered via viral vectors, a rare modality for vaccines, and the Moderna and Pfizer-BioNTech vaccines are mRNA-based, a brand new vaccine modality. This means all four readouts will be key for establishing their respective technologies.

J&J’s JNJ-78436735 encodes the SARS-CoV-2 spike protein in an adenovirus serotype 26 (Ad26) vector, which is one of the two adenovirus vectors used in Sputnik V, the Russian vaccine reported to have 90% efficacy at an early interim analysis. AZ’s AZD1222, developed with the University of Oxford, uses a simian adenovirus vector dubbed ChAdOx1.

Sanofi (Euronext:SAN; NASDAQ:SNY) and Novavax Inc. (NASDAQ:NVAX) are both developing protein-based vaccines, a proven modality.

Sanofi hopes to start a Phase III trial by year-end of its protein-based SARS-CoV-2 vaccine and to apply for EUA in 1H21. Novavax expects data from a U.K. Phase III trial of NVX-CoV2373 in early 2021 and plans to begin a U.S. Phase III study by the end of the month. 

Inovio Pharmaceuticals Inc. (NASDAQ:INO) is gearing up to start a U.S. Phase II/III trial of DNA vaccine INO-4800 by year end.

After Moderna and Pfizer-BioNTech, CureVac N.V. (NASDAQ:CVAC) has the next most advanced mRNA vaccine. On Nov. 10, CureVac said it would start its Phase IIb/III trial of CVnCoV “in the coming weeks.” The trial will be conducted in Europe, Latin America, Africa and Asia.

Vaxxinity plans to begin Phase III testing of UB-612, a multitope peptide-based vaccine, in Brazil by year-end.

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