Covid-19 vaccine developers remind the world that setbacks happen

As Biontech and Pfizer’s Covid-19 vaccine gets a positive US vote, delays for Sanofi, Glaxo and CSL show that top-speed drug development is the exception.

Policy and regulation

The swift progress made by Biontech/Pfizer and Moderna with their respective Covid-19 vaccines must have raised hopes that other projects would proceed with such speed. Setbacks revealed today from Sanofi/Glaxosmithkline and Australia's CSL serve as a reminder of the real risks of drug development.

At least BNT162b2, from Biontech and Pfizer, looks likely to be made available in the US in the coming days, in the wake of endorsement from an FDA advisory committee yesterday. Concerns were raised about lack of evidence in adolescents and troubling signals in people with severe allergies, but neither of these issues is likely to stay the agency’s hand.

Requests for further studies to address these and other gaps in the clinical data are a certainty. But for now, with 17 votes cast in favour and only four against, with one abstention, the rollout of BNT162b2 in the US is surely imminent. The UK and Canada have already issued their own authorisations.

The next big event for this space is Moderna’s similar hearing next Thursday, when once again the first glimpse at detailed data will come with the briefing documents in the days ahead of the meeting. Given the setbacks announced today it will be hoped that the mRNA-1273 receives a similarly positive review.

The first big dent

News of an extended timeline for the Sanofi and Glaxo project puts a serious dent in potential vaccine availability next year. The partners had said they could supply a billion doses in 2021, and many regions have placed substantial orders, although all of this was naturally predicated on the product actually working.

The partners have had to reformulate the vaccine after the first version failed to prompt a sufficient immune reaction in older subjects. Suboptimal amounts of antigen seems to have been the problem, and a phase IIb trial with the next-gen candidate will begin in February. Assuming all goes well from now, a finished product could be ready by the end of 2021, around six months later than originally planned.

At least the Sanofi/Glaxo project is still in the running, unlike an effort from Australia, being developed by CSL and the University of Queensland. This jab was found to cause participants to generate antibodies that interfered with certain HIV tests, and has been abandoned.

It is highly unlikely that this will be the last Covid-19 vaccine candidate to disappoint. And it is should be considered a positive that this signal was uncovered fairly early on in clinical development.

A final development in the vaccine space comes with news that Astrazeneca is considering combinations of various vaccines with AZD1222, developed with Oxford University. A statement described work to investigate heterologous boosting, a process whereby immune systems are primed with different types of vaccine that target the same antigen.

This is all very much in the exploratory stage, Astra told Vantage. However, Gamaleya Research Institute, developer of Russia’s Sputnik vaccine, was named as a collaborator.

It must be hoped that this does not signal any loss in confidence in AZD1222. However, with global demand still far outstripping what the leading candidates can hope to provide this year, it is not surprising that all avenues are being explored. 

Next steps for selected clinical-stage Covid-19 vaccines
Project  Description  Company  Update
BNT162b2  mRNA (2 dose) Pfizer/Biontech Positive FDA adcom; authorised in UK and Canada
mRNA-1273 mRNA (2 dose) Moderna December 17 FDA adcom; US and EU approvals expected by YE 2020
Sputnik V Adenovirus (2 dose) Gamaleya Research Institute/Russia Approved in Russia
AZD1222 Chimp adenovirus (2 dose) Astrazeneca UK and Brazil trials reported and being prepared for regulatory submissions; US trial due to report 2021
NVX-CoV2373 Recombinant nanoparticle (2 dose) Novavax Data from UK ph3 and S Africa ph2b due Q1'21; US/Mexico ph3 to start ~YE 2020
Ad26.COV2-S Adeno type 26 (1 & 2 dose) J&J Ph3 Ensemble (single dose) and Ensemble 2 (2-dose) recruiting; data 2021
CVnCoV mRNA (2 dose) Curevac Ph2 recruiting; ph2/3 to start ~YE 2020
COVID-19 S-Trimer Trimerised fusion protein (2 dose)  Clover/Glaxo Ph1 ongoing; ph2/3 to start YE 2020
Covid-19 vaccine project Recombinant protein (1 or 2 dose tbc)  Sanofi/Glaxo  Ph1 results due Dec 2020; ph3 start due ~YE 2020
V591 and V590  Measles virus vector and rVSV-based vaccine (1 dose targeted)  Merck  Ph1 immunogenicity data due ~YE 2020; ph3 to start 2021
v451 Adjuvanted molecular clamp recombinant protein vaccine CSL Abandoned Dec 2020
Source: EvaluatePharma, company statements. 

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