Btobioinnovation.com

Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com

SPECIAL REPORT #21.4

COVID 19. Update #3

The past week news flow has been particularly rich with nevertheless three topics on the forefront:  vaccine supplies, rapid emergence of new SARS-CoV-2 variants, debate on the use of antibodies to treat high-risk patients.

Vaccine supplies.

As already mentioned in our last report, supply of sufficient vaccines is clearly becoming a major hurdle in many countries to achieve their forecasted vaccination campaigns. This now becomes particularly acute in the European Union, after both Pfizer and AstraZeneca have announced that their companies will not be able to deliver the expected doses in the European Union and in Canada, in the first quarter of 2021. Ten days ago, BioNTech and Pfizer had announced that they were scaling up for 2 billion vaccine doses, up from 1.3 billion doses previously, in upgrading their Belgium facility, but meeting this goal means supplies will run short temporarily in Europe and Canada.  The manufacturing upgrade will start to produce larger quantities of vaccine in mid-February. Both companies have engaged to deliver “significant more doses in the second quarter”. Reactions to the news came swiftly with six EU countries writing to both companies that the situation was “unacceptable”. “Not only does it impact the planned vaccination schedules, it also decreases the credibility of the vaccination process” the letter reads.

On Monday January 24, AstraZeneca informed the EU that its current production was not able to cope with the announced delivery schedules and the promised number of doses. The Anglo-Swedish company had originally closed a deal to pre-order 300 million doses with an option to add 100 million. The announcement of a slash to EU supplies from 80 million to 31 million doses, a roughly 60% reduction is now coming as a major concern of “vaccine nationalism” to favour Britain, a former EU member.  On Tuesday January 26, Pascal Soriot CEO of AstraZeneca told various newspapers the EU contract was based on a best-effort clause and did not commit the company to a specific timetable for deliveries. Soon after the EU Commission demanded AstraZeneca to make the contract public in full to remove mountain national frustrations. The roll out of the AstraZeneca vaccine was considered to be much easier than BioNTech/Pfizer’s COMINARTY. The restriction in the vaccine supply could significantly change the COVID-19’s vaccination strategy for many EU countries.

The same day, Sanofi, in an unusual move, announced that it will help manufacture more than 125 million doses of BioNTech and Pfizer COMINARTY vaccine, in lending spare production facilities at its Frankfurt (Germany) site. These additional doses will be used for EU countries with initial deliveries expected by August. “Since our main vaccine is a few months late, we asked ourselves how we could be of assistance now,” CEO Paul Hudson said in Le Figaro, a French newspaper. The temporary deal between companies, that are primarily competitors, is for one year only and reflects the urgency of quickly producing more vaccine doses for the EU.

An unexpected setback was announced by Merck who stopped the development of V590 and V591 two COVID-19 vaccines. The readout of the phase 1 clinical trials data showed that the immune responses to both clinical candidates were inferior to the natural responses seen in patients infected with SARS-CoV-2 and even more when compared to responses triggered by already approved vaccines. V590 is a vesicular virus vaccine co-developed with IAVI. V591 is a measles vector vaccine, first developed by the Institute Pasteur in Paris and accessed through the acquisition of Themis, an Austrian biotechnology company, last year. The failure of the two vaccine candidates means that Merck is leaving the COVID-19 vaccine race, although the company is not completely steeping away from the COVID-19 space. Its efforts are now focused at two therapeutics treatments: MK-7110 a fusion protein acquired from OncoImmune and molnupiravir, a RNA polymerase antiviral, partnered with Ridgeback-Bio.

Sanofi and Merck, two vaccine powerhouses who had collaborated for many years through their Sanofi Pasteur-MSD joint venture, had, last year, their executives using very similar narratives emphasising their proven and robust vaccine platforms and casting doubts on more experimental technologies such as mRNA or adenovirus. In addition, both CEOs were claiming that their companies would possibly come later but with more effective, easily scalable and one-dose vaccines, when they will be most needed.

New COVID-19 variants.

In spite of the rapid and sustained onset of vaccination campaigns in many Western countries the number of new COVID-19 cases and related death are again steadily increasing.  At the moment of writing the COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) from the Johns Hopkins University indicates 101,098,771 global cases with 2,180,867 global deaths with an increase of more than 18,000 deaths daily. According to the World Health Organisation both the British and the South African variants are far more contagious and possibly more deadly than the original one. The British variant, B.1.1.7, has been identified in 70 countries, the South African, B.1.351, in 31.

Both Pfizer and Moderna have indicated that their COVID-19 vaccines are working against the B.1.1.7 and the B.1.351 variants of SARS-CoV-2. In a laboratory test the BioNTech/Pfizer vaccine has demonstrated “no biological significant differences in neutralizing activity” between the original strain and the B.1.1.7 strain. Moderna found that in a study their own vaccine produces neutralising antibody titters against “all emerging variants”, although they observed a six-fold reduction in neutralising antibodies against the B.1.351 variant.  (A study published by Ho today claims a drop of efficacy of 6.5 fold for Pfizer and 8.6 fold for Moderna) “The two-dose regimen of the Moderna COVID-19 vaccine at the 100µg dose is expected to be protective against emerging strains detected to date” the company said. Moderna is also planning to test an additional booster dose of its vaccine and is advancing an emerging variant booster candidate against the B.1.351 variant.

Pfizer and BioNTech are also working on a booster.  “Every time a new variant comes up, we should be able to test whether or not our vaccine is effective,” Pfizer CEO Albert Bourla said .“Once we discover something that it is not as effective, we will very, very quickly be able to produce a booster dose that will be a small variation to the current vaccine.”

Using antibodies as “passive vaccination”.

The worldwide demand for COVID-19 vaccines continues to largely outstrip supplies and will do for quite a while with the delays and setbacks described above. The Johnson & Johnson vaccine results are due “early next week” and are highly anticipated to reinforce immunisation efforts.

New data release by Regeneron and Eli Lilly provide new support that combinations of engineered antibody cocktails can help prevent and even treat COVID-19 patients in various stages.

Regeneron’s REGEN-COV was 100% effective at preventing symptoms of COVID-10 in a phase 3 trial compared to placebo. “Passive vaccination” reduced the overall rate of infection by half. "Even with the emerging availability of active vaccines, we continue to see hundreds of thousands of people infected daily, actively spreading the virus to their close contacts,” said Regeneron’s chief scientific officer, George Yancopoulos. “The REGEN-COV antibody cocktail may be able to help break this chain by providing immediate passive immunity to those at high risk of infection, in contrast to active vaccines which take weeks to provide protection.”

Eli Lilly disclosed results from a study with its own two-drug cocktail regimen in high-risk patients recently diagnosed with COVID-19. Of 1,035 patients there were 11 hospitalisations or deaths in the treated patients versus 36 in the placebo group. No treated patients died, compared to 11 placebo patients. The trial data “add valuable clinical evidence about the role neutralizing antibodies can play in fighting this pandemic,” Lilly Chief Scientific Officer Dan Skovronsky, said in a statement. "The death toll from COVID-19 continues to rise around the world, and hospitalizations, particularly in the U.S., have reached record highs," he said. “These data further support our belief that bamlanivimab and etesevimab together have the potential to be an important treatment that significantly reduces hospitalizations and death in high-risk COVID-19 patients.”

Both studies underly the benefit of antibody therapy, but both drugs remain underutilised because of difficulty in administrating them. Antibody cocktails need to be administered through a several hours perfusion which can only be performed in appropriate centres. 

In another rare move, Eli Lilly, GlaxoSmithKline and Vir have announced a trio arrangement to test the combination of Eli Lilly’s bamlanivab with VIR-7831, a monoclonal antibody developed by Vir and GlaxoSmithKline. “With a virus like SARS-CoV-2, it’s expected that variants could emerge that require new therapeutic options, which is why Lilly is studying bamlanivimab together with other neutralising antibodies, including etesevimab,” “Adding VIR-7831 to our study is an important part of our commitment to develop therapies to treat current and future strains of COVID-19 until vaccines are widely available and utilised.” Dan Skovronsky said. The first patient has already be dosed and the BLAZE-4 clinical study aims at recruiting 1,000 subjects.

Paris, January 28, 2021

This document has been prepared by btobioinnovation and is provided to you for information purposes only.  The information contained in this document has been obtained from sources that btobioinnovation believes are reliable but btobioinnovation does not warrant that it is accurate or complete. The views presented in this document are those of btobioinnovation’s editor at the time of writing and are subject to change.  btobioinnovation has no obligation to update its opinions or the information in this document.