Friday Five – The pharma week in review (27 November 2020)

And then there were three

For a third successive week, new promising data for a potential COVID-19 vaccine were announced by AstraZeneca and the University of Oxford on Monday. Though on this occasion, the results have raised far more questions than provided answers.

This vaccine, which uses a novel chimpanzee viral vector, does not appear to be as effective as the mRNA-based vaccines being developed by partners BioNTech and Pfizer, and Moderna, both of which have demonstrated effectiveness rates of 95% in large Phase III studies carried out in the US.

By comparison, two full doses of AZD1222 were shown to be 62% effective based on data taken from two Phase II/III studies that are taking place in the UK and Brazil.

However, no severe cases of COVID-19 or hospitalisation occurred in patients who received the vaccine. Furthermore, AZD1222 can be produced at a significantly larger scale more quickly and can be easily stored for long periods at refrigeration temperatures. In short, it is a much easier vaccine to manufacture and distribute and could still prove highly useful in helping to end the pandemic, particularly in less developed parts of the world.

AZD1222 was also shown to be 90% effective in a small cohort of patients who by error received only a half dose of the vaccine initially, with investigators also suggesting they have preliminary evidence for the prevention of asymptomatic infection. It is entirely plausible, one expert told FirstWord, that a smaller initial dose will more effectively prime the immune system. However, based on the small number of people who received this dosing regimen it is also possible that this higher efficacy rate occurred by chance. Reports also indicate that only patients aged 55 and under received this regimen.

AstraZeneca said it was confident in the data, which will quickly be discussed with regulators, but over the course of the week has come under increased scrutiny about how the release of these results was handled, including its assertion that across both dosing regimens AZD1222 had shown an 'average' effectiveness rate of 70%.

It must be hoped that these issues can be quickly resolved. AstraZeneca said on Thursday it will run a new Phase III study to evaluate the half-dose/full-dose regimen and is hopeful the required data can be generated quickly. How regulators assess available results in the meantime, however, remains to be seen.      

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Other COVID-19 vaccine news of note

If subsequent data does confirm AZD1222 to be a less effective vaccine, it will raise questions about where it is approved and how it is used. Particularly as AstraZeneca and the University of Oxford have pledged to provide it at cost-price for the duration of the pandemic and governments around the world have leaned heavily on AZD1222 when securing pre-orders of multiple vaccine candidates.

Our short survey of 118 infectious disease specialists, which was fielded just ahead of new data for AZD1222 being disclosed, suggests that the 95% effectiveness rates demonstrated by BioNTech and Pfizer's BNT162b2 and Moderna's mRNA-1273 have raised the bar for subsequent candidates for some.

Sixty-nine (69) percent of respondents said they would consider using a less effective COVID-19 vaccine with a similar side-effect profile if their access to the most effective vaccines was limited. However, following the release of initial data for the two first mRNA vaccines, a quarter of all respondents said they would no longer be comfortable using a vaccine with lower efficacy; a trend more pronounced among US respondents, 30% of whom feel this way.

Those willing to use a vaccine with lower efficacy suggest on average they would be comfortable with one demonstrating efficacy of around 77% or above, showing just how high the bar has risen. 

Illustrating how the vaccination landscape may evolve, European Commission President Ursula von der Leyen on Tuesday confirmed this week that the EU will approve a new contract to buy up to 160 million doses of Moderna's mRNA-1273.

Elsewhere, a new update from a Phase III study of the Gamaleya Institute's COVID-19 vaccine Sputnik V suggests that it has an efficacy rate of 91.4% as measured seven days after administration of the second dose, the Russian Direct Investment Fund (RDIF) announced Tuesday. The second interim analysis of the trial was performed after 39 confirmed cases of coronavirus, with 31 cases in the placebo group versus eight cases in those who received Sputnik V.

Some scepticism towards these data will remain, certainly until more case numbers accumulate, though the fact that Sputnik V utilises two distinct viral vectors for the first and second doses makes for interesting comparison with AstraZeneca's findings.

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Novartis in the spotlight

At an investor event this week, Novartis provided a comprehensive review of its business and growth outlook, including an overview of a suite of emerging high-risk, high-return 'wildcard' assets in its R&D pipeline.

We took a closer look here at five key themes that emerged from the presentations, including why Novartis may beat its own sales forecasts for the new multiple sclerosis treatment Kesimpta and its breast cancer drug Kisqali, and how a new oncology project focusing on SHP2, a protein that could be targeted to help overcome resistance to existing cancer treatments, may help the company get ahead of the competition in this therapy area. 

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More momentum for RNAi

One area where Novartis hopes to show continued progress is in the field of RNAi and it is awaiting imminent approval of its first drug that uses this technology, the investigational cholesterol reduction therapy inclisiran. Novartis spent $9.7 billion to acquire The Medicines Company and gain access to inclisiran a year ago.

Many analysts remain sceptical that inclisiran will generate sufficient revenues to justify the cost of the acquisition; we are surveying cardiologists ahead of potential approval to gauge prescriber anticipation and will publish results next week. However, Novartis believes that the acquisition of The Medicines Company brings other key benefits, such as the largest RNAi manufacturing capacity in the industry, which will emerge over time. Its focus on future RNAi therapies will be liver diseases, the company said on Tuesday.

Elsewhere, Alnylam Pharmaceuticals secured both European and US approval for its third RNAi product this week – the primary hyperoxaluria type 1 therapy Oxlumo – just as the modality approaches an inflection point for broader uptake across cardiovascular and metabolic diseases. Analysis here.

While inclisiran will be the test case for RNAi outside of the rare disease setting, it's far from the only contender vying for a piece of a larger pie. Amgen recently highlighted its partnership with Arrowhead Pharmaceuticals to develop AMG 890, an RNAi targeting ARO-LPA now in a Phase II study to treat elevations in Lp(a), which are associated with an increased risk of cardiovascular disease.

AstraZeneca recently in-licensed a second RNAi candidate from Ionis Pharmaceuticals for the treatment of non-alcoholic steatohepatitis (NASH). Having already put IONS839 (also known as AZD2693) into a Phase I study, AstraZeneca will now be responsible for the development of ION455. A third candidate wholly owned by Ionis, IONS224, is also in development for NASH.

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Deals round-up

BMS enters drug-development deal with Schrödinger

Lilly partners with Precision BioSciences on genome-editing therapies

Merck & Co. adds to COVID-19 pipeline via purchase of OncoImmune

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