Vaccines breakthroughs call for cautious optimism

By Ameen Kamal, Head of Science & Technology at EMIR Research,

News of a vaccine breakthrough from Pfizer Inc. and BioNTech SE on its mRNA-type BNT162b2 vaccine achieving 90% effectiveness have stirred positive reactions as many see this as a significant light at the end of the tunnel. The pandemic has hit the economy very severely and people (and the market) deserve this ray of hope.

Russia’s Sputnik V vaccine by Gamaleya Research Institute followed suit claiming a staggering 92% effectiveness. It’s reasonable to assume that the timing of Sputnik V press release came as response to Pfizer-BioNTech’s announcement. As Malaysia is reportedly prepping to make advanced purchase of vaccines, the public or even geopolitical sentiments – no matter how significant it may seem – must not influence a populist, or sentiment-driven decision-making for policy makers.

Claims of 90% or 92% effectiveness are really good given the 50% efficacy bar by the U.S. Food and Drug Administration (USFDA). As mentioned by Matthew Herper, Senior Writer for Medicine at STAT – a US-based health news site – expert projections of Covid-19 vaccine effectiveness was around 60% – 70%. Therefore, these claimed efficacies are better than what most had expected.

However, the efficacy rate may change for both vaccines as the respective clinical trials continue. Referring to Pfizer-BioNTech vaccine, health and science correspondent James Gallagher mentioned the absence of full clinical trial results which have yet to be published in medical journals to be peer-reviewed – which could also be the case with Sputnik V according to its press release.

Gallagher raised a similar concern as EMIR Research by alluding to immunity retainment as the ‘biggest question’, and that it may take a long time to be elucidated. High-efficacy vaccines can still be undermined by short retainment of immunity – complicating vaccination efforts, and further pressuring the already-stretched supply chains for new batches faster than expected. Chinese authorities have reportedly lowered the immunity retainment bar to 6 months.

Immunity retainment, any potential long-term side effects, and long-term safety of novel adjuvants (vaccine mixture compounds), if any, need a longer time to be determined. The Sputnik V press release alludes to the ability to provide “long-term immune response after the second injection”. Pfizer is perhaps more prudent to not make such claims yet, and mentioned that participants will continue to be monitored for an additional two years after the second dose, while the Sputnik V press release indicated only six months.

It is worth noting however, that unlike Pfizer-BioNTech vaccine, Sputnik V has been given emergency use ‘authorisation mechanism’ to allow it to be administered to high-risk groups. Success would confer a real-world data advantage over competitors, despite being an arguably risky move.

If Malaysia would call for emergency use of such vaccines – and therefore taking a higher risk than in normal circumstances – it is imperative to also conduct a similar monitoring on the Malaysia population to determine parameters such as immunity retainment, safety, efficacy, and efficiency.

It is also important to note that the unprecedented speed by which vaccines are being developed. The pandemic hasn’t even reached one year, and already we have vaccines in Phase 3 clinical trials with above 90% effectiveness, and with both vaccines claiming no serious safety or adverse concerns thus far.

Understandably, there may be a concern that lucrative market prospects and geopolitics may pressure any parties to cut corners. Therefore, thorough assessment by local authorities is crucial despite pressures of socio-economy and geopolitics.

According to World Economic Forum senior writer Douglas Broom, vaccine discovery to approval, in general, can take about ten years. This is attributed to the nature of the entire scientific process that is naturally time consuming, resource intensive, and is subject to stringent requirements set by regulatory bodies for approval.

Vaccine development is also plagued with high failure rate – about 93% of vaccine candidates fail from the stage of animal testing to successful vaccine registration, as mentioned by Jerome Kim, director-general of the International Vaccine Institute when speaking to CNBC.

New technologies and vast resources have undoubtedly sped up the process, but the fact is that mRNA vaccines are novel, never approved before and haven’t been tested for very long. On the other hand, Sputnik V vaccine is claimed to be “based on a well-studied human adenoviral vector platform that had proven safe and effective with no long-term side effects”. Nevertheless, cautious optimism is reasonable for both.

Also, how much of the demographics tested in the clinical trials of both vaccines are relevant, and therefore, can be extrapolated to Malaysia population?

Long-term effects for novel mRNA vaccines are relatively a much bigger unknown as this is not yet sufficiently established in the Pfizer-BioNTech Phase 3 trials that started on July 27. Proponents of Sputnik V appears to tout the “well-studied human adenoviral vector platform”, alluding to higher levels technology familiarity, track record, and therefore, safety. Needless to say, this has to be backed up with full trial reports and longer tests.

In any case, EMIR Research noted previously that these metrices and uncertainties are likely to be reflected in prices and various legal wordings in contracts, especially ‘advanced purchase’ ones. So Malaysian authorities must review these carefully, regardless of public sentiment.

Relatedly, Malaysia also has no experience for production and related supply chain experience for any Covid-19 vaccine candidates, as it would have if Malaysia participated in producing doses needed for clinical trials. Understandably, the concern may be higher for the more novel types of vaccines such as BNT162b2 by Pfizer-BioNTech.

As for logistical challenges, EMIR Research has previously highlighted that according to Fierce Pharma associate editor Kyle Blankenship, BNT162b2 was reportedly requiring temperatures of -70 degrees Celsius for longer-term storage and at refrigerated temperatures for up to two days.

Such operating parameters may limit vaccination to be conducted at sites with specialised equipment, by trained personnel and for a very limited duration per vaccination event.

Gallagher opined similarly by mentioning “massive manufacturing and logistical challenges in immunising huge numbers of people, as the vaccine has to be kept in ultra-cold storage at – 80Cº”. According to Herper, Pfizer is confident in the manageability of these issues.

Should this vaccine be one of Malaysia’s choice, the country requires ultra-cold chains in handling the movement and storage of such vaccines and properly trained personnel – especially in nation-wide vaccination efforts. As reported by Reuters, this may present a significant challenge for regions where a combination of high temperatures and insufficient infrastructure (such as in Asia) can make it difficult to maintain the cold chain when moving vaccines.

Comparatively, Blankenship mentioned Moderna – another company pursuing mRNA vaccine – as reportedly requiring -20 degrees Celcius for storage and if so, may confer a logistical advantage. This could be similar to Sputnik V’s “no higher than -18 degrees Celcius” storage requirement as alluded to by author Kostadin Fikiin in a Euractive article. Blankenship also mentioned other types of vaccines by other companies that may be held for months at refrigerated temperatures.

Accordingly, it’s reasonable to assume that specialised equipment and a higher-level of care would be needed in handling fill-and-finish for the more temperature-sensitive types. Whichever is Malaysia’s decision, this must be addressed early-on.

More results are expected by the end of this year and probably in the first quarter of 2021, which should provide more insights on the performance of these vaccines. Therefore, before putting all bets on one vaccine, thorough comparative assessment between different vaccines should be conducted.

Nevertheless, findings thus far from Pfizer-BioNTech and Gamaleya Research Institute’s Sputnik V vaccine appear to be big wins for science, a much-needed hope for the people and is a cause for applause – but with cautious optimism, and not yet to shoot fireworks.