Disease Analysis: COVID-19 Prevention

Definition

COVID-19 is an infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that emerged in late 2019 in Wuhan, China. As of October 2021, there have been 245,373,039 confirmed cases of COVID-19, and 4,979,421 deaths globally. SARS-CoV-2 belongs to the coronavirus family, which collectively cause respiratory and intestinal disease in humans and animals, with other prominent members of the family including Middle East respiratory syndrome (MERS) virus and severe acute respiratory syndrome (SARS) virus

Latest key takeaways

• Several vaccines have been approved for emergency use in adults across the world, and while estimates of efficacy against symptomatic COVID-19 have varied from 50% to 95%, efficacy estimates against severe infection/hospitalization have been consistently high across all vaccine approaches investigated thus far. However, the emergence of the Omicron variant, the first variant to show meaningful immune evasion, led to a substantial reduction in vaccine efficacy. A third booster dose largely restores efficacy, which is an important finding as severe/hospitalized COVID-19 infections represent the greatest social and economic disease burden, and the primary aim of current vaccination campaigns is to reduce mortality and ease pressure on overwhelmed hospitals by reducing hospitalization rates.
• Efficacy against asymptomatic infection is an important factor that could serve to differentiate the various vaccine approaches in the long term, as asymptomatic carriers are believed to be responsible for approximately one quarter of transmissions, thus vaccines capable of inducing sterilizing immunity will also provide some measure of indirect protection to non-vaccinated individuals. Earlier-launched vaccines developed by Pfizer/BioNTech, Moderna, and AstraZeneca have benefited from real-world evidence against the Alpha and Delta variants showing that they have substantially cut asymptomatic transmission. Though current vaccines are unlikely to show efficacy against asymptomatic disease caused by the Omicron variant, such protection may be a key differentiator for future, variant-specific vaccines.
• Given the constant threat of the emergence of new viral variants bearing mutations in the spike protein that allow them to partially or fully evade immune responses generated by first-generation vaccines, developers that can generate data showing efficacy against current and future variants will have a substantial advantage, though the extent of the advantage will depend on the prevalence and spread of the variants in each region. With the Omicron variant now the dominant strain globally, accounting for >95% of new cases in the US and Europe, efficacy against this strain is paramount to long-term commercial potential. So far, Pfizer and BioNTech’s Comirnaty and Moderna’s Spikevax have shown the most robust efficacy data against the Omicron variant with vaccine efficacy of ~90% against hospitalization and death after a third booster dose, though protection wanes considerably after four months.
• Vaccine supply and pricing will also be crucial determinants of uptake, with the former likely to be the dominant influencer of market share trends throughout H1 2022 as demand outstrips supply. Conversely, pricing will become a more prominent factor after the pandemic phase as supply constraints are resolved and companies seek to adopt more typical vaccine pricing to ensure longer-term profitability. Johnson & Johnson was the first not-for-profit vaccine manufacturer to detail plans of transitioning its COVID-19 vaccine to a more typical commercial product. However, earlier pledges from Johnson & Johnson and AstraZeneca to market vaccines at non-profit prices during the pandemic phase could set a price ceiling that may be hard to escape from beyond 2022, particularly given that competition from additional manufacturers is expected by that point. Indeed, even if only the current late-phase vaccines successfully reach the market, there will be substantial oversupply of vaccines post-2022, thus Datamonitor Healthcare expects significant pipeline attrition in the near term and possible market withdrawals post-2022 as more minor players reallocate resources to other, more profitable indications. Pipeline attrition was evidenced by Sanofi’s recent decision to abandon development of its mRNA vaccine, with the company stating that it was unable to compete with the dominance of Comirnaty and Spikevax.
• Demand is expected to outstrip supply until at least mid-2022, meaning additional market entrants are still required to increase vaccine availability. This is especially the case for lower-income markets, which have struggled to compete in securing priority access to vaccines compared to developed markets. Fortunately, several more vaccines are expected to launch throughout 2022 which will substantially boost global supply. The COVAX initiative (coordinated by the Coalition for Epidemic Preparedness Innovation [CEPI], the vaccine alliance GAVI, and the World Health Organization [WHO]) will also play a pivotal role in ensuring lower-income markets are able to have access to vaccines, though this supply will only be sufficient to vaccinate the highest-risk groups rather than entire populations. Although supply to COVAX fell short throughout 2021, the easing of restrictions on vaccine exports in India, the scale-up of manufacture for AstraZeneca’s and Johnson & Johnson’s vaccines, and the approvals of multiple additional vaccines by the WHO will substantially increase supply throughout 2022.
• Inactivated vaccines have played a crucial role in primary vaccination series in China, India, Russia, and other emerging markets. However, as domestically produced vectored, protein subunit, and eventually mRNA vaccines reach emerging markets, inactivated vaccines are expected to progressively lose market share. Moreover, these vaccines are unlikely to gain approval in the US and EU given that regulators will be reluctant to approve vaccines with inferior efficacy. Inactivated vaccines have the advantage of long shelf-lives and therefore may play a role in stockpiles which will be needed to curb breakthrough infections as new variants emerge.
• Comirnaty’s and Spikevax’s excellent efficacy and safety profiles and first-to-market statuses have positioned them for phenomenal sales potential in 2022, with Pfizer achieving $36.8bn, BioNTech $17bn, and Moderna $18.5bn in sales in 2021. Comirnaty’s greater success thus far likely reflects Pfizer’s extensive commercial resources and marketing experience, as well as its higher manufacturing capacity (annual capacity of 3 billion doses in 2021 vs 800 million to 1 billion for Moderna), which has allowed the company to secure more pre-purchase agreements, including deals with the EU totaling 2.4 billion doses.
• Comirnaty will benefit from having a cleaner safety profile compared to rival vaccines, especially since Spikevax has recently been associated with a higher risk of heart inflammation. The risk of heart inflammation in younger populations has led to delays in the approval of Spikevax for adolescents aged 12–17 years and children aged 5–11 years in the US. Additionally, Swedish and Danish healthcare agencies have paused the use of Spikevax in younger age groups, opting to use Comirnaty instead. A superior safety profile will allow Comirnaty access to younger age groups, with the FDA requesting that the company pursues development for very young children <5 years of age.
• The longer-term role of adenoviral vector-based vaccines is in doubt following the association of AstraZeneca’s and Johnson & Johnson’s vaccines with an increased risk of very rare blood clots, including cerebral venous sinus thromboses that also present with thrombocytopenia, and Guillain-Barré syndrome. It is currently unclear if these adverse events are a class-wide effect, as similar events have not yet been reported with Russia’s Sputnik V (Ad26 and Ad5) or CanSino’s Convidecia (Ad5), but widespread media coverage of blood clots, in particular with AstraZeneca’s Vaxzevria and Johnson & Johnson’s JNJ-78436735, has led to significant hesitancy among younger adults, particularly younger women.
• Vaccines will ultimately be able to cater for the vast majority of individuals, but there remains a significant market opportunity for monoclonal antibodies and antivirals in the prevention setting for those who are not eligible for vaccination or who require immediate protection in outbreak control settings. GlaxoSmithKline’s Xevudy (sotrovimab) is expected to become the lead monoclonal antibody therapy for the prevention of severe COVID-19, since Regeneron Pharmaceuticals’ REGEN-COV (casirivimab + imdevimab) and Eli Lilly’s bamlanivimab + etesevimab have failed to show strong efficacy against the Omicron variant. Eli Lilly’s next-generation monoclonal antibody cocktail bebtelovimab was recently approved and is expected to present strong competition to Xevudy. Post-exposure prophylaxis trials for Xevudy have been delayed to H2 2022, therefore the drug is unlikely to gain a label expansion to post-exposure prophylaxis until 2023. AstraZeneca’s Evusheld is the only marketed pre-exposure prophylaxis treatment available in the US (since December 2021); however, given its high cost the treatment is likely to be reserved for immunosuppressed individuals. Nonetheless, AstraZeneca has secured hefty deals (worth >$1bn) with the US government to supply 1.7 million doses of Evusheld throughout 2022.
• Key upcoming catalysts include final results from pivotal trials of Sanofi/GlaxoSmithKline’s vaccine, and regulatory decisions for Novavax’s NVX-CoV2373, Johnson & Johnson’s JNJ-78436735, and REGEN-COV.