european end-to-end CDMO company, pharma services
LinkedIn Share

New RSV vaccines linked to rare neurological disorder

  • Preliminary data from the post-licensure studies of novel RSV vaccines point to an increased risk of Guillain-Barre syndrome (GBS), a serious neurological disorder. The attributable risk is estimated at 1 per 50,000 doses for Pfizer’s and <1 per 100,000 doses for GSK’s vaccine.
  • The two RSV vaccines were licensed last year to protect elderly and infants from severe lower respiratory tract infections. Millions of doses have been distributed since.
  • The vast benefits of RSV vaccination outweigh the small risk of Guillain-Barre syndrome and CDC will continue to recommend the vaccine for high-risk patients.

The newly licensed RSV vaccines (Abrysvo from Pfizer and Arexvy from GSK) may raise the risk of Guillain-Barre syndrome, according to the preliminary safety data unveiled recently by the CDC and FDA. Guillain-Barre syndrome is a rare, but serious neurological disorder, manifesting as a rapid-onset of muscle weakness and limb paralysis. It is an autoimmune condition involving the damage of peripheral nervous system by patient’s own immune system. Most patients recover within a few months, but a small number may experience permanent disability.

The researchers from CDC and FDA analyzed the data from three early detection databases that include spontaneously reported adverse events (VAERS), electronic health records (Vaccine Safety Datalink) and administrative claims (Medicare). All sources pointed to an increased risk with RSV vaccines. For example, the spontaneous reporting rate of Guillain-Barre syndrome within 21 days of vaccination with Abrysvo was 4.6 per million administered doses, whereas only 2 events were expected under the no-relationship scenario. In Medicare, the frequency of GBS was 6.9 times higher than anticipated for Pfizer vaccine and 2.8 times higher for GSK vaccine. The adjuvanted product developed by GSK seemed to have lower risk than the unadjuvanted vaccine from Pfizer, but this must be confirmed. The absolute risks remain small: around 1 per 50,000 doses for Abrysvo and less than 1 per 100,000 doses for Arexvy. Interestingly, isolated cases of Guillain-Barre syndrome have also encountered in the pre-licensure trials of both vaccines, but at that time no cause-effect relationship could be established. Despite the consistent findings from three independent sources, officials caution that the results are by no means conclusive and that additional studies are required to confirm the findings and calculate the exact frequency of post-vaccination GBS.

The two RSV vaccines were licensed in 2023 to fight one of the most important causes of lower respiratory tract infections among infants and elderly (see our previous article “Market welcomes the arrival of RSV vaccines”). In the United States, Abrysvo is registered for use in pregnant mothers at 32-36 weeks of gestation (for protecting the infants via passive antibody transfer) and adults aged 60 and older, while Arexvy is approved solely for the latter indication. In the pivotal clinical trials, their efficacy exceeded 80% for preventing severe RSV outcomes, giving hope to finally reduce the immense burden of RSV infections.

Despite the association with an undoubtedly severe and disabling condition, officials say that RSV vaccines continue to have a favorable benefit-risk ratio. According to the analysis performed by the CDC, vaccinating one million elderly individuals with GSK’s product would allow to prevent 23,000 doctor visits, 2,400 hospitalizations, 450 intensive care admissions and 120 in-hospital deaths over the 2 consecutive seasons. The same numbers for Pfizer’s vaccine are 26,000, 2,700, 520 and 140. This would come at a cost of 5 additional cases of GBS for Arexvy and 20 for Abrysvo. Based on these results, the CDC decided to maintain their recommendation to vaccinate the high-risk populations.

It is clear that even large-scale clinical trials enrolling more than 10,000 subjects are unable to pick up extremely rare adverse reactions such as Guillain-Barre syndrome. This can be achieved only after the product appears on the market and is administered to millions of patients. Fortunately, the authorities now possess several highly efficient tools for quick identification of safety signals, which allow them to promptly analyze the benefit-risk ratio and, if necessary, impose appropriate regulatory actions. In this case, it took only several months to detect the potential association between RSV vaccines and GBS, demonstrating the responsiveness of the current safety monitoring system.

No medication or vaccine is 100% safe and not all adverse reactions surface during the pre-licensure studies. What truly matters is the balance between benefits and risks, and in the context of RSV vaccines, the advantages of vaccination clearly win over the miniscule risk of serious side effects.

Prepared by:


Adam Tuszyner

References

  1. Lloyd, Patricia “Preliminary Analysis of Guillain-Barré Syndrome (GBS) following RSV Vaccination among adults 65 years and older.” Meeting of the Advisory Committee on Immunization Practices (ACIP) (February 29, 2024). Link: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/06-RSV-Adults-Lloyd–508.pdf.
  2. Shimabukuro, Tom “Post-licensure safety monitoring of respiratory syncytial virus (RSV) vaccines in adults aged ≥60 years.” Advisory Committee on Immunization Practices (ACIP) (February 29, 2024). Link: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/05-RSV-Adults-Shimabukuro-508.pdf.
  3. Melgar, Michael; Roper, Lauren “RSV Vaccination in Older Adults: Benefit-Risk Discussion.” Advisory Committee on Immunization Practices (ACIP) (February 29, 2024). Link: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/07-RSV-Adults-Melgar-508.pdf.
  4. Niazi, Sarfaraz. “Scientific rationale for waiving clinical efficacy testing of biosimilars.” Drug Design, Development and Therapy (2023): 2803-2815445.
  5. Kirsch-Stefan, Nadine, et al. “Do the outcomes of clinical efficacy trials matter in regulatory decision-making for biosimilars?.” BioDrugs 37.6 (2023): 855-871.
Share LinkedIn