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Press Releases

Take a look at a selection of our recent media coverage:

Resistance mutations develop in Omicron sub-variant patients treated with sotrovimab

5th August 2022

Resistance mutations in the Omicron sub-variants quickly develop in patients treated with sotrovimab, thereby delaying the time to viral clearance

Resistance mutations have been found to develop after a few days treatment with sotrovimab in patients infected with Omicron sub-variants and which significantly delays the time to viral clearance. This was the conclusion of a small study by researchers from the University of Amsterdam.

Sotrovimab is an human monoclonal antibody that targets a highly conserved epitope in the COVID-19 spike protein at a region that does not compete with binding of the angiotensin-converting enzyme 2. The monoclonal antibody has been approved by the EMA to treat confirmed COVID-19 in adults and adolescents who do not require supplemental oxygen therapy and who are at risk of progressing to severe COVID-19. However, there is a concern over the development of resistance mutations in monoclonal antibodies and this has already been observed with sotrovimab in patients infected with the delta variant. Sotrovimab is one of the few monoclonal antibodies that retains efficacy against the widely circulating Omicron BA.1 sub-lineage although whether resistance mutations can still develop in those infected with the omicron variant and its sub-variants is unclear.

In the present study, the Dutch team examined whether resistance mutations could develop during therapy with sotrovimab in patients infected with Omicron. A single 500mg dose of the drug was administered to a group of ambulatory, hospitalised, high-risk patients with COVID-19 and nasopharyngeal specimens were collected on days 0, 7 and 28 and subjected to whole-genome sequencing. For the primary outcome, the Dutch team set the emergence of spike protein resistance-associated mutations at positions E340 or P337 during treatment with sotrovimab as the primary outcome. The team used a Cox proportional hazard model to estimate the time to viral clearance with resistance mutations as a covariate.

Resistance mutations and outcomes

A total of 47 high-risk patients were studied but only 18 had more than one nasopharyngeal specimen taken and included in the final analysis. The remaining patients either declined or could not be contacted. For the final cohort, the mean age was 60.9 years (50% female) and 15 were immunocompromised due to either immunosuppressive conditions or treatments. All of the patients were given sotrovimab between 0 and 23 days after a positive PCR test for COVID-19.

Genomic analysis revealed that all patients were infected with the omicron variant, 17 with BA.1 and the remaining patient BA.2. Overall, 10 patients (56%) developed resistance mutations at spike position E340 or P337 within 3 to 31 days after treatment. Four patients developed resistance mutations to E340, all of whom were immunocompromised. Furthermore, mutations developed quickly with more than 50% having arisen between days 5 and 28. In comparison to those without mutations, the time to viral clearance was significantly longer (32 vs 19.6 days), giving a hazard ratio of 0.11 (95% CI 0.02 – 0.60) in patients displaying resistance mutations.

While accepting the study was based on a small number of patients and that they did to include clinical outcomes for resistant patients, the authors called for further studies to investigate the value of combination monoclonal antibody therapy combined with genomic sequencing for immunocompromised patients.

Citation
Birnie E et al. Development of Resistance-Associated Mutations After Sotrovimab Administration in High-risk Individuals Infected With the SARS-CoV-2 Omicron Variant JAMA 2022


Bivalent Moderna vaccine likely to protect against Omicron sub-variants

26th June 2022

A bivalent Moderna vaccine was found to produce a potent neutralising antibody response against two Omicron sub-variants BA.4 and BA.5

According to a press release a bivalent Moderna vaccine is able to generate a large neutralising antibody response against two of the Omicron sub-variants, BA.4 and BA.5 and therefore likely to protect against these variants.

Both the BA.4 and BA.5 sub-variants of Omicron were detected in South Africa in January and February 2022, respectively. Moreover, there have recently been concerns raised over these two sub-variants especially after a study published in the New England Journal of Medicine, found that the sub-variants, substantially escaped neutralising antibodies induced by both vaccination and infection. The results of the study showed that among individuals who had received a third (i.e., booster) dose of BNT162b, compared with the response against the original COVID-19 isolate, the neutralising antibody titre was lower by a factor of 21 against BA.4 or BA.5. In other words, it appears highly likely that even among those who have been fully vaccinated, the BA.4 and BA.5 can lead to re-infection.

The bivalent Moderna vaccine has been studied in a phase 2 and phase 3 trial which has yet to be published. In the study, all participants who had previously received 2 or 3 doses of an approved COVID-19 vaccine were then given mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the 4th dose.

Bivalent Moderna vaccine and Omicron sub-variants

According to the press release, for the COVID booster candidate, mRNA-1273.214, only one month after administration in previously boosted participants, a 50 µg booster dose elicited potent neutralising antibody responses against the Omicron sub-variants BA.4 and BA.5 in all participants. In fact, mRNA-1273.214 was able to increase the level of neutralising antibody titres against BA.4/BA.5 by 5.4-fold (95% CI 5.0 – 5.9) above baseline in all participants regardless of prior infection and by 6.3-fold (95% CI 5.7 – 6.9) in the subset of seronegative participants.

These results follow on from the data in a press release in early June 2022, in which Moderna announced that a booster dose with mRNA-1273.214 increased neutralising geometric mean titres (GMT) against the Omicron variant by approximately 8-fold above baseline levels. Moreover, a 50 μg booster dose of mRNA-1273.214 was well-tolerated in the 437 study participants and both the safety and reactogenicity profile of mRNA-1273.214 was similar to that of mRNA-1273 when these vaccines were administered as a second booster dose.

Based on these preliminary findings, Moderna is now working hard to complete all the necessary regulatory submissions in the coming weeks requesting to update the composition of the booster vaccine to mRNA-1273.214.