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

Malaria monoclonal antibody protects against controlled infection

10th August 2022

A malaria monoclonal antibody in a phase 1 trial has been found to provide protection against controlled infection in the majority of patients

A malaria monoclonal antibody provides protection against controlled infection in virtually all patients according to the findings of a phase 1 clinical trial by a US research team.

Malaria is an acute, febrile illness caused by Plasmodium falciparum (P. falciparum), a unicellular protozoan parasite, spread through the bites of infected female Anopheles mosquitoes. It is an extremely common disease and the World Health Organisation has estimated that in 2020 there were 241 million cases of malaria, leading to an estimated 627,000 deaths. While there have been huge efforts directed towards the development of a vaccine, the available data suggests that the RTS,S/AS01 candidate malaria vaccine, has an efficacy of only 36.6%. Some research has shown how antibodies can prevent malaria by neutralising sporozoites (i.e., the infectious form of Plasmodium deposited into the skin when a mosquito bites) before they infect hepatocytes in the liver  A recognised antibody target is the P. falciparum circumsporozoite protein, that is required for parasite motility and invasion of hepatocytes and in a 2021 study, it was shown that a malaria monoclonal antibody, CIS43LS, which targets this protein, prevented malaria after controlled infection. For the current phase 1 trial, researchers modified the CIS43LS monoclonal antibody to create a more potent agent, L9LS and described its safety, pharmacokinetics and protective efficacy in health adults who had never been infected with malaria or received a vaccine.

Study participants were given either intravenous LSL9 at doses of 1, 5 and 20 mg/kg or a subcutaneous dose of 5 mg/kg, whereas some did not receive the monoclonal antibody and served as controls. Within 2 to 6 weeks after administration of LSL9, participants were exposed to bites on the forearm from the Anopheles stephensi mosquito which had been infected with P. falciparum. Parasitaemia (i.e., the detection of parasites in the blood) was assessed after 21 days using a PCR test and for the purposes of the study, participants were considered to be protected by LSL9, if parasitaemia did not develop at this point in time. In cases where parasitaemia did occur, individuals were treated with 1 gm atovaquone and 400 mg of proguanil for 3 days.

Malaria monoclonal antibody and parasitaemia

A total of 27 participants were enrolled with a mean age of 24.5 years (50.3% female), 18 of whom received L9LS (and 9 serving as controls) with 5 receiving the drug subcutaneously. Controlled infection was administered to 23 participants (17 given L9LS and 6 controls).

The results showed the L9LS had dose linearity with the highest mean serum concentration of 914.2 mcg/ml from the 20 mg/kg intravenous dose and the estimated overall clearance was 46.1 ml/day with a half-life of 56 days.

Parasitaemia developed in 2 of the 17 participants given L9LS and all 6 controls (p < 0.001) and did not develop in those given 5 or 20 mg of intravenous L9LS. Interestingly, protection was afforded by serum concentrations of L9LS as low as 9.2 mcg/ml.

The authors concluded that these results indicated that prevention of malaria could be achieved after a single dose of L9LS and that further studies were needed to examine the value of the drug among infants and children.

Citation
Wu RL et al. Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria N Eng J Med 2022

Third booster sera samples have reduced neutralisation against Omicron COVID-19 variant

22nd December 2021

Third booster sera samples have been found to produce a four- six-fold decrease in neutralisation when tested against the Omicron variant

In a laboratory-based study, third booster sera samples from patients have been shown to produce a four to six-fold reduction in neutralisation against the Omicron COVID-19 variant. This was the finding of a preprint study by researchers from the Aaron Diamond AIDS Research Center, New York, US.

The Omicron COVID-19 variant (B.1.1.529) was first identified in southern Africa and appears to have a high level of transmissibility and will likely cause outbreaks across the globe. A concern with this particular variant is that it contains more than 30 mutations,15 of which are present in the receptor-binding domain region which is the target for neutralising antibodies produced in response to vaccination. It is therefore possible that the Omicron might lead to an increased level of infection despite vaccination although current opinion is that this could be mitigated by a third booster sera sample.

In the absence of clinical data, the US team sought to better understand the extent to which the Omicron variant is able to evade antibody neutralisation, by testing the activity of serum collected from a number of different patient samples. Initially the team created an Omicron pseudovirus and tested this against 10 sera samples collected from the Spring of 2020, which were likely to have been infected with the wild-type (original) COVID-19 virus. While there was a robust response to the wild-type, there was a greater than 32-fold reduction against Omicron and only two samples produced antibody titres above the limit of detection.

Vaccinated samples

The team then turned their attention to both fully vaccinated and third booster sera (TBS) samples. For the two mRNA-based vaccines, BNT162b2 and mRNA-1273, there was a >21-fold decrease in ID50 and > 8.6-fold decrease in boosted sera samples. For the other vaccines, Ad26.COV2.S and ChAdOx1, all samples produced antibody titres below the limit of detection apart from two samples for which the individual had a history of a prior infection.

Using 15 third booster sera samples obtained from BNT162b2 (13) and mRNA-1273, the researchers discovered that although each of these third booster sera produced antibody titres above the limit, there was a mean 6.5-fold drop compared to the wild-type.

Using authenticated Omicron isolates and samples from BNT162b2 and mRNA-1273, there was a greater than 6-fold drop in titres for fully vaccinated and a greater than 4.1-fold drop for boosted samples.

Finally, testing sera with monoclonal antibodies, the researchers found that all four combinations of monoclonal antibodies in clinical use lost substantial activity against Omicron.

Although this was a laboratory-based study and might not be replicated in clinical practice, the authors believed that COVID-19 is potentially only a mutation or two away from being resistant to current antibodies and that it was important to devise strategies that anticipate the evolutional direction of the virus and that future work should focus on the development of agents targeting conserved parts of the virus.

Citation

Liu L et al. Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2 BioRxiv 2021

Regdanvimab recommended as a treatment for COVID-19 by the CHMP

12th November 2021

The CHMP has issued a positive scientific opinion recommending marketing authorisation for regdanvimab (CT-P59), a monoclonal antibody treatment for adults with COVID-19 who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.

The CHMP positive opinion for regdanvimab marks the first time a monoclonal antibody treatment for COVID-19 has received a recommendation for marketing authorisation from the European Medicines Agency (EMA). 

The positive CHMP opinion was supported by data from the global Phase III clinical trial in which Celltrion enrolled more than 1315 people to evaluate the efficacy and safety of regdanvimab in 13 countries including the US, Spain, and Romania. Data showed regdanvimab significantly reduced the risk of COVID-19 related hospitalisation or death by 72% for patients at high-risk of progressing to severe COVID-19.

Rolling review of regdanvimab had been initiated by the EMA in February 2021 and the announcement of the CHMP positive opinion for regdanvimab follows the submission of a marketing authorisation application to the EMA seeking approval of regdanvimab in October 2021.

“The primary benefits of monoclonal antibodies are their high specificity and safety – they are highly specific for a single target, so these monoclonal antibodies rarely cause undesirable side effects,” said Oana Sandulescu, MD, PhD, Associate Professor of Infectious Diseases at the Carol Davila University of Medicine and Pharmacy in Romania. “An infusion of an hour of monoclonal antibodies like regdanvimab can ease COVID-19 symptoms and reduce complications in recently diagnosed, non-hospitalised people at high risk, and thus plays an important role in preventing further spread of the virus.”