The Current State of SARS-CoV-2 Antibody Trials for COVID-19

This week I wanted to discuss the exciting and quickly evolving landscape of SARS-CoV-2 antibody trials for treating COVID-19. As always, this information is constantly changing and reflects the status of trials at the timing of writing.

Antibody therapy is an extremely promising horizon in the COVID-19 pandemic. By supplementing patients with antibodies specific to SARS-CoV-2, the therapy works by augmenting and supporting the immune system by helping to “mark” the virus. These antibodies can also single-handedly neutralize the virus. 

However, creating antibodies specific to a new virus is not an easy task with only one virus-targeting monoclonal antibody holding FDA approval to date (it’s Palivizumab in case you were wondering). The fastest method to collect these specific antibodies against a pathogen is to use serum from recovered patients. These recovered patients maintain moderate to high titers of virus-specific antibodies in the course of overcoming their infection. The plasma of these patients contains antibodies and is called convalescent plasma which is currently being supplemented to COVID-19 patients in multiple clinical trials. However, in using this plasma, patients also receive other antibodies from the donor that are against different pathogens or antigens. Thus, interestingly, the therapy as a whole is not specific to the SARS-CoV-2 virus.

Since antibody titers drop over time and recovered donors can only provide so much plasma, convalescent plasma is not a long term solution. Ultimately, the goal of antibody therapies in COVID-19 is to isolate and replicate antibodies specific to SARS-CoV-2 and supplement these manufactured antibodies to patients. The latter approach resolves the two main issues of convalescent plasma: non-specificity and volume availability. However, these specific and manufactured antibody therapies take a long time to develop and test. 

As shown in Table 1, there are currently six large antibody trials underway (convalescent plasma trials or antibodies not in clinical trials were excluded). Most of these trials use monoclonal antibodies (mAb) or a cocktail (mixture) of multiple mAbs. A mAb is a single highly specific antibody that was developed for a specific target.

The ACTIV-2 trial was recently announced and will use Lily’s LY-CoV555 antibody which was isolated and reproduced from a recovered COVID-19 patient. This trial is unique as it will focus on using this therapy in mild and moderate cases that don’t require hospitalization (outpatients) to test if antibody therapy will reduce the risk of escalation of severity. In tandem with the ACTIV-2 trial, the ACTIV-3 trial will use the same LY-CoV555 antibody but in hospitalized patients (inpatients). 

The Regn-CoV-2 is a double mAb cocktail developed by Regeneron pharmaceuticals and joined as a part of operation warp speed in July. This therapy’s two antibodies are specific against the Receptor Binding Domain (RBD) of the SAR-CoV-2 virus. The RBD region is part of the Spike (S) protein and is key in viral entry. By targeting this region, Regeneron hopes to better neutralize the virus by attacking a critical protein to viral propagation. Currently, Regeneron is testing their antibody cocktail in inpatients, outpatients, and household contacts of COVID-19 patients (Table 1). 

Out of South Korea, Celltrion has developed its mAb: CT-P59. CT-P59 is currently in phase I trials in South Korea with Celltrion having approval from both the UK’s Medicines and Healthcare products Regulatory Agency and Korea’s Ministry of Food and Drug Safety (MFDS). Moving forward Celltrion is hoping to test the antibody in mild and moderate COVID-19 patients in their phase II and III trials later this year. They are also hoping to begin phase I trials in Europe (starting with the UK) in addition to their local trials.

Tychan is also currently testing its mAB, TY207, in phase I trials. Out of Singapore, Tychan has also developed a mAb against the spike protein. Not many details are known about their future plans, but having started phase I trials in June they are hoping to have results and enter later phases by the end of the year.

In a collaboration between Junshi Biosciences and Eli Lilly they have begun phase I testing with Junshi’s JS016 mAb. Junshi has led development of the mAb out of China with Lilly acquiring the rights for the rest of the world. JS015 like many mAb for COVID-19 also targets the spike protein, but at a different epitope from Eli Lill’y other mAb LY-CoV555. If it shows efficacy along with Eli Lilly’s mAb LY-CoV555 they are planning to also test a cocktail of the two mAb therapies in combination to check for greater efficacy.

Table 1 – Current COVID-19 Monoclonal Antibody Therapy Trials