HONG KONG – Covig-19, an anti-SARS-CoV-2 hyperimmune immunoglobulin (h-Ig) therapy that Takeda Pharmaceutical Co. Ltd. developed alongside the Covig-19 Plasma Alliance, has failed to meet its endpoints in a global phase III trial. The multicenter Inpatient Treatment with Anti-Coronavirus Immunoglobulin trial was sponsored and funded by the National Institute of Allergy and Infectious Diseases. It aimed to demonstrate the drug’s safety, tolerability and efficacy in hospitalized adults at the onset of COVID-19 progression, the companies said.

Julie Kim, president of plasma-derived therapies business unit, Takeda

“The trial was unable to show meaningful improvement in the clinical status of hospitalized, adult COVID-19 patients through treatment with Covig-19 when given with standard of care including remdesivir,” Julie Kim, president at Takeda’s plasma-derived therapies business unit, told BioWorld. Kim, who co-leads the Covig-19 Plasma Alliance, added that NIAID will publish the findings from the trial shortly.

The trial evaluated Covig-19’s efficacy and safety in addition to the standard of care. As Gilead Sciences Inc.’s antiviral agent Veklury (remdesivir) is the standard of care in most geographies, it was included in both the treatment and placebo arms of the study.

“The results conclude the alliance’s work and individual companies may choose to continue to evaluate the efficacy of h-Ig independently in other settings. Takeda is not yet ready to confirm plans but will make a decision based on patient need and in consideration of the rapidly evolving treatment landscape,” said Kim.

Despite the disappointment, no serious side effects were observed during the trial and the alliance’s work was not in vain.

Bill Mezzanotte, chief medical officer, executive vice president and R&D head, CSL Behring

“Science is as much about learning what does not work as it is about learning what does work. These findings will help build the library of understanding about the efficacy of antibody treatments against COVID-19, and clinical trial approaches to best explore the safety and efficacy of these varied therapies,” Bill Mezzanotte, chief medical officer at CSL Behring, told BioWorld. He also serves as executive vice president and R&D head at CSL and is a Covig-19 Plasma Alliance co-leader.

Osaka, Japan-based Takeda and CSL co-founded the alliance in April 2020, with the aim of developing a plasma-derived therapy for patients at risk for serious complications from COVID-19. Other members include Germany’s Biotest AG, France’s LFB SA, Switzerland’s Octapharma AG, Yongin, South Korea-based GC Pharma, Biopharma Plasma, National Bioproducts Institute and Sanquin, with the Bill & Melinda Gates Foundation providing advisory support.

What differentiates Covig-19 is that it is a polyclonal antibody while other COVID-19 therapies currently under development include monoclonal antibodies. “COVID convalescent plasma already received emergency authorization for direct transfusion since the early days of the pandemic. Covig-19 is distinct from this approach as it is a medicine that is made from plasma,” said Takeda’s Kim.

“The additional processing of the plasma-derived h-Ig therapy allows it to be standardized so it has a consistent level of virus-specific antibodies in each unit, and it can be administered in any blood group type unlike convalescent plasma. H-Ig also has a longer shelf life, which could make it easier to distribute and store,” she added.

Other approaches underway

Despite the setback for Covig-19, a multitude of additional approaches to COVID-19 treatment remain under development, such as Kintor Pharmaceutical Ltd.’s androgen receptor antagonist proxalutamide, which recently appeared to be yielding positive results in a preliminary analysis of phase III data from 590 hospitalized COVID-19 patients in Brazil. The analysis found the drug reduced mortality risk by 92% and shortened median hospital length stay by nine days compared to standard of care.

Celltrion Inc.’s anti-COVID-19 monoclonal antibody, Regkirona (regdanvimab), is also making headway, having won conditional marketing authorization from the Ministry of Food and Drug Safety in February 2021.

And Takeda itself is developing other weapons to fight COVID-19. It expects approval in Japan for two COVID-19 vaccines, TAK-919 and TAK-019, for which the company is collaborating Moderna Inc. and Novavax Inc. respectively.

Takeda is also taking on additional infectious disease challenges with programs such as its dengue vaccine candidate, TAK-003, for which the EMA recently accepted regulatory filings. The vaccine is being investigated for the prevention of dengue due to any dengue virus serotype in individuals ages four to 60. Takeda plans to make additional regulatory filings in Argentina, Brazil, Colombia, Indonesia, Malaysia, Mexico, Singapore, Sri Lanka and Thailand throughout 2021.

Takeda also recently bagged global rights to soticlestat, a first-in-class inhibitor of cholesterol 24-hydroxylase for the treatment of developmental and epileptic encephalopathies, from Ovid Therapeutics Inc. The pair are planning to start phase III trials testing the drug against Dravet and Lennox-Gastaut syndromes.