HONG KONG – A Japanese phase III study of Chugai Pharmaceutical Co. Ltd.’s interleukin-6 inhibitor, Actemra (tocilizumab), in patients hospitalized with severe COVID-19 pneumonia has read out, expanding what’s known about the drug’s use in the pandemic, which had been inconclusive until recently, though is now known to reduce mortality in the vulnerable population.

The primary endpoint of the trial, run between May and October 2020, was clinical status assessed using a seven-category ordinal scale 28 days after treatment. The scale ranged from 1, indicating discharged or ready to be discharged from hospital, to 7, indicating death, and was defined based on the necessity of extracorporeal membrane oxygenation, mechanical ventilation and supplemental oxygen. Key secondary endpoints included time to clinical status improvement and time to discharge or ready to discharge.

Results of the single-arm trial, J-Covacta, showed that 35, or 72.9%, of 48 patients treated with Actemra plus standard of care were discharged or became ready to be discharged from the hospital 28 days after treatment, while five, or 10.4%, died. The results also showed that 39 patients, or 81.3%, improved in at least one category on the scale at day 28 compared with the previous treatment, while six patients, or 12.5%, worsened in at least one category.

The drug’s safety was comparable with the known safety profile, with no new safety signals identified. The results will be presented at a future medical meeting after further analysis.

“As J-Covacta is a single-arm study, we need to interpret the results in conjunction with global studies,” Tomoko Shimizu, Chugai’s head of media relations, told BioWorld.

Indeed, the study is part of much broader effort by Chugai’s parent company, Roche Holding AG and global health authorities it evaluate the use of IL-6 inhibitors in treating COVID-19. The phase III Remdacta study, in combination with Veklury (remdesivir, Gilead Sciences Inc.) and standard of care in hospitalized patients with severe COVID-19 associated pneumonia, is currently ongoing. Roche also released results from both the phase III Covacta study in hospitalized patients with severe COVID-19-associated pneumonia in July 2020, and those from the phase III Empacta study in hospitalized patients with COVID-19-associated pneumonia two months later.

In terms of other potential indications, phase I studies are currently underway for a combination therapy with humanized anti-PD-L1 monoclonal antibody Tecentriq (atezolizumab, Roche Holding AG) to treat pancreatic adenocarcinoma. The company plans to file for additional indications based on the J-Covacta results alongside results from other studies.

Actemra has been available on the global market for more than 10 years for the treatment of rheumatoid arthritis and other autoimmune diseases but is currently not approved by any health authorities for the treatment of COVID-19-associated pneumonia yet, Shimizu said.

Change at the top

The company has also seen a change at the managerial level, with current representative director, president and chief operating officer Osamu Okuda appointed as the CEO earlier in the month. Okuda will begin his term on March 23, after which current CEO Tatsuro Kosaka will continue to chair the board in his capacity as representative director and chairman.

Founded in March 1925, Chugai is also keeping busy with other candidates in its pipeline. It has plans to start clinical development for a midsized molecule drug in 2021, said Shimizu.

Japan’s Ministry of Health, Labour and Welfare (MHLW) approved an additional indication in September 2020 for a combination of Tecentriq and humanized anti-vascular endothelial growth factor monoclonal antibody Avastin (bevacizumab, Roche Holding AG). The pair is now approved for patients with unresectable hepatocellular carcinoma

Chugai also launched a subcutaneous injection form of Enspryng (satralizumab) in Japan to prevent relapses of neuromyelitis optica spectrum disorder, including neuromyelitis optica, in August 2020.

The company is also developing a digital solution for measuring pain levels in endometriosis patients with Boston-based Biofourmis Inc. The device will use Biovitals, Biofourmis' artificial intelligence health analytics platform, to predict clinical exacerbation in advance of a critical event to help endometriosis patients measure their pain levels as objectively as possible.

Meanwhile, Japan continues its fight against COVID-19. MLHW recently approved the the Pfizer-Biontech COVID-19 vaccine, co-developed by Pfizer Inc. and Biontech SE. An application was submitted on Dec. 18, 2020, and Pfizer Japan Inc. signed a final agreement a month later to provide around 144 million doses of the jab in 2021. Inoculation is set to begin on Feb. 17 in preparation for the Tokyo summer Olympic games, due to begin on July 23.