Biosimilar Developers and the Battle Against COVID-19

As the global pandemic cases topped 25 million by late summer 2020, many biosimilar manufacturers had joined the fight to find treatments for coronavirus disease 2019 (COVID-19). In some clinical trials, biosimilars are under evaluation, and in others, originator biologics are the focus, potentially creating opportunity for biosimilars.

Other trials feature novel antibody treatments designed by biosimilar developers. Overall, biopharmaceuticals have shown great promise for helping manage COVID-19—related health issues.

Biosimilars for COVID-19

Two biosimilars are directly involved in trials. One of them is Celltrion Healthcare’s infliximab biosimilar, Remsima, which is under evaluation in the phase 2 CATALYST trial. Investigators believe the drug used for treating inflammatory diseases has the potential to control cytokine release syndrome (CRS)—a sometimes dangerous immune response—associated with COVID-19.

“We hope that by using a treatment that is already used to treat inflammation in other autoimmune conditions we may be able to manage inflammation associated with COVID-19 early,” said one of the investigators, Sir Marc Feldmann, professor of immunology, University of Oxford. “If, when people are initially admitted to hospital, we are able to keep symptoms within manageable levels, this may reduce the number of patients who need to be admitted to intensive care.”

An additional biosimilar evaluated for effectiveness in patients with COVID-19 was CinnaGen’s biosimilar interferon (INF) beta-1a (ReciGen), an anti-inflammatory used to treat patients with multiple sclerosis. ReciGen was part of the first published study to evaluate the therapeutic efficacy of INF molecules in patients with COVID-19.

Investigators couldn’t study the effects of ReciGen as monotherapy because Iranian national guidelines mandate the use of hydroxychloroquine and lopinavir/ritonavir for patients hospitalized with COVID-19; however, the study revealed that ReciGen in combination with these agents helped resolve COVID-19—related fever in all enrolled patients.

Originators With Biosimilar Competition

Some original drug products that face biosimilar competition are undergoing trials to determine potential value in treating COVID-19, potentially allowing for lower-cost alternatives to be used as treatments down the road.

Although, Roche does not develop biosimilars, it is the owner of reference bevacizumab (Avastin), which has biosimilar competition in the United States and Europe. The oncology drug was employed in COVID-19—related phase 2/3 trials starting in April. Bevacizumab has shown promise for treatment of pulmonary edema—related acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Pulmonary edema is a condition caused by excess fluid in the lungs, and bevacizumab is an anti-VEGF drug thought to address ALI and ARDS by suppressing pulmonary edema.

Roche was also testing the rheumatoid arthritis originator product tocilizumab (Actemra), which has multiple biosimilar competitors in development. The tocilizumab reference product was approved by the FDA in August 2017. According to results of an observational study at Cedars-Sinai in Los Angeles, patients with COVID-19 who received tocilizumab had reduced inflammation, needed less oxygen and blood pressure support, and had a lower risk of death.

Alexion initiated COVID-19—related trials for the immunosuppressants eculizumab (Soliris) product and ravulizumab (Ultomiris), a Soliris follow-on product. Soliris’ phase 3 trials began recruitment in July 2020 and Ultomiris’ began in May 2020. Eculizumab is undergoing trials in patients with moderate, severe pneumonia or critical pneumonia associated with COVID-19. Ravulizumab is undergoing evaluation as a treatment for COVID-19—related severe pneumonia, acute lung injury, and acute respiratory distress syndrome.

Biologic Originators for COVID-19

Some biosimilar developers have entered their nonbiosimilar products into the ring to see how they fare against COVID-19.

One example is Biocon Biologics, whose itolizumab (Alzumab) product, used to treat psoriasis and psoriatic arthritis, received emergency use authorization in India for the treatment of CRS in patients with severe respiratory distress syndrome related to COVID-19. More clinical evaluation is anticipated.

Novartis’ canakinumab (Ilaris), an INT-1 beta blocker used in patients with active systemic juvenile idiopathic arthritis, is undergoing testing for treatment of patients with COVID-19—related pneumonia and CRS. Novartis owns Sandoz, which has multiple biosimilars, including the first FDA-approved biosimilar, Zarxio (2015), a filgrastim product.

Sanofi submitted a rheumatoid arthritis drug, sarilumab (Kevzara), to the clinical trials process; however, a US-based trial did not meet its primary and secondary end points and the trial was stopped. It was theorized that interleukin-6 inhibition would help to reduce fever and improve oxygenation in patients with COVID-19. A separate trial outside the United States using a different dosing regimen remained underway and results were anticipated in the third quarter of 2020.

Pfizer began testing its tofacitinib (Xeljanz) biologic as a treatment for controlling inflammation in patients with COVID-19. The drug is indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. The drug is being evaluated in patients with COVID-19—related pneumonia who require supplemental oxygen but not mechanical ventilation.

AstraZeneca, which in late summer 2020 was awaiting a European Commission marketing approval decision for its bevacizumab biosimilar (Equidacent), was evaluating its acalabrutinib (Calquence) oncology product in patients with COVID-19—related acute respiratory distress syndrome. Initial results were promising with the Bruton tyrosine kinase inhibitor: decreased inflammation and improved outcomes.

Investigational Antibodies

In August, Celltrion Healthcare received approval from the Korean Ministry of Food and Drug Safety for a phase 1 clinical trial of CT-P59, a potential COVID-19 antiviral treatment made from antibodies from patients with COVID-19. Celltrion initiated enrollment of patients with mild COVID-19 symptoms. In July, the company initiated a separate phase 1 trial of CT-P59 in the United Kingdom.