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Bovhyaluronidaze azoximer significantly reduces exercise intolerance in patients with long-term pulmonary sequelae of COVID-19

2024-12-12
(Press-News.org) Petrovax announced today the positive results from “Long-CoV-III-21,” a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of bovhyaluronidase azoximer in adult patients with pulmonary sequelae of COVID-19. Bovhyaluronidase azoximer, marketed under the brand name Longidaza, is a polymer-conjugated hyaluronidase with an extended half-life. The study drug and placebo were administered for 71 days, with an observation period extending to Day 180.

Longidaza demonstrated a statistically significant 62% reduction in the proportion of patients with exertional desaturation (OR = 0.35, p = 0.0051) and a 27% reduction in the proportion of patients exhibiting exertional dyspnea (OR = 0.62, p = 0.043) by Day 71 compared to placebo. Marked improvements were also observed in resting dyspnea and distance walked during the six-minute walk test. The drug's effects on exercise tolerance indicators were sustained for more than 100 days after the last dose.

Longidaza did not affect pulmonary function in the overall population. However, subgroup analysis revealed that the drug was associated with a significantly greater change from baseline in predicted Forced Vital Capacity (FVC) in patients with cardiovascular comorbidities (difference = 3.31%, p = 0.042) and in those infected with earlier variants of SARS-CoV-2 (difference = 4.17%, p = 0.021) compared to placebo.

“Long-CoV-III-21 is among the first randomized, double-blind trials to show a significant effect of a novel therapy in patients with post-COVID pulmonary sequelae. The sustained effects of Longidaza offer hope for patients struggling with dyspnea, fatigue, and reduced physical capacity to improve their quality of life,” said Sergey Avdeev, MD, Chair of the Pulmonology Department at Sechenov University and principal investigator of the trial. “Although the drug did not show a significant effect on pulmonary function recovery in the entire study population, results in subgroups strongly suggest that research into hyaluronidase-based medications should continue—not only for post-COVID pulmonary sequelae but also for other fibrotic conditions.”

Study findings were presented at the Asian Pacific Society of Respirology congress in Hong Kong.

In parallel with long COVID research, Petrovax has been developing an inhaled form of Longidaza for the treatment of interstitial lung diseases. The safety of this new delivery route was demonstrated in a recent Phase 1 study. A Phase 2 trial of inhaled Longidaza in patients with idiopathic pulmonary fibrosis is planned for 2025.

About Long-CoV-III-21

Long-CoV-III-21 is a prospective, randomized, double-blind, placebo-controlled clinical trial designed to test the efficacy and safety of Longidaza (3000U) intramuscular injections in patients with pulmonary sequelae of COVID-19 (NCT06383819). Three hundred ninety-two patients were randomized 1:1 to receive either Longidaza or placebo every 5 days for 71 days. The follow-up period lasted up to Day 180. The study enrolled patients with a history of COVID-19 infection 1 to 12 months prior to screening, restrictive lung disease, fibrotic-like radiological abnormalities in the lungs, and decreased SpO2 at rest or after exertion. The study was conducted at 37 clinical sites.

The primary endpoint was the change from baseline in predicted Forced Vital Capacity.

The main secondary endpoints included the proportions of patients with exertional desaturation and dyspnea after the six-minute walk test, the distance walked in the six-minute walk test, and dyspnea at rest.

About Long COVID and Pulmonary Sequelae of COVID-19

Long COVID affects a significant portion of COVID-19 patients, with studies estimating its prevalence at approximately 10-20% of those infected. Long COVID impacts several organ systems, leading to a variety of symptoms, including persistent fatigue, breathlessness, and exercise intolerance, which can last for months or even years beyond the initial infection. A subset of patients with long COVID develop pulmonary sequelae, characterized by fibrotic-like changes in the lungs (assessed by CT), respiratory symptoms, and restrictive-type pulmonary function impairment. Currently, these patients are treated with antifibrotics, steroids, immunosuppressant medications and n-acetyl cysteine. However, all of these approaches lack high-quality evidence specific to post-COVID pulmonary sequelae.

“It may seem that we are past COVID-19, but a recent CDC survey shows that 7% of U.S. adults have had long COVID—about 17 million people. Developing effective therapies to help patients recover is crucial,” says Sergey Avdeev.

About Hyaluronic Acid and Longidaza

Recent research shows that hyaluronic acid is not only a structural component of the extracellular matrix but also a key regulator of fibrotic tissue remodeling and chronic inflammation — key mechanisms of post-COVID pulmonary sequelae. Longidaza (bovhyaluroniodaze azoximer) is a polymer-conjugated hyaluronidase with over 20 years of clinical use, a well-established safety profile, and a prolonged half-life. It has been used clinically as an anti-inflammatory and anti-adhesion therapy. Preclinical studies have demonstrated Longidaza’s potential to reduce fibrosis, while a pilot study involving 160 post-COVID-19 patients showed statistically significant improvements in pulmonary function, respiratory symptoms, and exercise tolerance.

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[Press-News.org] Bovhyaluronidaze azoximer significantly reduces exercise intolerance in patients with long-term pulmonary sequelae of COVID-19