Repurposed drugs became the front-line defense against COVID-19 within a few months of the pandemic’s emergence. Now bucillamine, currently in Phase III trials in the U.S., may be poised to join them.
Repurposed drugs became the front-line defense against COVID-19 within a few months of the pandemic’s emergence. Now bucillamine, currently in Phase III trials in the U.S., may be poised to join them.
Used in Japan and South Korea as an arthritis treatment for the past 30 years, Canadian firm Revive Therapeutics is putting it through its paces as a possible oral, at-home therapy for mild to moderate COVID-19.
Although more than 2.24 billion doses of COVID-19 vaccines have been administered globally, according to Johns Hopkins University COVID-19 Tracker, “there is still a need for COVID-19 therapies, particularly small molecule drugs,” Revive Therapeutics’ CEO Michael Frank told BioSpace. “The COVID-19 therapies on the market now tend to be administered intravenously. Additionally, a lot of people don’t want to take vaccines, and the logistics of rolling treatments for COVID-19 around the world are still challenging. Health experts also are eyeing the possibility of another round of pandemic as the SARS-CoV-2 virus mutates.
“Right now, there are only a handful of companies with an oral drug for COVID-19 in Phase III trials,” he said.
Merck, for example, just signed a $1.2 billion contract with the U.S. Army Contracting Command to supply 1.7 million courses of treatment, assuming molnupiravir receives emergency use authorization. Bucillimine, he reasoned, could fill a treatment niche as well.
“We repurposed bucillamine for gout in about 2015,” Frank said. “We conducted a Phase IIa study and achieved favorable results compared to colchicine…but didn’t pursue it.”
Frank went on to explain the reasoning behind that decision.
“There wasn’t a lot of interest in funding another gout treatment then,” he said. “It was a matter of interest and at the time, CBD was picking up popularity in the market.” Therefore, the company shifted its focus to CBD drugs. “Bucillamine went into our war chest.”
When Frank became CEO of Revive Therapeutics in December 2019, he reviewed the portfolio and continued the company’s CBD focus. He began working with the University of Wisconsin with delivery systems and the University of North Carolina regarding the biosynthesis of psilocybin.
“Then COVID-19 got rambunctious,” he said, so he revisited bucillamine. It had a 30-year safety profile in Asia for rheumatoid arthritis, showed good preclinical data, and had antirheumatic, anti-inflammatory, and anti-oxidant properties. The mechanism of action was favorable, too, with a dual-field method of metabolizing in the liver.
“Last summer, we took the drug to the FDA for infectious disease and ultimately focused on COVID-19,” Frank said.
Last July, it was approved to begin a Phase III study for mild-to-moderate cases of COVID-19, bypassing Phase I and II trials.
Preliminary results are expected by Q3 from the double-blind, placebo-controlled study.
The trial compares 100mg and 200mg doses of bucillamine, administered three times daily, and placebo, according to ClinicalTrials.gov. The primary endpoint is reduced hospitalization and/or death.
We are working to expand the study to 50 sites and up to 1,000 patients. We should have up to 400 patients by the end of Q2 and the study will finish by Q3.
Because the study is double-blind, Frank has no insight at this point regarding efficacy.
Ultimately, it appears possible to apply this long-standing arthritic drug to treat inflammation in the lungs, liver, and heart, and as a therapy for COVID-19 long-haulers.
“It also may be effective for cystic fibrosis patients,” he said. “It’s a very versatile drug.”
Revive Therapeutics is a small company, and competing therapeutics are being developed by companies with more resources. Frank is hoping the easy administration of this oral medication may give it an edge against possibly better-funded competitors that require IV administration.
In his less than two years as CEO, Frank is succeeding at improving the company’s coffers and prospects. He has taken Revive Therapeutics from a $1.4 million CAD company to one worth more than $100 million CAD, and recently raised $25 million CAD.
Revive Therapeutics also just signed a partnership deal with Supriya Lifescience Ltd., a specialty pharmaceutical company based in India, to manufacture the active pharmaceutical ingredients, conduct clinical registration, and commercialize bucillamine to treat COVID-19 in India under an emergency use authorization (EUA).
If an EUA is granted, this agreement helps fills urgent needs in India for COVID-19 medications and helps Revive expand its global manufacturing and commercialization plans by accessing Supriya’s 78-country customer base.
One month earlier, Revive Therapeutics signed a research agreement with the University of California – San Francisco to test the efficacy of bucillamine against severe COVID-19 cases and design protocols for additional human trials.
The research will be conducted by the laboratory of pulmonologist John Fahy, M.D., director of UCSF’s severe asthma clinic. He recently conducted research on thiol-based drugs (like bucillamine), finding that they decrease the binding of the SARS-CoV-2 spike protein to its receptor, thus helping prevent infections.
