Medical Information

Shionogi & Co. on Friday submitted an application for conditional early approval for Japan's first domestically developed COVID-19 pill, which the government hopes could be a “trump card” in preventing serious illness and bringing an end to the prolonged pandemic.

Prime Minister Fumio Kishida has signaled the central government will expedite the review process to pave the way for a swift approval if the drug's efficacy and safety are confirmed. Shionogi has said it hopes to begin shipments of the treatment as soon as the end of this month.

If formally approved, Shionogi’s experimental drug would become the third COVID-19 oral anti-viral pill for the treatment of mild symptoms to be given the OK in Japan, after Merck & Co.'s molnupiravir and Pfizer Inc.’s Paxlovid.

Paxlovid shipments began Feb. 14 after it received health ministry authorization earlier this month. But a steep rise in COVID-19 cases driven by the omicron variant brought about a surge in demand for oral drugs and antibody treatments for mildly and moderately ill patients, with some hospitals and pharmacies complaining of a lack of supplies.

Dr. Takeshi Urano, a professor of pathological chemistry at Shimane University’s Faculty of Medicine, says the oral drugs that can be used to treat mild symptoms could be a game-changer in the prolonged fight against the coronavirus.

“Shionogi’s drug seems promising, and it would add to the arsenal of excellent drug options and relieve the burden on doctors,” he said.

Experts say Shionogi’s drug may have high potential, as it and Pfizer’s pill target the same enzyme, known as 3CL protease, which plays an essential role in viral replication for various coronaviruses. Paxlovid has shown 89% efficacy in preventing hospitalizations and deaths in high-risk adults when it is taken within three days of the patient developing symptoms.

In comparison, Merck’s molnupiravir, originally developed to treat influenza, combats various viruses by disrupting ribonucleic acid (RNA) polymerase, an enzyme that the virus uses to replicate itself. The drug incorporates RNA-like building blocks into the genome of the coronavirus and causes a series of errors that make the virus’s replication harder. During clinical trials, it was shown to reduce the risk of hospitalization or death by 30%.

While ritonavir, one of the two pills that comprises Paxlovid along with nirmatrelvir, has been used for decades as an anti-HIV medication, Shionogi’s drug is a newly discovered therapeutic agent, according to Dr. Masahiro Kami, executive director of the Medical Governance Research Institute in Tokyo.

Compared with Shionogi’s pills, Pfizer’s Paxlovid is a delicate drug because doctors have to carefully review the patient’s existing medication to avoid harmful drug interactions, Kami said.

“The manual says to reduce Paxlovid’s dosage for people with poor kidney function, for example, but it's difficult to prescribe such a drug,” he said. “In that sense, Shionogi’s pill is easier to use.”

Shionogi’s drug, which was created through joint research with Hokkaido University, has been confirmed to exhibit high anti-viral activity against the omicron variant, as was the case with other variants.

The Osaka-based company said that it made the filing on Friday after its mid-stage clinical trial, which involved 428 COVID-19 patients, showed that the drug achieved a a significant and rapid anti-viral effect. The company said the trial was not able to show a significant difference in treating all the symptoms it was intended to when compared with a placebo, but added that it had confirmed a significant improvement in respiratory symptoms such as stuffy nose, sore throat, cough and shortness of breath. There were no new adverse events of concern.

Shionogi made the filing based on its analysis of the mid-stage trial without waiting for the completion of a final-phase large clinical trial that is now underway.

Kami says that Shionogi and Pfizer’s drugs have the same mechanism, and that may mean that one of them will outlast the other.

“We need to collect a lot of clinical data in this world, so it's all about data. It doesn't matter which one is really better,” he said. “In terms of the number of clinical trials, there’s a big difference. Pfizer is quick and has worked on clinical trials for people with bad livers and kidneys. Meanwhile, Shionogi hasn’t even finished the first large clinical trial yet. In that sense, Shionogi is at a little disadvantage.”

Reference

https://www.japantimes.co.jp/news/2022/02/25/national/science-health/shionogi-pill-approval-application/