On October 1, the United States Merck announced the interim clinical data of the Phase III of the new crown drug "Molnupiravir", which showed that the mortality rate was reduced by 50%. The news that "the first anti-viral oral drug for new coronavirus is expected to be approved" spread wildly. The Health Times found that from September to the end of the year, in addition to "Molnupiravir", there are three major oral drug for new coronavirus in the world that will disclose phase 3 clinical data one by one.
Generally, after the 3rd mid-term data statistics are released, the research and development party can apply for EUA (emergency use authorization). The approval of EUA means that the drug can be legally launched on the market. As for formal approval, pharmaceutical companies generally apply in the later stage by submitting more detailed efficacy and safety data.
Kaituo Pharmaceutical Pukeluamide: the first new crown oral drug
Pukeluamide to conduct phase 3 clinical trials in China is an AR (androgen receptor androgenreceptor) antagonist developed by Kaituo Pharmaceutical. Purkluamide was originally a drug for treating prostate cancer . Kaituo Pharmaceutical discovered through experiments in February 2020 that Purkluamide can degrade ACE2 and TMPRSS2 proteins. At the same time, compared with other AR drugs, prkulamide can further reduce AR gene expression, so it is more likely to treat new crown .
For patients with severe COVID-19 patients, there may be another pathway for prikluamide, which can inhibit immune storms and inflammatory storms, but it has not been confirmed yet. In addition, this drug may also have certain undiscovered therapeutic mechanisms for the new coronavirus.
It is worth mentioning that Kaituo announced at noon on September 1: Kaituo Pharmaceutical has obtained the approval of National Drug Administration and conducted two phase 3 clinical trials in China, which are intended to be used to treat novel coronavirus pneumonia for mild and moderate and hospitalized severe patients.
Roche AT-527: Used as a prophylactic treatment after exposure
AT-527 is also an RNA polymerase inhibitor. After AT-527 enters the human body, it can then produce the triphosphate metabolite AT-9010, which has a higher activity against the new coronavirus. The activity of anti-new coronavirus in vitro is 5-8 times higher than that of Molnupiravir. Since AT-527 can target two polymerases that are crucial for viral RNA replication and transcription, including RNA-dependent RNA polymerase (RdRP), it has a unique dual inhibitory mechanism for the new coronavirus.
The drug was developed by Atea, and Roche received the right to treat AT-527 outside the United States for upfront payments and subsequent milestone payments. The company believes that this drug can not only be used as an oral therapy for hospitalized COVID-19 patients, but may also become the first oral treatment option for non-hospitalized patients, but also has the potential to be a prophylactic treatment after exposure.
On June 30, 2021, Atea released preliminary data on hospitalized patients with phase II clinical double-blind treatment of AT-527: 62 patients, 550mgBID, administered for 5 days. On the second day of treatment, the viral load in the AT-527 group decreased by 0.7 log (80%) compared with placebo; on day 14, 47% of the patients in the AT-527 group turned negative, and 22% of the patients in the comfort unit turned negative.
Pfizer PF-07321332: It can work on all current new coronavirus variants
PF-07321332 is a 3CL protease inhibitor that plays an important role in the life cycle of various coronaviruses. Its potential advantage is that it can work on all current new coronavirus variants.
Pfizer 's PF-07321332 has broad-spectrum anti-coronavirus capability. Although the virus may still mutate in theory to escape its mechanism of action, the actual chance of occurrence is very small. Pfizer also believed that the drug was expected to obtain EUA in the fourth quarter of this year. In clinical trials, Pfizer used a combination therapy of PF-07321332+ ritonavir .
According to clinical registration data, Wall Street Journal and Jianzhi Institute predicts that except for the RNA polymerase inhibitor of Merck , the other three oral new coronavirus drugs are expected to disclose phase 3 clinical data in Q4 this year. If positive results are obtained, the fast-moving products are expected to obtain emergency use authorization (EUA) in Europe, the United States and South America before the end of 2021.(Liu Yingqi)
Reference:
① 2021-10-02 Daily Economic News "Merk's new crown oral treatment drugs may reduce hospitalization and mortality rates by half, Merck's stock price once soared by 12%"
② 2021-09-27 Financial World "Kaituo Pharmaceutical's Phase III clinical trial for hospitalized COVID-19 patients approved in Brazil"
③ 2021-09-27 Financial World "Pfizer launches the effect of new crown oral drugs to prevent infections II/III trials, competition in track has entered the sprint stage"
④ 2021-09-28 New York Time "New crown oral drugs are coming soon"
⑤ 2021-09-02 Wall Street News "The new crown oral medicine is about to come out? Pay attention to these 4 companies in the fourth quarter"
