ファイザーの新たな抗ウイルス剤PAXLOVID™は、COVID-19に対し、臨床試験において良好な成績を示した。

Pfizer Confirms COVID-19 Pill's Results, Potency Versus Omicron

あくまでも私見ではあるが、先日紹介したMerckのMolnupiravirより、PfizerのPAXLOVID™の方が、臨床的有用性は高い様に感じた。ただ、有効性の評価の方法 (臨床試験の設計) が異なるので、安易に比較することはよろしくないのですが。

BY MATTHEW PERRONE / TIME / DECEMBER 14, 2021

わたしのnoteにおいては、最新の科学・経済・社会等の問題に関して、英語の記事を引用し、その英文が読み易いように加工し、「英語の勉強ツール」と「最新情報収集ツール」としてご利用頂くことをmain missionとさせて頂きます。勿論、私論を書かせて頂くこともしばしです。

WASHINGTON — Pfizer said today that its experimental pill to treat COVID-19 appears effective against the omicron variant.

The company also said full results of its 2,250-person study confirmed the pill’s promising early results against the virus: The drug reduced combined hospitalizations and deaths by about 89% among high-risk adults when taken shortly after initial COVID-19 symptoms.

Separate laboratory testing shows the drug retains its potency against the omicron variant, the company announced, as many experts had predicted. Pfizer tested the antiviral drug against a man-made version of a key protein that omicron uses to reproduce itself.

The updates come as COVID-19 cases, deaths and hospitalization are all rising again and the U.S. hovers around 800,000 pandemic deaths. The latest surge, driven by the delta variant, is accelerating due to colder weather and more indoor gatherings, even as health officials brace for (～に備える、～に構える) the impact of the emerging omicron mutant.

The Food and Drug Administration is expected to soon rule on whether to authorize Pfizer’s pill and a competing pill from Merck, which was submitted to regulators several weeks earlier. If granted, the pills would be the first COVID-19 treatments that Americans could pick up at a pharmacy and take at home.

Pfizer’s data could help reassure regulators of its drug’s benefit after Merck disclosed smaller-than-expected benefits for its drug in final testing. Late last month, Merck said that its pill reduced hospitalizations and deaths by 30% in high-risk adults.

Both companies initially studied their drugs in [unvaccinated adults who face the gravest risks from COVID-19, due to older age or health problems, such as asthma or obesity].

Pfizer is also studying its pill in lower-risk adults—including a subset who are vaccinated—but reported mixed data for ＜that group＞ on Tuesday.

In interim results (臨床試験実施中の中間解析成績), Pfizer said its drug failed to meet its main study goal: sustained relief from COVID-19 for four days during or after treatment, as reported by patients. But the drug did achieve a second goal by reducing hospitalizations by about 70% among ＜that group＞, which included healthy unvaccinated adults and vaccinated adults with one or more health issues. Less than 1% of patients who got the drug were hospitalized, compared with 2.4% of patients who got a dummy pill.

An independent board of medical experts reviewed the data and recommended Pfizer continue the study to get the full results before proceeding further with regulators.

Across both of Pfizer’s studies, adults taking the company’s drug had a 10-fold decrease in virus levels compared with those on placebo.

The prospect of new pills to fight COVID-19 can’t come soon enough for communities in the Northeast and Midwest, where many hospitals are once again being overloaded by incoming virus cases.

Both the Merck and Pfizer pills are expected to perform well against omicron because they don’t target the coronavirus’ spike protein, which contains most of the new variant’s mutations.

Centers for Disease Control and Prevention Director Rochelle Walensky, appearing on NBC’s “Today” on Tuesday, said the best way for people to protect themselves against COVID-19 is to get vaccinated and get a booster shot. She said the Pfizer pill, if authorized by the FDA, “will be another great tool, but we need to diagnose people early.”

The U.S. government has agreed to purchase enough of Pfizer’s drug to treat 10 million people and enough of Merck’s to treat 3 million, pending FDA authorization.

Pfizer Announces Additional Phase 2/3 Study Results Confirming Robust (堅固な、頑強な/roubʌ́st) Efficacy of Novel COVID-19 Oral Antiviral Treatment Candidate in Reducing Risk of Hospitalization or Death

Posted: December 2021 / Source: Pfizer Inc.

• Final data available from all high-risk patients enrolled in EPIC-HR study (n= 2,246) confirmed prior results of interim analysis showing PAXLOVID™ (nirmatrelvirとritonavirの合剤：Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of nirmatrelvir in order for it to remain active：主役はnirmatrelvir) reduced risk of hospitalization or death by 89% (within three days of symptom onset) and 88% (within five days of symptom onset) compared to placebo; no deaths compared to placebo in non-hospitalized, high-risk adults with COVID-19.

• The above data have been shared with the U.S. Food and Drug Administration (FDA) as part of an ongoing rolling submission (早期承認・実用化の為、データを順次FDAに提出し審査の迅速化を図る) for Emergency Use Authorization (EUA：緊急承認).

• Separately, interim analyses of an ongoing second study in standard-risk adults (EPIC-SR) showed a 70% reduction in hospitalization and no deaths in the treated population, compared to placebo, in the secondary endpoint; the novel primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days, as compared to placebo, was not met. The study continues.

• An approximate 10-fold decrease in viral load at Day 5, relative to placebo, was observed in both EPIC-HR and EPIC-SR, indicating robust activity against SARS-CoV-2 and representing the strongest viral load reduction reported to date for a COVID-19 oral antiviral agent.

• Recent in vitro data confirm that nirmatrelvir is a potent inhibitor of the Omicron 3CL protease, which, [combined with existing in vitro antiviral and protease inhibition data from other Variants of Concern (VoC) including Delta], indicates that PAXLOVID will retain robust antiviral activity against current VoCs as well as other coronaviruses.

Pfizerの臨床試験データの詳細 (最終結果)
NEW YORK--(BUSINESS WIRE) December 14, 2021 -- Pfizer Inc. (NYSE: PFE) today announced final results from an analysis of all 2,246 adults enrolled in its Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) trial of its novel COVID-19 oral antiviral candidate PAXLOVID™ (nirmatrelvir and ritonavir). These results were consistent with the interim analysis announced in November 2021, showing PAXLOVID significantly reduced the risk of hospitalization or death for any cause by 89% compared to placebo in non-hospitalized, high-risk adult patients with COVID-19 treated within three days of symptom onset. In a secondary endpoint, PAXLOVID reduced the risk of hospitalization or death for any cause by 88% compared to placebo in patients treated within five days of symptom onset, an increase from the 85% observed in the interim analysis. The EPIC-HR data have been shared with the U.S. Food and Drug Administration (FDA) as part of an ongoing rolling submission for Emergency Use Authorization.

“This news provides further corroboration (実証するもの、裏付ける証拠/kərɑ̀bəréiʃən) that our oral antiviral candidate, if authorized or approved, could have a meaningful impact on the lives of many, as the data further support the efficacy of PAXLOVID in reducing hospitalization and death and show a substantial decrease in viral load. This underscores (強調する、明確に示す/ʌ̀ndərskɔ́r) the treatment candidate’s potential to save the lives of patients around the world,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “Emerging variants of concern, like Omicron, have exacerbated the need for accessible treatment options for those who contract the virus, and we are confident that, if authorized or approved, this potential treatment could be a critical tool to help quell the pandemic.”

EPIC-HR Final Results

In the final analysis of the primary endpoint from all patients enrolled in EPIC-HR, an 89% reduction in COVID-19-related hospitalization or death from any cause compared to placebo in ＜patients treated within three days of symptom onset＞ was observed, consistent with the interim analysis. In addition, a consistent safety profile was observed. 0.7% of patients who received PAXLOVID were hospitalized through Day 28 following randomization (5/697 hospitalized with no deaths), compared to 6.5% of patients who received placebo and were hospitalized or died (44/682 hospitalized with 9 subsequent deaths). The statistical significance (統計学的有意差) of these results was high (p<0.0001：有意差あり). In a secondary endpoint, PAXLOVID reduced the risk of hospitalization or death for any cause by 88% compared to placebo in ＜patients treated within five days of symptom onset＞; 0.8% of patients who received PAXLOVID were hospitalized or died through Day 28 following randomization (8/1039 hospitalized with no deaths), compared to 6.3% of patients who received placebo (66/1046 hospitalized with 12 subsequent deaths), with high statistical significance (p<0.0001). Relative risk reduction was 94% in ＜patients 65 years of age or older, one of the populations at highest risk for hospitalization or death＞; 1.1% of patients who received PAXLOVID were hospitalized through Day 28 (1/94 hospitalized with no deaths), compared to 16.3% of patients who received placebo (16/98 hospitalized with 6 deaths), with high statistical significance (p<0.0001). In the overall study population through Day 28, no deaths were reported in patients who received PAXLOVID as compared to 12 (1.2%) deaths in patients who received placebo.

In the EPIC-HR trial, in a secondary endpoint, SARS-CoV-2 viral load at baseline and Day 5 have been evaluated for 499 patients. After accounting for baseline viral load, geographic region, and serology status, PAXLOVID reduced viral load by approximately 10-fold, or 0.93 log10 copies/mL, relative to placebo, indicating robust activity against SARS-CoV-2 and representing the strongest viral load reduction reported to date for an oral COVID-19 agent.

Treatment-emergent adverse events were comparable between PAXLOVID (23%) and placebo (24%), most of which were mild in intensity. Fewer serious adverse events (1.6% vs. 6.6%) and discontinuation of study drug due to adverse events (2.1% vs. 4.2%) were observed in patients dosed with PAXLOVID, compared to placebo, respectively.

All other secondary endpoints for this study were not yet available for this review. Full study data are expected to be released later this month and submitted to a peer-reviewed publication.

EPIC-SR Interim Results

Interim analyses of the EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) Phase 2/3 study, which included unvaccinated adults who were at standard risk (i.e., low risk of hospitalization or death) as well as vaccinated adults who had one or more risk factors for progressing to severe illness, showed that the novel primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days, as compared to placebo, was not met.

The key secondary endpoint showed a 70% reduction in hospitalization and no deaths in the treated population for any cause compared to placebo. Additionally, there was approximately a 10-fold, or 1 log10 copies/mL, decrease in viral load compared to placebo, consistent with results from the Phase 2/3 EPIC-HR study.

The data were reviewed by an independent Data Monitoring Committee (DMC) and, based on the totality of the data available, the DMC recommended that the trial continue.

At the EPIC-SR interim analysis, which included 45% of the trial’s planned enrollment, 0.6% of those who received PAXLOVID were hospitalized following randomization (2/333 hospitalized with no deaths), compared to 2.4% of patients who received placebo and were hospitalized or died (8/329 hospitalized with no deaths). A follow-on analysis at 80% of enrolled patients was consistent with these findings. In this analysis, 0.7% of those who received PAXLOVID were hospitalized following randomization (3/428 hospitalized with no deaths), compared to 2.4% of patients who received placebo and were hospitalized or died (10/426 hospitalized with no deaths); p=0.051 (一般的に、p＜0.05であれば統計学的に有意差ありと考える。よって、p=0.051は0.05より大きいので、有意差無しと解釈する).

Treatment-emergent adverse events were comparable between PAXLOVID (22%) and placebo (21%), most of which were mild in intensity. Rates of serious adverse events (1.4% vs. 1.9%) and discontinuation of study drug due to adverse events (2.1% vs. 1.2%) were also comparable between PAXLOVID and placebo.

All other secondary endpoints for this study were not yet available for this review. The study is now fully enrolled, and further data will be released upon analysis of the full study data expected later this month.