Pfizer’s Novel COVID-19 Oral Antiviral Treatment Authorised for Supply and Use by the MHRA
- Medicines and Healthcare products Regulatory Agency (MHRA) grants GB conditional marketing authorisation for the supply and use of PAXLOVID®▼ (PF-07321332 tablets and ritonavir tablets) in adults who do not require supplemental oxygen and are at increased risk for progression to severe COVID-19
- PF-07321332/ritonavir is the first orally administered coronavirus-specific protease inhibitor
- Pfizer UK has an agreement with the UK Government to supply 2.75 million treatment courses during 20221
Walton Oaks, UK, 31st December 2021 – Pfizer UK announced today that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted a conditional marketing authorisation for Great Britain for the supply and use of PF-07321332/ritonavir for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progression to severe disease.*
PF-07321332/ritonavir is a novel protease inhibitor that includes PF-07321332, a drug designed to block the activity of the 3C-like (3CL) protease, also known as the main protease (Mpro) inhibitor, that was specifically designed in Pfizer’s laboratories to combat SARS-CoV-2. 3CL protease is a virally encoded protein that is essential to enable the virus to replicate; by inhibiting this viral protein, PF-07321332 reduces the ability of the virus to reproduce. PF-07321332 is co-administered with a low dose of ritonavir to help slow the metabolism, or breakdown, of PF-07321332 so that it remains active in the body for longer periods of time at higher concentrations to help combat the virus. Under this authorisation, PF-07321332/ritonavir can be prescribed as an at-home treatment, potentially helping patients avoid severe illness.
“This milestone is an important moment in our continued fight against COVID-19, offering the NHS another possible treatment option as cases continue to rise,” said Ben Osborn, Country Manager at Pfizer UK. “This at-home therapy, shown in clinical trials to reduce hospitalisations and save lives, has the potential to lessen the devastating impact of a virus that has now taken over 5 million lives globally.”
The MHRA based its decision on positive results from the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) interim analysis, which enrolled 1,219 non-hospitalised adults with confirmed COVID-19 who were at increased risk of progressing to severe illness.2 607 patients received PF-07321332/ritonavir and 612 patients received placebo.2
These interim data showed that, compared to placebo, adults treated with PF-07321332/ritonavir experienced a statistically significant reduction in risk of COVID-19-related hospitalisation or death from any cause when treatment was started within either three days (89% relative risk reduction;2 6.32% absolute risk reduction;3 p<0.0001)2 or five days (85% relative risk reduction;4 5.77% absolute risk reduction;3 p<0.0001)2 of symptom onset. There were no deaths in the active treatment groups.2 Adverse reactions in the PF-07321332/ritonavir group (≥ 1%) that occurred at a greater frequency than in the placebo group were diarrhoea (3.9% and 1.9%, respectively), vomiting (1.3% and 0.3%) and altered taste (4.8% and 0.1%).5
Pfizer recently announced that results from the final analysis of the primary endpoint from all patients enrolled in EPIC-HR were consistent with the interim analysis4 although these data were not included in the MHRA submission. Additionally, Phase 2/3 clinical trials are ongoing in adults at standard risk of progressing to severe illness, and in those who have been exposed to the virus through household contacts.4 Again, these data were not included in the MHRA submission and are not currently licensed.
In December 2021, Pfizer announced an agreement with the UK Government to supply an additional 2.5 million treatment courses of PF-07321332/ritonavir during 2022.1 This is in addition to the 250,000 treatment courses previously agreed in October 2021. With the oral antiviral treatment now authorised for supply and use, Pfizer will begin delivering the first treatment courses in Great Britain in early 2022.*
*A temporary Regulation 174 authorisation is in place to supply Northern Ireland.
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About PF-07321332/ritonavir tablets
PF-07321332/ritonavir is a SARS-CoV-2 protease inhibitor antiviral therapy. It was developed to be administered orally so that it can be taken at home as soon as possible after positive results of direct SARS-CoV-2 viral testing – potentially helping patients avoid severe illness. PF-07321332, which was developed in Pfizer’s laboratories, is designed to block the activity of the SARS-CoV-2-3CL protease, an enzyme that the coronavirus needs to replicate. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of PF-07321332 in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.
PF-07321332 is designed to inhibit viral replication at a stage known as proteolysis, which occurs before viral RNA replication. In preclinical studies, PF-07321332 did not demonstrate evidence of mutagenic DNA interactions.7
Current variants of concern have demonstrated mutations at the spike protein expressed on the surface of the SARS-CoV-2 virus. PF-07321332/ritonavir, however, works intracellularly on the protease of the SARS-CoV-2 virus by inhibiting viral replication. PF-07321332 has shown consistent in vitro antiviral activity against the previously identified variants of concerns (i.e., alpha, beta, delta, gamma, lambda, and mu).4 In addition, PF-07321332 potently inhibited the 3CL protease associated with Omicron in an in vitro biochemical assay.4 This indicates PF-07321332’s potential to maintain antiviral activity against Omicron. Additional in vitro antiviral studies with this variant are underway.4
PF-07321332/ritonavir is authorised to be administered at a dose of 300 mg (two 150 mg tablets) of PF-07321332 with one 100 mg tablet of ritonavir, given twice-daily for five days. One carton contains five blister packs of PF-07321332/ritonavir, as co-packaged PF-07321332 tablets with ritonavir tablets, providing all required doses for a full five-day treatment course.
For further information about PF-07321332/ritonavir, please refer to the attached Summary of Product Characteristics.
About the EPIC Development Programme
The EPIC (Evaluation of Protease Inhibition for COVID-19) Phase 2/3 development programme for PF-07321332/ritonavir consists of three clinical trials spanning a broad spectrum of patients, including adults who have been exposed to the virus through household contacts, as well as adults at both standard risk and high risk of progressing to severe illness.
In July 2021, Pfizer initiated the first of these trials, known as EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients), a randomised, double-blind study of non-hospitalised adult patients with COVID-19, who are at high risk of progressing to severe illness. At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. Food and Drug Administration (FDA), Pfizer ceased further enrolment into the study in early November 2021 due to the overwhelming efficacy demonstrated in results from an interim analysis.2 Findings from the EPIC-HR interim analysis have been submitted to a peer-reviewed journal for publication.
In August 2021, Pfizer began the Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients), to evaluate efficacy and safety in patients with a confirmed diagnosis of SARS-CoV-2 infection who are at standard risk (i.e., standard risk of hospitalisation or death). EPIC-SR includes a cohort of vaccinated adults who have an acute breakthrough symptomatic COVID-19 infection and who have risk factors for severe illness. Interim data from this study have been reported. In September, Pfizer initiated the Phase 2/3 EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) to evaluate efficacy and safety in adults exposed to SARS-CoV-2 by a household member. These trials are ongoing.
For more information on the EPIC Phase 2/3 clinical trials for PF-07321332/ritonavir, visit clinicaltrials.gov.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. In the UK, Pfizer has its business headquarters in Surrey and is a major supplier of medicines to the NHS. To learn more about our commitments, please visit us at www.pfizer.co.uk or follow us on Twitter (@Pfizer_UK), Facebook (@PfizerUK) and Instagram (@pfizeruk).
- DHSC press release. Available at: https://www.gov.uk/government/news/uk-secures-millions-more-antivirals-to-help-fight-omicron. [Last accessed: December 2021]
- Pfizer press release. Available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate. [Last accessed: December 2021]
- Pfizer data on file
- Pfizer press release. Available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-additional-phase-23-study-results. [Last accessed: December 2021]
- PAXLOVID®▼ Summary of Product Characteristics
- DHSC press release. Available at: https://www.gov.uk/government/news/uk-government-secures-groundbreaking-covid-19-antivirals. [Last accessed: December 2021]
- Owen DR, Allerton CMN et al. An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19. Available at: https://www-science-org.eu1.proxy.openathens.net/doi/10.1126/science.abl4784. [Last accessed: December 2021]