Pfizer Inc. (NYSE: PFE) announced today that it will further strengthen its commitment to United States manufacturing with a $120 million investment at its Kalamazoo, Michigan, facility, enabling U.S.-based production in support of its COVID-19 oral treatment, PAXLOVIDTM (nirmatrelvir [PF-07321332] tablets and ritonavir tablets). The investment will expand the production of active pharmaceutical ingredient (API) and registered starting materials (RSMs) used in the manufacture of nirmatrelvir, a novel main protease (Mpro) inhibitor originating in Pfizer's laboratories, which will create more than 250 additional high-skilled jobs at Pfizer's Kalamazoo site. This investment is another major step in Pfizer's effort to bring more key biopharmaceutical manufacturing to the U.S., increasing Pfizer's capability to produce and supply treatments and medicines for patients in the U.S. and around the world.
"Pfizer Global Supply has made the impossible possible, making billions of vaccine doses and now millions of treatment courses to help battle the deadly COVID-19 pandemic," said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. "By increasing production at our Michigan facility, we are both helping patients around the world and expanding important manufacturing innovation to the U.S. This investment builds upon our $5 billion of investments across our manufacturing and distribution portfolio since 2017 to support the ongoing growth of U.S. manufacturing leadership."
RSMs are the raw materials that are chemically converted into API, which is the active ingredient in a medicine. Producing PAXLOVID requires a significant amount of manufacturing capacity across all aspects of the production process. To date, Pfizer has shipped 12 million courses of PAXLOVID across 37 countries, including 5 million courses shipped to the U.S., and has manufactured almost 17 million treatment courses total. The significant investment being made in stateside API and RSM production for nirmatrelvir will allow Pfizer to increase supply capacity for PAXLOVID as needed to help meet global demand. With this new investment, Kalamazoo will be among the world's largest producers of API, with the capacity to produce 1,200 metric tons annually.
"Pfizer's $120 million expansion in Kalamazoo creating 250 good-paying jobs to support the manufacture of PAXLOVID will build on Michigan's economic momentum," said Governor Gretchen Whitmer. "Pfizer's Kalamazoo facility also made some of the first doses of the vaccine, and now this proud Michigan company will play an even more critical role in the fight against COVID-19. By creating opportunities for Michiganders, Pfizer is helping us grow our economy, create good-paying jobs, and help families."
Pfizer also plans to expand its Modular Aseptic Processing (MAP) sterile injectable pharmaceutical production facility in Kalamazoo with a phase two investment. The expansion adds to the initial investment of $450 million in phase one to build a 400,000-square-foot production facility and further establishes Kalamazoo as one of the most technically advanced sterile injectable pharmaceutical production facilities in the world.
"Pfizer's Kalamazoo facility has been at the forefront of pharmaceutical manufacturing for more than 135 years through the legacy company Upjohn," said Mike McDermott, Chief Global Supply Officer, Pfizer. "The Kalamazoo facility uses some of our most innovative manufacturing technology and has been essential in Pfizer's fight against COVID-19, producing nearly one billion doses of COVID-19 vaccine at the site to date. Through this expansion, we will continue to invest in the next generation of manufacturing and supply chain resilience."
Results from Pfizer's EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) study showed an 88% reduction in COVID-19-related hospitalization or death from any cause in adults treated with PAXLOVID compared to placebo within five days of symptom onset. PAXLOVID is currently approved or authorized for conditional or emergency use in more than 60 countries across the globe to treat high-risk COVID-19 patients.
To learn more about Pfizer's manufacturing and global supply, visit www.pfizer.com/pgs.
About the 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 of these results was high (p
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 discontinuations 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 are available on clinicaltrials.gov (NCT04960202) and EudraCT (2021-002895-38).
U.S. FDA Emergency Use Authorization Statement
PAXLOVID has not been approved but has been authorized for emergency use by FDA under an EUA, for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS CoV-2 viral testing, and who are at high-risk for progression to severe COVID-19, including hospitalization or death.
The emergency use of PAXLOVID is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner.
AUTHORIZED USE
The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the unapproved product PAXLOVID for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
LIMITATIONS OF AUTHORIZED USE
- PAXLOVID is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19
- PAXLOVID is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19
- PAXLOVID is not authorized for use for longer than 5 consecutive days
PAXLOVID may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which PAXLOVID belongs (i.e., anti-infectives).
PAXLOVID is not approved for any use, including for use for the treatment of COVID-19.
PAXLOVID is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of PAXLOVID under 564(b)(1) of the Food Drug and Cosmetic Act unless the authorization is terminated or revoked sooner.
IMPORTANT SAFETY INFORMATION
PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions (eg, toxic epidermal necrolysis [TEN] or Stevens-Johnson syndrome) to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product.
PAXLOVID is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions:
- Alpha1-adrenoreceptor antagonist: alfuzosin
- Analgesics: pethidine, propoxyphene
- Antianginal: ranolazine
- Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine
- Anti-gout: colchicine
- Antipsychotics: lurasidone, pimozide, clozapine
- Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
- HMG-CoA reductase inhibitors: lovastatin, simvastatin
- PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial hypertension
- Sedative/hypnotics: triazolam, oral midazolam
PAXLOVID is contraindicated with drugs that are potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer:
- Anticancer drugs: apalutamide
- Anticonvulsant: carbamazepine, phenobarbital, phenytoin
- Antimycobacterials: rifampin
- Herbal Products: St. John's Wort (hypericum perforatum)
There are limited clinical data available for PAXLOVID. Serious and unexpected adverse events may occur that have not been previously reported with PAXLOVID use.
Risk of Serious Adverse Reactions Due to Drug Interactions: Initiation of PAXLOVID, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving PAXLOVID, may increase plasma concentrations of medications metabolized by CYP3A. Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of PAXLOVID, respectively. These interactions may lead to:
- Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications
- Clinically significant adverse reactions from greater exposures of PAXLOVID
- Loss of therapeutic effect of PAXLOVID and possible development of viral resistance
Consult Table 1 of the Fact Sheet for Healthcare Providers for clinically significant drug interactions, including contraindicated drugs. Consider the potential for drug interactions prior to and during PAXLOVID therapy; review concomitant medications during PAXLOVID therapy and monitor for the adverse reactions associated with the concomitant medications.
Hypersensitivity reactions have been reported with PAXLOVID including urticaria, angioedema, dyspnea, mild skin eruptions, and pruritus. Cases of anaphylaxis, TEN, and Stevens-Johnson syndrome have also been reported with components of PAXLOVID (refer to NORVIR labeling). If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue PAXLOVID and initiate appropriate medications and/or supportive care.
Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering PAXLOVID to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis.
Because nirmatrelvir is co-administered with ritonavir, there may be a risk ofHIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.
Adverse events in the PAXLOVID group (≥1%) that occurred at a greater frequency (≥5 subject difference) than in the placebo group were dysgeusia (6% and
The following adverse reactions have been identified during post-authorization use of PAXLOVID. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders: Hypersensitivity reactions
Required Reporting for Serious Adverse Events and Medication Errors: The prescribing healthcare provider and/or the provider's designee is/are responsible for mandatory reporting of all serious adverse events and medication errors potentially related to PAXLOVID within 7 calendar days from the healthcare provider's awareness of the event.
Submit adverse event and medication error reports to FDA MedWatch using one of the following methods:
- Online: https://www.fda.gov/medwatch/report.htm
- Complete and submit a postage-paid FDA Form 3500and returning by mail/fax
- Call 1-800-FDA-1088 to request a reporting form
