Pfizer, Moderna, J&J Plan COVID-19 Vaccine Supply Increase; Evaluating Variants

Pfizer/BioNTech, Moderna, and Johnson & Johnson (J&J) have detail plans to increase supply of their respective COVID-19 vaccines to the US. The companies have also provided updates on variant studies.

Supply update: Pfizer/BioNTech

Pfizer says it expects to increase the number of vaccine doses available for shipment to the US from approximately 4 million to 5 million doses per week at the beginning of February (February 2021) to more than 13 million doses per week by the middle of March (March 2021). John Young, Pfizer’s Chief Business Officer, provided the update in written testimony on February 23, 2021 before the US House Committee on Energy and Commerce Oversight and Investigations Subcommitte.

The company says it is on track to make 120 million doses available for shipment by the end of March (March 2021) and an additional 80 million doses by the end of May (May 2021). Pfizer anticipates all 300 million contracted doses with the US government will be made available for shipment by the end of July (July 2021), enabling the vaccination of up to 150 million individuals in the US.

Earlier this month (February 2021), the US government purchased an additional 100 million doses of the COVID-19 vaccine from Pfizer and BioNTech to bring the total amount of doses purchased by the US government to 300 million. As of February 17, 2020, the company had shipped approximately 40 million doses of its COVID-19 vaccine to the US.

Pfizer’s facility in Kalamazoo, Michigan remains the primary manufacturing site of the vaccine in the US. The company has also made investments at its other US manufacturing sites, including Saint Louis, Missouri; Andover, Massachusetts; Kalamazoo, Michigan; and Pleasant Prairie, Wisconsin. In addition, the company added new lines at its site in McPherson, Kansas, started lipid production at its site in Groton, Connecticut; and added contract manufacturers.

Pfizer and BioNTech formed recent agreements for the supply of lipids for the vaccine. This week (February 25, 2021), AMRI was chosen to support the development and manufacture of lipid excipients for the Pfizer-BioNTech COVID-19 vaccine. For the past several months (as reported on February 25, 2021), AMRI has been providing development, scale-up and manufacturing services at a number of its global R&D and production sites to deliver capacity for the lipid excipient supply for the vaccine.Earlier this month (February 2021), Evonik, a specialty and fine chemicals producer, announced it is expanding its specialty lipids produced at its Hanau and Dossenheim sites in Germany as part of a strategic partnership with BioNTech.

Separately, with respect to shipping the vaccine, the US Food and Drug Administration announced on February 25, 2021 that it is allowing undiluted frozen vials of the Pfizer/BioNTech COVID-19 vaccine to be transported and stored at conventional temperatures commonly found in pharmaceutical freezers for a period of up to two weeks. This reflects an alternative to the preferred storage of the undiluted vials in an ultra-low temperature freezer between -80 ºC to -60 ºC (-112 ºF to -76 ºF). The companies submitted stability data generated on batches manufactured over the past nine months of COVID-19 vaccine development, from the batches that supplied the earliest clinical trials through the commercial scale batches currently in production. These data also will be submitted to global regulatory agencies within the next few weeks (as reported on February 19, 2021).

Supply update: Moderna

Moderna is on track to meet its commitment to deliver 100 million doses of its COVID-19 vaccine to the US government by the end of March (March 2021). The company is aiming to double its deliveries by April (April 2021) to more than 40 million doses per month. To date, Moderna has delivered over 55 million doses of its vaccine to the US. Dr. Stephen Hoge, President of Moderna provided the update in testimony on February 23, 2021 before the House Energy and Commerce Committee Subcommittee on Oversight & Investigations.

The US government purchased an additional 100 million doses of Moderna’s COVID-19 vaccine earlier this month (February 2021) to bring the total amount of doses purchased to 300 million. Moderna says it is aiming to deliver a second hundred million doses by the end of May (May 2021) and a third hundred million doses by the end of July (July 2021).

Since the end of 2020, Moderna has doubled its monthly deliveries of vaccine doses to the US government, and the company is working to double them again by April (April 2021) to more than 40 million doses per month. All US supply for Moderna’s vaccine comes from its dedicated supply chain in the US.

Moderna reported it is increasing its base plan for 2021 manufacturing from 600 million doses to 700 million doses globally. Moderna is exploring other approaches to potentially improve throughput and is working to further optimize its operations to potentially deliver up to 1 billion doses in fiscal year 2021.

The company has shipped approximately 60 million doses globally, including approximately 55 million doses shipped to the US government to date (as reported on February 24, 2021) and the first approximately 4 million doses shipped from its ex-US supply chain. This ex-US supply chain was established one quarter behind the US supply chain and is in the process of ramping up.

Moderna announced it is making new capital investments to increase capacity at its owned and partnered manufacturing facilities, which it expects will increase global 2022 capacity to approximately 1.4 billion doses of its COVID-19 vaccine, assuming a 100-μg dose. The investments will enable additional production of Moderna’s current COVID-19 vaccine and provide flexibility in addressing production of potential vaccine boosters that may be needed to address emerging variants of SARS-CoV-2, the virus that causes COVID-19.

The 2022 capacity of up to 1.4 billion doses reflects an assumption of a 100-μg dose. The total 2022 supply will depend on the mix between the authorized COVID-19 Vaccine at 100 μg and the dose level authorized for a booster. In the event that the company dedicates its entire 2022 capacity to a 50-μg boost, Moderna could supply up to 2.8 billion doses in fiscal year 2022. The maximum output will be determined as the company more fully develops its booster product strategy.

The company has already begun adding this capacity at its owned and partnered manufacturing facilities. Given a six- to nine-month timeframe to add capacity and an additional timeframe to permit regulatory validation and ramp-up, it is estimated that up to 12 months may be necessary before the additional production is available.

Separately, Takeda is developing Moderna’s COVID-19 vaccine in Japan. The company will import and distribute 50 million doses of Moderna’s COVID-19 vaccine candidate, named TAK-919 in Japan, as part of a joint partnership with Moderna and the Government of Japan’s Ministry of Health Labour and Welfare. Takeda intends to start distributing TAK-919 in the first half of 2021.

Earlier this month (February 2021), Takeda completed enrollment in a Phase I/II immunogenicity and safety study of TAK-919 in Japan. Results from the TAK-919 study are expected in the first half of 2021.

Supply update: Johnson & Johnson

Assuming regulatory approvals for its COVID-19 vaccine relating to the company’s manufacturing processes, J&J is planning for the immediate shipment to deliver enough single-doses of its COVID-19 vaccine by the end of March (March 2021) to enable the vaccination of more than 20 million individuals in the US. Dr. Richard Nettles, Vice President of US Medical Affairs of Janssen Infectious Diseases and Vaccines at J&J provided the update in testimony on February 23, 2021 before the House Energy and Commerce Committee Subcommittee on Oversight & Investigations.

The company says it is confident in its plans to deliver 100 million single-dose COVID-19 vaccines to the US during the first half of 2021 and that it is continuing to partner with the US government to explore all options to accelerate delivery.

Earlier this month (February 2021), J&J submitted an application for conditional marketing authorization to the European Medicines Agency and a request to the US Food and Drug Administration (FDA) for emergency use authorization (EUA) for its single-dose COVID-19 vaccine candidate. An advisory committee of the FDA is meeting on February 26, 2021 to review the EUA request.

If an EUA is issued, the US government anticipates allocating 3 million to 4 million doses of J&J’s COVID-19 vaccine next week (as reported on February 24, 2021). The US government is working with J&J to accelerate the pace and timeframe by which the company can deliver the full 100 million doses, which is required by contract by the end of June (June 2021).

J&J has entered into an agreement with Sanofi in which Sanofi will provide manufacturing support for J&J’s COVID-19 vaccine.

Pfizer/BioNTech, Moderna, J&J advance studies against variants

Pfizer/BioNTech. Pfizer and BioNTech have begun an evaluation of the safety and immunogenicity of a third dose of their COVID-19 vaccine to understand the effect of a booster on immunity against COVID-19 caused by the circulating and potential newly emerging SARS-CoV-2 variants.

The study will draw upon participants from the Phase I study in the US who will be offered the opportunity to receive a 30-µg booster of the current vaccine six to 12 months after receiving their initial two-dose regimen. The study is part of the companies’ clinical development strategy to determine the effectiveness of a third dose against evolving variants.

Separately, in order to be prepared for any potential future strain changes, Pfizer and BioNTech are in ongoing discussions with regulatory authorities, including the FDA and the European Medicines Agency, regarding a registration-enabling clinical study to evaluate a variant-specific vaccine having a modified mRNA sequence.

Based on in-vitro studies conducted to date (as reported on February 25, 2021) and observations from real-world evidence, the Pfizer and BioNTech have not observed changes to neutralizing antibody levels that would predict a significant reduction in protection provided by two doses of their COVID-19 vaccine.

Separately, Pfizer and BioNTech are advancing studies of their COVID-19 vaccine in pregnant women and children have dosed the first subjects in a global Phase II/III study to evaluate their COVID-19 vaccine in preventing COVID-19 in healthy pregnant women 18 years of age and older.

The companies expect to start additional studies in children between the ages of 5 and 11 over the next couple of months (as reported on February 18, 2021), and in children younger than 5 later in 2021. Safety and efficacy in subjects 12 to 15 years of age are already being evaluated in a global Phase III study, and the relevant data are planned to be submitted to the regulatory authorities in the second quarter of 2021. The companies are also planning studies to further evaluate the vaccine in people with compromised immune systems.

Moderna. Moderna has completed the manufacturing of clinical trial material for its variant-specific vaccine candidate, mRNA-1273.351, against the SARS-CoV-2 variant first identified in the Republic of South Africa and has shipped doses to the US National Institutes of Health (NIH) for a Phase I clinical trial that will be led and funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).

While initial data confirms that the Moderna’s COVID-19 vaccine provides neutralizing activity against variants of concern, Moderna is pursuing two strategies against these variants, subject to FDA review: (1) the company is evaluating booster doses of the vaccine to increase neutralizing immunity against the variants of concern and plans to evaluate three approaches to boosting; and (2) the company plans to evaluate mRNA-1273.351 and mRNA-1273.211 as a primary vaccination series for those who are seronegative. These candidates will be evaluated in a two-dose series at the 100-µg dose level and lower.

NIAID, part of the NIH, will conduct a Phase I clinical trial to determine if mRNA-1273.351 can boost immunity against the variants of concern. Moderna will provide doses of mRNA-1273.351 to the NIH. NIAID will initiate this study after receiving safe-to-proceed authorization from the FDA. NIAID will provide additional information when the trial begins. In parallel, Moderna will be conducting its own clinical studies to support regulatory filings for any booster vaccine or updated primary vaccine.

Johnson & Johnson. Last month (January 2021), J&J announced that its single-dose COVID-19 vaccine met the study’s primary and key secondary endpoints. Importantly, this result was achieved across emerging variants, including the virulent B.1.351 variant first observed in South Africa, and the P2 variant first observed in Brazil.

Source: US Government (Pfizer), US Government (Moderna), US Government (J&J), Press Briefing by White House, Pfizer (supply update), BioNTech (supply update), Pfizer (freezer), Pfizer (pregnancy trial), BioNTech (freezer) and BioNTech (pregnancy trial), FDA (freezer), Moderna (investment), Moderna (variants), Takeda, and AMRI

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