Pharmaceutical Technology Editors

Pfizer has expanded its voluntary recall to include all lots of varenicline (Chantix) 0.5 mg and 1 mg tablets, according to a Sept. 17, 2021, FDA press release. This recall is due to the presence of unacceptable N-nitroso-varenicline levels.

However, drug shortages for this drug product are a concern. Therefore, FDA has temporarily exercised regulatory flexibility and discretion for the distribution of the Health Canada-approved Apo-Varenicline tablets in the United States by Apotex, a Canadian pharmaceutical company, that contains N-nitroso-varenicline up to FDA’s interim acceptable intake limit. 

This measure is intended to help maintain adequate varenicline supply in the US for the near term. FDA stated in their press release that they won’t object to certain manufacturers distributing varenicline tablets containing N-nitroso-varenicline above FDA’s acceptable intake limit of 37 ng per day but below the interim acceptable intake limit of 185 ng per day until the impurity can be eliminated or reduced to acceptable levels.

Patients taking varenicline from the recalled lots are instructed by FDA to continue taking their current medicine until their pharmacist provides a replacement or their doctor prescribes a different treatment, as they believe the health benefits of stopping smoking outweigh the cancer risk from the nitrosamine impurity in varenicline.

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Pfizer has expanded its voluntary recall to include all lots of varenicline (Chantix), but FDA allows continued distribution of the drug product to continue due to drug shortages. 

Pfizer Expands Varenicline (Chantix) Recall, But Drug Shortages Remain a Concern

Health Canada approved the new drug submission (NDS-CV) for Spikevax (elasomeran mRNA vaccine)—more commonly known as the Moderna COVID-19 vaccine—for active immunization to prevent COVID-19 in individuals 12 years of age and older, according to Moderna’s Sept. 16, 2021, press release.

The NDS-CV for Spikevax was approved based on clinical data from the Phase III COVE study of the Moderna COVID-19 vaccine, which enrolled more than 30,000 participants in the United States. The final analysis of Spikevax showed 93% efficacy , with the efficacy remaining durable through six months after administration of the second dose. In addition, the safety profile was consistent with the Phase III COVE study primary results.

Spikevax was originally authorized in Canada under an interim order for individuals 18 years of age and older, which was granted by Health Canada on Dec. 23, 2020. On Aug. 27, 2021, the interim order authorization for the Moderna COVID-19 vaccine was expanded to include adolescents 12 years of age and older.

“Health Canada’s approval of our COVID-19 vaccine is an important milestone as it is our first full approval for Spikevax,” said Stéphane Bancel, CEO of Moderna, in the company press release. “I would like to thank Health Canada for their hard work throughout the process. I would also like to thank the Government of Canada for the partnership they have built with us and for their confidence in our mRNA platform in addressing the COVID-19 pandemic.”

Health Canada approved the new drug submission for Spikevax—more commonly known as the Moderna COVID-19 vaccine—for active immunization to prevent COVID-19 in individuals 12 years of age and older.

Health Canada Approves Moderna’s COVID-19 Vaccine, Spikevax, for 12 Years & Up

On Sept. 16, 2021, FDA revised the emergency use authorization (EUA) for bamlanivimab and etesevimab (administered together) to 

include emergency use as post-exposure prophylaxis (prevention) for COVID-19

 in patients 12 years of age and older who weigh at least 40 kg and are at high risk for progression to severe COVID-19, including hospitalization or death. Bamlanivimab and etesevimab are monoclonal antibodies (mAbs).

Bamlanivimab and etesevimab (administered together) are now authorized for use after exposure to the SARS-CoV-2 virus in this revision of the EUA. The mAbs are not authorized for pre-exposure prophylaxis to prevent COVID-19 before being exposed to the virus.

These mAbs may only be used when administered together as post-exposure prophylaxis for patients 12 years of age and older weighing at least 40 kg who:

Are at high risk for progression to severe COVID-19, including hospitalization or death

Are not fully vaccinated or who are not expected to have an adequate immune response to complete COVID-19 vaccination

Have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria, per the CDC

Are at high risk of exposure to an individual infected with SARS-CoV-2 in the same institutional setting (such as nursing homes)

In addition, bamlanivimab and etesevimab (administered together) remain authorized for the treatment of mild to moderate COVID-19 in 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.

FDA revised the emergency use authorization for bamlanivimab and etesevimab (administered together) to include emergency use as post-exposure prophylaxis (prevention) for COVID-19.

FDA Revises EUA for Use of Bamlanivimab and Etesevimab for Post-Exposure Prophylaxis Prevention for COVID-19

Moderna released an analysis surrounding several studies on their COVID-19 vaccine on Sept. 15, 2021. In it, the company shared data surrounding the efficacy of the vaccine amidst the Delta variant surge, the risk of breakthrough infections, and the need for booster shots.

According to Moderna, a prospective cohort study of 352,878 recipients found that there was a vaccine effectiveness of 87% against COVID-19 diagnosis and 96% against COVID-19 hospitalization. The study was conducted during the emergence of the Delta variant, which was identified in 47% of cases in fully vaccinated individuals.

Moderna also did an analysis of data provided by CDC on breakthrough infections among individuals who received the vaccine. They found that their COVID-19 vaccine provided 92% efficacy against COVID-19 urgent care or emergency visit at a median of 96 days post-vaccination, and 95% efficacy against hospitalization at a median of 106 days after hospitalization.

In the Coronavirus Efficacy and Safety Study (COVE) study, an analysis comparing individuals vaccinated between July and October of 2020 and December 2020 and March of 2021, 88 breakthrough cases of COVID-19 occurred in the more recently vaccinated group (49.0 cases per 1000 people) compared to 162 cases in the group vaccinated last year (77.1 cases per 1000 people). Moderna believes that the impact of waning immunity provides evidence of the potential benefit of a booster dose of mRNA-1273.

“It is promising to see clinical and real-world evidence adding to the growing body of data on the effectiveness of the Moderna COVID-19 vaccine,” said Stéphane Bancel, CEO of Moderna, in a company press release. “The increased risk of breakthrough infections in COVE study participants who were vaccinated last year compared to more recently illustrates the impact of waning immunity and supports the need for a booster to maintain high levels of protection. We hope these findings are helpful as health authorities and regulators continue to assess strategies for ending this pandemic.”

Moderna’s newest insights include an overall efficacy review, a study on breakthrough infections, and a study on long-term immunity.

Moderna Releases New Clinical Data on COVID-19 Vaccine

FDA announced the reorganization of the agency’s information technology (IT), data management, and cybersecurity function into the new Office of Digital Transformation (ODT) on Sept. 15, 2021. Vid Desai has been appointed as the ODT’s chief information officer.

ODT will function on an agency level and report directly to the FDA commissioner. The goal behind this reorganization, according to the press release, is to transform the way the agency handles IT via improved data and IT competencies. It will streamline various FDA operations by reducing duplicate processes, implementing technological efficiencies through projects that deliver maximum customer benefits, and promoting shared services within agency offices.

The ODT is the latest step in FDA’s Technology Modernization Action Plan from 2019, which laid the groundwork to innovate the agency’s approach to data management and review process. It was followed by the Data Modernization Action Plan in 2021, which further iterated on various streamlining and processing improvements that began in 2019 by identifying high value driver projects for individual centers and the agency.

“Good data management, built into all of our work, ultimately helps us meet and advance the FDA’s mission to ensure safe and effective products for American families,” said Janet Woodcock, acting FDA commissioner, in the press release. “By prioritizing data and information stewardship throughout all of our operations, the American public is better assured of the safety of the nation’s food, drugs, medical devices, and other products that [FDA] regulates in this complex world.”

The new FDA office will reorganize IT, data, and cybersecurity functions to an agency level.

FDA Introduces Office of Digital Transformation

Takeda Pharmaceutical Company announced FDA approval of Exkivity (mobocertinib) for treatment of patients with a specific form of lung cancer on Sept. 15, 2021. Mobocertinib is intended for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

Mobocertinib is an oral tyrosine kinase inhibitor specifically designed to selectively target EGFR exon 20 insertion mutations. FDA previously granted it orphan drug designation, breakthrough therapy designation, and fast track designation.

Per the terms of the approval, Exon 20 insertion mutations must be detected by an FDA-approved test. At the same time as mobocertinib was approved, Thermo Fisher Scientific’s Oncomine Dx Target Test was approved. This will serve as a companion diagnostic designed to identify NSCLC patients with EGFR exon 20 insertions.

“The approval of EXKIVITY introduces a new and effective treatment option for patients with EGFR [exon 20] insertion+ NSCLC, fulfilling an urgent need for this difficult-to-treat cancer,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda, in a company press release. “EXKIVITY is the first and only oral therapy specifically designed to target EGFR [exon 20] insertions, and we are particularly encouraged by the duration of the responses observed with a median of approximately 1.5 years. This approval milestone reinforces our commitment to meeting the needs of underserved patient populations within the oncology community.”

Takeda’s Exkivity (mobocertinib) was approved by FDA for the treatment of patients with lung cancer.