Jennifer Barrett

Moderna announced it is seeking full FDA approval for its COVID-19 vaccine mRNA-1273.

In a statement released on Tuesday, the company said it has initiated the rolling submission process for the biologics license application (BLA) and will continue to submit data from its phase 3 study to support the application for use of the vaccine in individuals 18 years and older. Once the rolling BLA submission process is completed, the FDA will notify Moderna when it is formally accepted for review.1

A Timeline of Key Regulatory and Clinical Updates

FDA authorized Moderna’s vaccine for emergency use

 based on a data analysis from the phase 3 COVE study and a primary efficacy analysis conducted on 196 cases which indicated a vaccine efficacy rate of 94.1%.

In February 2021, Moderna completes manufacturing of clinical trial material for its variant-specific vaccine candidate, mRNA-1273.351, against the SARS-CoV-2 variant known as B.1.351 and has shipped doses to the National Institutes of Health for the phase 1 clinical trial.2

In an amendment to the ongoing phase 2 clinical study, the first participants were dosed with the company’s modified COVID-19 vaccines in March to evaluate booster vaccine candidates.3

 demonstrated antibody persistence through 6 months following the second dose of the vaccine.4

In May, Moderna reported initial data from its phase 2 study showing that a single 50 µg dose of mRNA-1273 or mRNA-1273.351 given as a booster increased neutralizing antibody titer responses against SARS-CoV-2 and variants B.1.351 and P.1.5

On May 25, Moderna released data from its 

, demonstrating the safety and efficacy of mRNA-1273 in adolescents aged 12 to <18 years. Moderna announced plans to seek authorization for this age group in June.

 of its COVID-19 vaccine, BNT162b2, for use in individuals aged 17 years and older.

This article was originally published on Drug Topics®.

Moderna Announces Initiation of Rolling Submission of Biologics License Application (BLA) with U.S. FDA for the Moderna COVID-19 Vaccine. News Release. Moderna; June 1, 2021. Accessed June 1, 2021. 

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-initiation-rolling-submission-biologics

Moderna Announces it has Shipped Variant-Specific Vaccine Candidate, mRNA-1273.351, to NIH for Clinical Study. News Release. Moderna; February 24, 2021. Accessed June 1, 2021. 

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-it-has-shipped-variant-specific-vaccine

Moderna Announces First Participants Dosed in Study Evaluating COVID-19 Booster Vaccine Candidates. News Release. Moderna; March 10, 2021. Accessed June 1, 2021. 

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-first-participants-dosed-study-evaluating

Doria-Rose N, Suthar MS, Makowski M, et al. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for COVID-19. 

 April 6, 2021. Doi: 10.1056/NEJMc2103916

Moderna Announces Positive Initial Booster Data Against SARS-CoV-2 Variants of Concern. News Release. Moderna; May 5, 2021. Accessed June 1, 2021. 

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-initial-booster-data-against-sars-cov

Articles

Moderna has initiated the rolling submission process for the biologics license application for its COVID-19 vaccine mRNA-1273.

Submission Process for FDA Approval for Moderna COVID-19 Vaccine Begins

In the session, which was presented virtually on May 11, Theresa Schmidt, vice president, Discern Health, and Kimberly Westrich, vice president, Health Services Research, National Pharmaceutical Council, discussed the findings from a systematic review assessing the effects of SDM and PtDAs in a broad range of settings.

Prior experience shows that SDM can improve both quality and experience, according to Westrich. This is because SDM has a number of patient-centered benefits, such as increasing patient satisfaction and reducing decisional conflict. Many stakeholders also assume that SDM will reduce health care costs, especially as some interventions may help patients elect more appropriate care and promote treatment adherence.

The systematic review aimed to provide a comprehensive understanding of the existing body of evidence around SDM outcomes.

Schmidt explained how the research team defined both SDM and PtDA in literature selection. SDM is defined as the process by which clinicians work with patients to explore care choices, benefits and risks, goals and preferences, and jointly make informed care decisions. PtDAs are defined as evidence-based tools designed to educate patients; this can include paper handouts, videos, or web-based platforms. Although PtDAs can be used in conjunction with SDM, “on their own they don’t count as SDM,” Schmidt said.

Overall, SDM must include collaboration between the patient and provider to make decisions, she added.

For the review, the investigators searched PubMed for articles relating to SDM and PtDAs that reported on cost and utilization outcomes. They focused on articles published between 2010 and 2019.

Outcomes were classified into 3 main categories:

Cost: Includes component costs and total cost of care

Utilization: Resource-intensive services such as cardiac screening or discharge to high-cost settings

Prevention-related care: Outcomes involving a process that could prevent future adverse outcomes or utilization, such as end-of-life planning/hospice, cancer screening, or mental health-related utilization

According to Schmidt, the majority of the articles showed a favorable decrease in cost and utilization, and increase in prevention-related care. However, there were mixed findings, indicating that SDM and PtDAs do not always lead to these outcomes.

“While the majority of the articles did present favorable outcomes, a greater majority assessed at least 1 relevant outcome where no significant difference was observed,” Schmidt explained. This is likely because articles often included multiple outcomes.

One of the favorable outcomes that appeared to be impacted was medication adherence. Nine of the 12 studies that measured adherence showed outcomes with favorable increases, according to Schmidt. Eight studies showed no significant difference.

“Adoption of [SDM] can lead to a greater potential patient-provider bond,” Schmidt said. She added that informed patients who are engaged in choosing their own treatment are more likely to have a better understanding of what to expect and less surprised by adverse effects, and therefore more likely to adhere to their medications.

In the context of value-based care, Westrich explained that the mixed results suggest that these interventions may be critical for patient-centered care, but will not always lead to reduced care. However, this does not mean that they do not add value, she said. SDM can increase patient satisfaction and knowledge, reduce decisional conflict, and improve overall experience and outcomes.

“Our results reinforce the value of these interventions for improving medication adherence,” Westrich said.

Although SDM may not be a panacea for reducing health care costs, implementing these interventions can provide value in other areas and still have the potential to reduce costs and utilization.

This article was originally published on 

Schmidt T, Westrich K. The impact of shared decision-making on cost and utilization and implications for value-based care. 2021 Pharmacy Quality Alliance Annual Meeting; May 11-17, 2021; virtual. Accessed May 12, 2021.

Shared decision-making (SDM) and patient decision aids (PtDAs) can lower health care costs, lower utilization, and increase prevention-related care; however, these outcomes are not always guaranteed, according to the results of a recent study presented during the 2021 Pharmacy Quality Alliance Annual Meeting.

Reducing Health Care Costs and Utilization with Shared Decision-Making

Results of a new study suggest that COVID-19 messenger RNA (mRNA) vaccines are immunogenic in pregnant and lactating women, including against viral variants.1

It is known that pregnant women are at an increased risk of morbidity and mortality from COVID-19, but there is currently limited data on COVID-19 vaccine safety and efficacy in this population.

, investigated the immunogenicity in 103 pregnant and lactating individuals aged 18 to 45 years who received either the Pfizer of Moderna COVID-19 vaccines. Overall, 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received a COVID-19 mRNA vaccine and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection were enrolled in the study.

The investigators from Beth Israel Deaconess Medical Center (BIDMC) reported similar levels of vaccine-induced antibody function and T cell responses in all non-pregnant, pregnant, and lactating women after the second dose. Moreover, both pregnant and non-pregnant women who received the vaccines developed cross-reactive immune responses against the COVID-19 variants B.1.1.7 and B.1.351.

“The COVID-19 mRNA vaccines raised robust immune responses in pregnant, lactating, and non-pregnant non-lactating women,” said senior corresponding author, Dan H. Barouch, MD, PhD, director of the Center for Virology and Vaccine Research at BIDMC.

 “Additionally, the vaccine-elicited antibody responses were greater than antibody responses seen after COVID-19 infections. These findings add to the emerging data that support the use of these vaccines in pregnant and lactating women.”

According to the further analysis, vaccination also elicited binding and neutralizing antibodies in breast milk, although immunoglobulin A responses were low in breast milk, with the exception of early breast milk from participants receiving the vaccine during pregnancy. Investigators also detected binding and neutralizing antibodies in infant cord blood, suggesting efficient transplacental transfer of maternal antibodies.

“The results of this study complement these studies by demonstrating neutralizing antibodies in both cord blood and breast milk, suggesting the possibility that newborns may be protected by maternal vaccination,” the investigators wrote.

Collier, AY. McMahan K, Yu J. Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA. Published online May 13, 2021. 10.1001/jama.2021.7563

COVID-19 mRNA Vaccines are Immunogenic in Pregnant and Lactating Women, Including Against Viral Variants. News Release. Beth Israel Deaconess Medical Center; May 13, 2021. Accessed May 14, 2021. 

https://www.bidmc.org/about-bidmc/news/2021/05/covid-19-mrna-vaccines-immunogenic-pregnant-lactating-women

A new study, which was published in JAMA, investigated the immunogenicity in 103 pregnant and lactating individuals aged 18 to 45 years who received either the Pfizer of Moderna COVID-19 vaccines.

Recent Study on COVID-19 Vaccine Immunogenicity in Pregnant, Lactating Women

Officials with the FDA have granted accelerated approval for GlaxoSmithKline’s dostarlimab-gxly (Jemperli; GlaxoSmithKline) for women with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer.

This indication is approved under accelerated approval based on tumor response rate and durability of response.

Dostarlimab is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. It is also being investigated as a monotherapy and in combination regimens for women with recurrent or primary advanced endometrial cancer stage 3 or 4 non-mucinous epithelial ovarian cancer for patients with advanced solid tumors or metastatic cancer.

The approval is based on results from the ongoing phase 1 GARNET trial, which includes the largest dataset to date evaluating anti-PD-1 antibody as monotherapy treatment in women with endometrial cancer. Patients in the trial received 500 mg of dostarlimab as an intravenous infusion once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression or unacceptable toxicity.

The primary end points in the trial were overall response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review. According to the results, dostarlimab demonstrated an ORR of 42.3% (95% CI; 30.6-54.6) with a complete response rate of 12.7% and partial response rate of 29.6% among the 71 evaluable patients with dMMR advanced or recurrent endometrial cancer who had progressed on or after treatment with a platinum-containing regimen. Of those that responded, 93.3% demonstrated a DOR of 6 months or more. After a median follow-up of 14.1 months, the median DOR was not reached.

Among the 104 patients evaluable for safety, the most commonly reported adverse effects were fatigue/asthenia, nausea, diarrhea, anemia, and constipation.

“The approval of dostarlimab has the potential to change the way we’ve been treating dMMR advanced or recurrent endometrial cancer after standard platinum-based chemotherapy, especially given the overall response rate and durability of response that we saw in the GARNET trial,” study investigator Jubilee Brown, MD, professor and division director of gynecologic oncology at Levine Cancer Institute, Atrium Health, said in a statement.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

1. FDA grants accelerated approval for GSK’s JEMPERLI (dostarlimab-gxly) for women with recurrent or advanced dMMR endometrial cancer. News release. GlaxoSmithKline; April 22, 2021. Accessed April 22, 2021. 

https://www.gsk.com/en-gb/media/press-releases/fda-grants-accelerated-approval-for-gsk-s-jemperli-dostarlimab-gxly-for-women-with-recurrent-or-advanced-dmmr-endometrial-cancer/

FDA Grants Accelerated Approval to Dostarlimab for Advanced dMMR Endometrial Cancer

US health officials are recommending a pause in the administration of the single-dose Johnson & Johnson COVID-19 vaccine following 6 reports of a rare and severe type of blood clot, according to a joint statement issued on Tuesday by the CDC and FDA.

The FDA will further investigate the cases, in which a blood clot called cerebral venous sinus thrombosis (CVST) was seen in combination with low levels of blood platelets, called thrombocytopenia. The CDC will also convene a meeting of the Advisory Committee on Immunization Practices (ACIP) on Wednesday to review the cases and assess their potential significance.

In a media briefing held on Tuesday, Peter Marks, MD, PhD, director of the FDA Center for Biologics Evaluation and Research; Janet Woodcock, MD, acting commissioner of the FDA; and Anne Schuchat, MD, principal deputy director of the CDC, discussed the details regarding the recommendation.

"We're recommending this pause while we work together to fully understand these events and also while we get information out to health care providers and [vaccine] recipients," Woodcock said in the briefing.

More than 6 millon doses of the Johnson & Johnson vaccine have been administered so far. Reports of these types of blood clots following the vaccine include 6 cases, all of which occurred in women between the ages of 18 and 48. Symptoms developed 6 to 13 days after vaccination. Of the clots seen in the United States, 1 case was fatal and 1 patient is in critical condition.

"Right now, these events seem to be extremely rare," Marks emphasized. "That said, COVID-19 vaccine safety is a top priority for the federal government." Marks added that the FDA will revise the fact sheet for health care providers and recipients to include this adverse event information. Health care providers who observe patients presenting to them with either low blood platelet counts or blood clots should establish whether or not the patient has recently been vaccinated, he said.

For individuals who have already received the Johnson & Johnson vaccine, Schuchat noted that the risk is very low for those who received the vaccine at least 1 month ago. Individuals who received the vaccine in the last couple of weeks should be aware of any symptoms.

However, Schuchat emphasized that these symptoms are different from the mild flu-like symptoms that many recipients experience in the couple of days following vaccination. Individuals who receive the Johnson & Johnson vaccine and develop severe headache, abdominal pain, leg pain, or shortness of breath within 3 weeks after vaccination should contact their health care providers.

No cases of clotting events with low platelet counts have been seen with the Moderna or Pfizer-BioNTech COVID-19 vaccines.

The ACIP will convene tomorrow to review the data on these initial cases to determine next steps.

This article was originally published on Drug Topics®

1. Joint CDC and FDA Statement on Johnson & Johnson COVID-19. News Release. FDA, CDC; April 13, 2021. Accessed April 13, 2021. 

https://www.prnewswire.com/news-releases/joint-cdc-and-fda-statement-on-johnson--johnson-covid-19-vaccine-301267526.html

The CDC and FDA will further investigate the reports of blood clots following administration of the vaccine.

FDA, CDC Recommend Temporary Pause for Johnson & Johnson COVID-19 Vaccine

President Biden today promised that the federal government will have enough doses of the COVID-19 vaccine to vaccinate approximately 300 million Americans by the end of May, which is 2 months earlier than anticipated.1,2

The news follows an agreement between the Biden administration and Merck that will allow the company to assist in manufacturing Johnson & Johnson’s recently-authorized 1-dose vaccine.3,4 Earlier today, Press Secretary Jen Psaki said that the US government will invoke the Defense Production Act to equip 2 Merck facilities to the standards necessary to safely manufacture the vaccine.4 According to a Merck press release, the company will use its US facilities to produce drug substance, formulate, and fill vials of the vaccine for distribution.3

FDA approved Johnson & Johnson’s vaccine

 for emergency use on February 27, making it the third safe and highly effective COVID-19 vaccine to be approved for use in the United States.

FDA Analysis of Johnson & Johnson COVID-19 Vaccine Confirms Safety, Efficacy

Biden also announced during his remarks that he will direct all states to prioritize vaccinating teachers, challenging states to administer at least 1 dose of the vaccine to all educators by the end of March. Biden said that the government will provide the doses directly through its pharmacy program. Teachers will be able to sign up directly through participating retail pharmacies in their local area, according to the administration.1,2

, the administration has sent millions of vaccine to more pharmacies across the country. This week, more than 800,000 doses of the Johnson & Johnson vaccine will also be distributed to pharmacies.1,2

Starting next week, the Biden administration also announced that the federal government was increasing the supply of Moderna and Pfizer vaccines to states to 15.2 million doses per week, up from 14.5 million previously. Furthermore, states are also receiving 2.8 million of the Johnson & Johnson vaccine this week.3

1. White House Press Briefing. President Biden Delivers Remarks on the Ongoing COVID-19 Pandemic. March 2, 2021.

2. Miller Z, Johnson LA, Lemire J. Biden vows enough vaccine for all US adults by end of May. Published March 2, 2021. Accessed March 2, 2021. 

https://apnews.com/article/merck-help-make-johnson-johnson-vaccine-9ca6f1f4c502b095531926a53abe7262

3. The White House. Press Briefing by Press Secretary Jen Psaki, March 2, 2021. 

https://www.whitehouse.gov/briefing-room/press-briefings/2021/03/02/press-briefing-by-press-secretary-jen-psaki-march-2-2021/

4. Merck to Help Produce Johnson & Johnson’s COVID-19 Vaccine; BARDA to Provide Merck With Funding to Expand Merck’s Manufacturing Capacity for COVID-19 Vaccines and Medicines. News release. Merck; March 2, 2021. Accessed March 2, 2021. 

https://www.merck.com/news/merck-to-help-produce-johnson-barda-to-provide-merck-with-funding-to-expand-mercks-manufacturing-capacity-for-covid-19-vaccines-and-medicines/

President Biden promised that the federal government will have enough vaccine supply to vaccinate approximately 300 million Americans by the end of May.