COVID-19 updates
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We published COVID-19 Update #58 on 14 December 2020, highlighting the Emergency Use Authorization (EUA) for Pfizer-BioNTech’s COVID‐19 Vaccine for the prevention of COVID-19 for individuals 16 years of age and older. Vaccine Fact Sheets are available for Healthcare Providers and Vaccine Recipients/Caregivers. The CDC's Advisory Committee on Immunization Practices (ACIP) voted 11-0, with three recusals to recommend use of Pfizer-BioNTech’s vaccine on 12/12/2020 for patients 16 and older. ACIP had a unanimous vote to include the vaccine in 2021 immunization schedules.
Four days later, COVID-19 Update # 59 provided a link to an FDA review of clinical data for Moderna’s COVID-19 vaccine where evidence supported 94.1% efficacy and no major safety concerns. An age specific breakdown of efficacy found the vaccine to be 95.6% efficacious in patients under 65 and 84.6% efficacious in those 65 and older. Efficacy was consistent across race and ethnicity demographics. The most common ADR were mild-to-moderate pain at the injection site, fatigue, headache, muscle pain, joint pain and chills. Three vaccine recipients and one placebo recipient experienced Bell’s palsy, so the FDA has recommended ongoing monitoring for Bell's once widespread vaccination begins. On 12/17/2020, the FDA’s Vaccines and Related Biological Products Advisory Committee voted 20-0, with one abstention to recommend an emergency use authorization for Moderna’s mRNA-1273 as prophylaxis for COVID-19 infections for patients 18 years and older. Also on that day we notified subscribers that some vials of the Pfizer-BioNTech COVID-19 vaccine contain overfill of the vaccine. The FDA advised it is acceptable to use each additional full dose in the vials. But partial doses from different vials, should not be combined for a full dose, since the vials are preservative free. On Monday, in COVID-19 #60, we noted that on 12/18/2020, the FDA granted an Emergency Use Authorization (EUA) for Moderna’s COVID‐19 Vaccine for the prevention of COVID-19 for individuals 18 years of age and older. Vaccine Fact Sheets are available for Healthcare Providers and Vaccine Recipients/Caregivers. The CDC's Advisory Committee on Immunization Practices (ACIP) voted 11-0, with three recusals to recommend use of Moderna’s vaccine on 12/19/2020. The CDC approved use of any full extra doses contained in the vials. The CDC has provided eight point interim clinical considerations for the Pfizer-BioNTech and Moderna COVID-19 vaccines. COVID-19 Vaccines
An FDA review of clinical data for Moderna’s COVID-19 vaccine found evidence supporting 94.1% efficacy and no major safety concerns. An age specific breakdown of efficacy found the vaccine to be 95.6% efficacious in patients under 65 and 84.6% efficacious in those 65 and older. Efficacy was consistent across race and ethnicity demographics. The most common ADR were mild-to-moderate pain at the injection site, fatigue, headache, muscle pain, joint pain and chills. Three vaccine recipients and one placebo recipient experienced Bell’s palsy, so the FDA has recommended ongoing monitoring for Bell's once widespread vaccination begins. On 12/17/2020, the FDA’s Vaccines and Related Biological Products Advisory Committee voted 20-0, with one abstention to recommend an emergency use authorization for mRNA-1273 as prophylaxis for COVID-19 infections for patients 18 years and older. On 12/18/2020, the FDA granted an Emergency Use Authorization (EUA) for Moderna’s COVID‐19 Vaccine for the prevention of COVID-19 for individuals 18 years of age and older. Vaccine Fact Sheets are available for Healthcare Providers and Vaccine Recipients/Caregivers. The CDC's Advisory Committee on Immunization Practices (ACIP) voted 11-0, with three recusals to recommend use of Moderna’s vaccine on 12/19/2020. The CDC approved use of any full extra doses contained in the vials. The CDC has provided interim clinical considerations for the Pfizer-BioNTech and Moderna COVID-19 vaccines.
Johnson & Johnson announced completion of enrollment in the 45,000 patient, Phase III, ENSEMBLE trial in mid-December 2020. J&J estimates interim data to be available at the end of January 2021 and a request for an Emergency Use Authorization in February 2021. COVID-19 Anti-Inflammatories Mesoblast announced interim data from 180 patients enrolled in a 30-day, 300 patient, Phase III trial (NCT04371393), where treatment with remestemcel-L did not reduce all-cause mortality compared to placebo in ventilator-dependent patients with moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19. The Data Safety Monitoring Board (DSMB) estimated the trial is unlikely to achieve a 43% reduction in mortality at the target enrollment. The DSMB recommended the trial be completed with the currently enrolled 223 patients. No safety concerns were detected in the interim analysis. COVID-19 Vaccines
An FDA review of clinical data for Moderna’s COVID-19 vaccine found evidence supported 94.1% efficacy and no major safety concerns. An age specific breakdown of efficacy found the vaccine to be 95.6% efficacious in patients under 65 and 84.6% efficacious in those 65 and older. Efficacy was consistent across race and ethnicity demographics. The most common ADR were mild-to-moderate pain at the injection site, fatigue, headache, muscle pain, joint pain and chills. Three vaccine recipients and one placebo recipient experienced Bell’s palsy, so the FDA has recommended ongoing monitoring for Bell's once widespread vaccination begins. On 12/17/2020, the FDA’s Vaccines and Related Biological Products Advisory Committee voted 20-0, with one abstention to recommend an emergency use authorization for mRNA-1273 as prophylaxis for COVID-19 infections for patients 18 years and older. Some vials of the Pfizer-BioNTech COVID-19 vaccine contain overfill of the vaccine. The FDA has advised it is acceptable to use each additional full dose in the vials. But partial doses from different vials, should not be combined for a full dose, since the vials are preservative free. The American College of Obstetricians and Gynecologists (ACOG) recommends the Pfizer-BioNTech COVID-19 vaccine should not be withheld from pregnant or lactating women who meet criteria for vaccination based on ACIP-recommended priority groups. A discussion with the patient of the vaccine should include the potential for adverse effects, hand washing and wearing a mask. Patients should be educated that an mRNA vaccine is not a live virus vaccine and no adjuvant is used in the Pfizer-BioNTech COVID-19 vaccine. The mRNA vaccines do not enter the nucleus and do not alter human DNA in vaccine recipients, so these types of vaccines cannot cause any genetic changes. The CDC also discusses mRNA vaccines on a dedicated web page. ACOG recommends the patient’s decision on whether to receive the vaccine should be supported. The CDC has provided interim clinical considerations for the Pfizer-BioNTech COVID-19 vaccine.
Curevac initiated the 36,500 patient, Phase IIb/III, HERALD trial (NCT04652102) in December, to evaluate its mRNA COVID-19 vaccine, CVnCoV, for the prevention of COVID-19 in Europe and Latin America. COVID-19 Antibodies Interim data from 275 patients enrolled in a 6,420 patient, Phase II/III trial (NCT04425629), where treatment with REGN-COV2 lowered viral levels through day 7 to a greater extent at increasing viral loads. The monoclonal antibody appeared to be more efficacious in patients that had not produced antibodies and/or had higher viral loads. Treatment with REGN-COV2 reduced COVID-19 related medical visits compared to placebo (3% vs 6%). COVID-19 Anti-Inflammatories In the NIAID sponsored 29-day, 1,033 patient, Phase III, ACTT 2 trial (NCT04401579), baricitinib added to remdesivir reduced the time to recovery by one day (7 vs 8 days) compared to remdesivir alone in hospitalized patients with moderate to severe COVID-19. The largest effect was seen in patients receiving high-flow oxygen or non-invasive ventilation (10 vs 18 days) NIH did not find enough evidence to recommend for or against use of baricitinib in combination with remdesivir for the treatment of hospitalized patients in cases where corticosteroids can be used instead. If corticosteroids cannot be used NIH recommends use of baricitinib plus remdesivir in hospitalized, nonintubated patients who require oxygen supplementation. NIH found insufficient evidence to support the use of baricitinib in patients already receiving corticosteroids. Except for clinical trials, NIH does not recommend the use of baricitinib without remdesivir. On 12/11/2020, the FDA granted an Emergency Use Authorization (EUA) for Pfizer-BioNTech’s COVID‐19 Vaccine for the prevention of COVID-19 for individuals 16 years of age and older. Vaccine Fact Sheets are available for Healthcare Providers and Vaccine Recipients/Caregivers. The CDC's Advisory Committee on Immunization Practices (ACIP) voted 11-0, with three recusals to recommend use of Pfizer-BioNTech’s vaccine on 12/12/2020. ACIP also had a unanimous vote to include the vaccine in 2021 immunization schedules. The committee noted there are little data on vaccine outcomes in patients who are pregnant, lactating, immunocompromised, or have severe allergies. The CDC will offer guidance for use of the vaccine in these groups before the end of the year. The CDC officially accepted ACIP’s recommendation to use Pfizer’s COVID-19 vaccine in people 16 and older, the same day.
APhA’s Webinar Series addressing the COVID-19 Crisis: An Open Forum Webinar Series for Pharmacists on December 10, 2020, discussed breaking information about COVID-19 vaccines, including the latest in the development, approval, allocation, and distribution, as well as vaccine hesitancy. This is part of weekly webinars conducted every Thursday. Each open forum webinar is moderated by APhA President Michael Hogue. Here’s the link to the slides from the December 10th Webinar ASHP has upcoming webinars discussing the Pfizer-BioNTec COVID-19 vaccine EUA on 12/16/2020, a conversation with the Pfizer team regarding the vaccine on 12/17/2020 and a description supply chain management at five health systems on 12/21/2020. Several podcasts are also available, including a recent one on COVID-19 vaccine administration, allocation and uptake. Several resources are also available on ASHP’s COVID-19 vaccine page. Prescribe Right’s COVID-19 resource page, https://www.prescriberight.com/covid19.html contains links to the following content:
In addition, we have added these new resources COVID-19 Vaccine Information for Healthcare Providers (HCP) CDC COVID-19 Vaccination page The Advisory Committee on Immunization Practices’ (ACIP) Interim Recommendation for Allocating Initial Supplies of COVID-19 Vaccine: United States, 2020 ACIP Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine: United States, December 2020 Interim Clinical Considerations for Use of Pfizer-BioNTech COVID-19 Vaccine: Web page where the CDC will provide recommendations for special populations Training and Education materials for healthcare professionals preparing for COVID-19 vaccination: including Vaccine Storage and Handling Toolkit; COVID-19 Vaccine Training Module for Healthcare Professionals; and COVID-19 Vaccination Training Programs and Reference Materials for Healthcare Professionals. Post Vaccine Considerations for Healthcare Personnel: The CDC recommends scheduling vaccinations, so HCPs have 1-2 days off after vaccination, to help distinguish adverse effects from COVID-19 or influenza symptoms. CDC Guidance for Outpatient Pharmacies Information Systems Support COVID-19 Vaccination Reporting Data Systems: COVID-19 Vaccine IT Overview: Vaccine Allocation, Distribution, Administration, Data, and Reporting: COVID-19 Reporting Systems - Technical Standards & Reporting Data to CDC Vaccine Adverse Event Reporting System (VAERS) Patient Education COVID-19 Vaccination Communication Toolkit Talking to Patients about COVID-19 Vaccines Answering Patients’ Questions Making a Strong Recommendation for COVID-19 Vaccination COVID-19 Vaccines
An FDA review of clinical data for Pfizer and BioNTech’s COVID-19 vaccine found evidence supported 95% efficacy and no major safety concerns. On 12/10.2020, the FDA’s Vaccines and Related Biological Products Advisory Committee voted 17 to 4, with one abstention to recommend an emergency use authorization for BNT162b2 as prophylaxis for COVID-19 infections for patients 16 years and older. Pfizer and BioNTech will monitor for anaphylactic reactions as part of their pharmacovigilance plan after two patients in the U.K. developed reactions after receiving the vaccine. In the Pfizer funded, 43,0448 patient, Phase II/III trial (NCT04368728) BNT162b2 was administered as two 30 mcg immunizations given 21-days apart. BNT162b2 efficacy was found to be 95% (8 cases of COVID-19 vs 162 cases), 28 days after the first dose and 7 days after the second dose. Protection for COVID-19, began around 12 days after the first dose, with 52% efficacy between the first and second doses. Efficacy was consistent across age, gender, race and ethnicity demographics. The most common ADR were mild-to-moderate pain at the injection site, fatigue, and headache. There were few serious ADR and the incidence was similar to placebo. After the second dose, fever developed in 16% of younger patients and 11% of older patients. Pfizer and BioNtech will have 50 million vaccine doses available in 2020 and up to 1.3 billion doses in 2021. BioNTech announced that the COVID-19 vaccine it is developing with Pfizer, BNT162b2, can be stored for up to five-days at 2 to 8 C. The shipping container will keep the vaccine viable for up to ten days if stored at 15 to 25 C without opening and up to 15 days if opened and then re-iced with dry ice. The vaccine is stable for up to six months at -70 C. J&J and Operation Warp Speed are capping the ENSEMBLE trial at 40,000 patients due to a surge in COVID-19 cases that will allow accumulation of at least 154 cases of severe or moderate COVID-19 infection more quickly. The trial was estimated to be fully enrolled at the new participant total in the first week of December. An interim analysis of data from 11,636 patients participating in four trials (NCT04324606, (NCT04400838, NCT04444674, ISRCTN89951424 ) evaluating AstraZeneca’s COVID-19 vaccine (AZD1222 or ChAdOx1 nCoV-19) found the average efficacy for two dosing regimens of the vaccine to be 70% in preventing COVID-19. Giving a half dose as the first immunization and a full dose four weeks later resulted in 90% efficacy (n=2,741), while giving a full dose at both immunizations resulted in 62% efficacy (n=8,895). No safety issues were found. The vaccine can be stored, transported and handled at 2-8 degrees Celsius for at least six months. Sanofi and GSK announced a delay in their COVID-19 vaccine development program when an interim analysis of a 441 patient, Phase I/II trial (NCT04537208) found the vaccine to elicit antibodies comparable to convalescent plasma in patients 18 to 49, but the response in older patients was insufficient. Sanofi and GSK plan to initiate a Phase IIb trial in February 2021 to test a vaccine formulation with a higher antigen content. The Sanofi and GSK vaccine will be compared to a vaccine that has received an EUA. If the trial is successful, a Phase III is projected to be initiated in 2Q21. Clover announced that in a 150 patient, Phase I Australian trial (NCT04405908), Clover’s protein-based COVID-19 vaccine candidate combined with GSK’s vaccine adjuvant, ASO3 induced antibodies in all participants, while the vaccine adjuvanted with Dynavax’s vaccine adjuvant, CpG 1018 induced antibodies in 100% of younger and middle aged adults, but in 88% (7/8) of elderly patients. Clover plans a Phase IIb/III to evaluate the safety and efficacy of SCB-2019 in combination with GSK’s vaccine adjuvant, ASO3, by the end of 2020 and a Phase IIb/III to evaluate the safety and efficacy of SCB-2019 in combination with Dynavax’s vaccine adjuvant, CpG 1018, in the first half of 2021. CpG 1018 is used in Dynavax’s HEPLISAV-B (hepatitis-B) vaccine. COVID-19 Antibodies NIH did not find enough evidence to recommend for or against use of casirivimab plus imdevimab for the treatment of outpatients with mild to moderate COVID-19. Due to the limited supply, use of the drug should be restricted to patients at the highest risk to progress to severe COVID-19. Hospitalized patients should not receive bamlanivimab outside of a clinical trial. COVID-19 Vaccines
The British Medicines and Healthcare products Regulatory Agency (MHRA) approved the COVID-19 vaccine from Pfizer and BioNTech on 12/2/2020. The U.K. signed an agreement with Pfizer and BioNTech for 40 million doses of the vaccine. The vaccine will start to be distributed immediately with delivery to be completed in 2021 as vaccine supplies become available. The FDA’s Advisory Committee on Immunization Practices recommended that health care providers and long-term care residents be the first to be immunized for COVID-19. Health care providers includes those who work in hospitals, outpatient clinics, long-term care facilities, home health, public health, emergency medical services and pharmacies. COVID-19 Antivirals Interim results from the WHO sponsored, 11,330 patient, Phase II/III SOLIDARITY trial (NCT04315948), did not find an improvement in hospitalized COVID-19 patients treated with remdesivir, hydroxychloroquine, lopinavir or interferon compared to no drug in mortality, initiation of ventilation or duration of hospital stay. But some analysts did not agree with the study’s findings. A physician reviewer speculated that remdesivir may be more effective when given early in the infection to patients at high risk for progression. An editorialist highlighted the benefit of remdesivir“to change the course of hospitalization in some patients”. A second editorialist pointed out that SOLIDARITY was not designed to measure time to recovery or clinical improvement. COVID-19 Anti-inflammatories Remestemcel-L is a Mesenchymal Precursor Cell (Stem cell therapy) being developed by Mesoblast for the treatment of Acute Graft Versus Host Disease following allogeneic bone marrow transplantation. Remestemcel-L decreases pro-inflammatory cytokines, increases anti-inflammatory cytokines, and increases recruitment of naturally occurring anti- inflammatory cells to involved tissues. Due to these properties, Mesoblast is evaluating remestemcel-L to reduce cytokine storm in acute respiratory distress syndrome (ARDS) due to COVID-19 infection.
COVID-19 Vaccines
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet on Dec. 10, 2020 to review a request for an emergency use authorization (EUA) Pfizer’s and BioNTech’s COVID-19 vaccine. The FDA plans to do a live broadcast of the meeting. Moderna and NIAID initiated an NIAID funded, 30,000 patient, Phase III, COVE trial (NCT04470427) for COVID-19 vaccine candidate mRNA-1273 on July 27. The vaccine is administered as two 100 mcg immunizations given 28 days apart. Moderna announced final results from the COVE trial on 11/30/2020. The efficacy of mRNA-1273 was 94.1% based on 196 cases of COVID-19 that developed in the study population. The study population included 7,000 patients over the age of 65 and 5,000 under 65 at increased risk for severe COVID-19 due to co-morbidities. The study population also included 37% with diverse backgrounds, including 6,000 participants who identify as Hispanic or LatinX, and 3,000 who identify as Black or African American. The most common adverse effects were injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site. There was an increase in frequency and severity of adverse effects after the second immunization. Moderna submitted a request for an Emergency Use Authorization (EUA) from the FDA and EMA on 11/30/2020. When approved, Moderna will have 20 million vaccine doses available in 2020 and up to 1 billion doses in 2021. Moderna announced that mRNA-1273 is stable for 30 days at 2 to 8 C and for six-months at -20 C. This will make the vaccine easier to ship and use in pharmacies, clinics and small hospitals. Novavax plans to enroll 30,000 patients in a Phase III, Operation Warp Speed sponsored trial, in the U.S. and Mexico (NCT04611802). Due to difficulties in scaling up vaccine manufacturing, the initiation of the trial has been delayed a second time and is expected to begin at the end of December. Novavax initiated a 15,000 patient, Phase III trial to evaluate two doses of NVX-CoV2373 given 21-days apart for the prevention of COVID-19 in the United Kingdom (NCT04583995). At least 25% of trial participants will be 65 or older. Novavax completed enrollment in November 2020 and expects the first interim data to be reported in 1Q21. Novavax is evaluating two doses of NVX-CoV2373 given 21-days apart for the prevention of COVID-19 in South Africa in a 4,422 patient, Phase IIb trial (NCT04533399). The trial includes 245 medically stable, HIV-positive participants. AstraZeneca is designing a new trial to evaluate the efficacy of the half-strength initial dose/full strength second dose regimen that demonstrated 90% efficacy in a small subpopulation in a 22,690, Phase III trial. Gamaleya is evaluating Gam-COVID-Vac in the prevention of COVID-19 in the 40,000 patient Phase III (RESIST) trial (NCT04530396). Two doses of Gam-COVID-Vac will be given 21 days apart in the trial. The Russian National Research Center for Epidemiology and Microbiology announced results from a second interim analysis of the Sputnik V vaccine, where efficacy was estimated to be 91.4%, 28 days after the first dose and seven days after the second dose, based on the distribution of 39 cases of COVID-19 among 18,794 patients. (Note: Pfizer based their 95% efficacy on 170 cases distributed among 41,135 patients and Moderna reported 94.1% efficacy after 196 cases of COVID-19 occurred in over 30,000 patients). The Russian sovereign wealth fund announced the COVID-19 vaccine, Sputnik V, will be available internationally beginning in January 2021 as a two-dose regimen priced less than $20. COVID-19 Antibodies In a 30-day, 333 patient trial (NCT04383535), there was no difference in 30-day clinical status between treatment with convalescent plasma and placebo in Argentinian hospitalized patients with COVID-19. Most patients in the trial also received a glucocorticoid. |
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