COVID-19 Update #40 for 9/4/2020

COVID-19 Vaccines
 
Gamaleya Research Institute is developing Gam-COVID-Vac (Sputnik V), a non-replicating adenovirus type-5 (Ad5) viral vector DNA virus. Russia approved the COVID-19 vaccine after limited Phase I testing. 

• Gam-COVID-Vac is being developed as both a frozen and lyophilized form. The lyophilized vaccine does not require freezing, which may make it easier to distribute in developing nations.
• Two 38 patient, Phase I/II clinical trials (NCT04436471 and NCT04437875) demonstrated that antibodies were produced. Two doses of Gam-COVID-Vac were given 21 days apart in the Phase II 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.

 
AstraZeneca paused all clinical trials for its COVID-19 vaccine (AZD1222), on 9/6/2020, due an adverse event in one patient. The patient suffered neurological symptoms consistent with transverse myelitis. The UK Medicines Health Regulatory Authority investigated the occurrence as a potential safety problem and allowed the trial to continue on 9/12/2020. The FDA is still investigating the adverse event and had not allowed the trial to resume in the U.S. as of 9/15/2020.
 
Pfizer and BioNTech are evaluating BNT162b2 in a Pfizer funded, 44,000 patient, Phase II/III trial (NCT04368728) BNT162b2 will be administered as two 30 mcg immunizations given 21-days apart. The trial was expanded from its original 30,000 patients, in September 2020, to allow the vaccine to be tested in a larger more diverse population, including adolescents as young as 16 years of age and people with HIV, Hepatitis C, and Hepatitis B.
 
Novavax purchased Praha Vaccines and its Czech Republic vaccine factory. That plant has an annual capacity of one billion doses per year. Novavax signed an agreement with Fujifilm Diosynth Biotechnologies to manufacture its COVID-19 vaccine, NVX-CoV2373, in North Carolina and Texas. Novavax also signed contracts with AGC Biologics and PolyPeptide to help produce its Matrix-M adjuvant. In addition Novavax has an agreement with Serum Institute of India to manufacture the antigen component of NVX‑CoV2373. The company now has six antigen production sites and three adjuvant manufacturing sites. This gives Novavax the capacity to produce two billion doses of the NVX-CoV2373 annually beginning in 2021.
 
COVID-19 Treatment
 
Granulocyte colony-stimulating factor (G-CSF) was evaluated as a treatment for COVID-19 in a Chinese trial. G-CSF increases peripheral blood leukocyte and lymphocyte and was theorized to be beneficial in COVID-19 patients with lymphopenia. Filgrastim (Neupogen, Amgen) is a G-CSF. Lenograstim is a G-CSF developed by Chugai and available in some countries as Granocyte.

• In a 21-day. 200 patient, Chinese trial, treatment with G-CSF improved a 7-category disease severity score by at least 1 point in 12 days vs 13 days with usual care in patients with COVID-19 with lymphopenia but no comorbidities. A small number of patients used interferon (9%), lopinavir/ritonavir (15%) or arbidol (18%) before enrollment. 

 
COVID-19 Anti-Inflammatories
 
Lilly announced that in the 29-day, 1,034 patient, Phase III, ACTT 2 trial (NCT04401579), baricitinib added to remdesivir reduced the time to hospital discharge by one day compared to remdesivir alone in hospitalized patients with COVID-19. ACTT 2 is sponsored by NIAID.
 
COVID-19 Antibodies
 
The University of Oxford will evaluate the effect of REGN-COV2 added to standard-of-care on all-cause mortality at 28 days in a new 2,000 patient arm of the RECOVERY trial. The 11,500 patient RECOVERY trial (NCT04381936) has several arms testing lopinavir-ritonavir, dexamethasone, hydroxychloroquine, azithromycin, tocilizumab and convalescent plasma.