The FDA expanded the emergency use authorization for remdesivir to include treatment of any hospitalized adult or pediatric patients with suspected or laboratory-confirmed COVID-19, irrespective of their severity of disease. The expansion was based on evidence demonstrating a benefit in patients with mild-to-moderate disease.
AstraZeneca initiated a 48 patient, Phase I trial in August, to evaluate its two monoclonal antibody combination, AZD7442, as a treatment for hospitalized COVID-19 patients (NCT04507256). The trial is being sponsored by DARPA and BARDA.
Vir and GSK initiated the Phase II/III, COMET-ICE trial in August to evaluate VIR-7831 as a treatment for COVID-19. The Phase II part of the trial will evaluate the safety and tolerability of VIR-7831 in 20 non-hospitalized, COVID-19 patients. The 29-day, 1,300 patient, Phase III part of the trial will evaluate whether VIR-783 prevents mild or moderate COVID-19 patients from worsening as indicated by an increase in hospitalizations or death.
The FDA’s Vaccine Advisory Committee will meet on October 22 for a general discussion on the development, authorization and/or licensure of vaccines to prevent COVID-19. No specific vaccine will be discussed at the meeting. The FDA plans to offer a free live broadcast of the meeting and make background material and slides available before the meeting.
CanSino has canceled a Phase II/III trial in Canada, after the Chinese government refused to allow the company to ship the vaccine to Canada for the trial. The CanSino COVID-19 vaccine, Ad5-nCoV, is based on technology developed by Canadian firm NRC.
In an 11-day, 584 patient, Phase III, open-label trial (NCT04292730), patients treated with a 5-day course of remdesivir were more likely to have at least a 2-point improvement on a seven-point scale that runs from death to not hospitalized compared to placebo (70% vs 61%) in hospitalized patients with moderate COVID-19. A 10-day course of remdesivir did not differ from placebo (65% vs 61%), although most patients did not receive a full 10-days of treatment. Patients in the standard of care group were more likely to receive lopinavir-ritonavir, corticosteroids, hydroxychloroquine/chloroquine, azithromycin or tocilizumab.
The FDA issued an emergency use authorization (EUA) for convalescent plasma, on 8/23/2020, for the treatment of hospitalized patients with COVID-19. The EUA was granted for any convalescent plasma product “collected by FDA registered blood establishments from individuals whose plasma contains anti-SARS-CoV-2 antibodies, and who meet all donor eligibility requirements." Fact sheets have been created for health care providers and patients. The documents include dosing instructions and potential adverse effects, such as allergic reactions, transfusion-associated circulatory overload, and transfusion associated lung injury, as well as the potential for transfusion-transmitted infections.
In an unpublished, 35,322 patient, open-label trial, the seven-day mortality was 8.7% in patients treated with convalescent plasma within 3 days of diagnosis, and 11.9% if transfused four or more days later in patients hospitalized with COVID-19. Lower mortality was also seen with convalescent plasma that had higher antibody levels. Data from the trial was collected from patients treated through a convalescent plasma expanded access program for COVID-19 (NCT04338360).
Sinopharm has priced its COVID-19 vaccine at $145 for two doses.
Regeneron has signed an agreement with Roche to increase manufacturing capacity and distribution of REGN-COV2, Regeneron’s mixture of two monoclonal COVID-19 antibodies. Roche will triple the manufacturing capacity for REGN-COV2 and handle distribution outside the U.S.
Aviptadil (RLF-100) is a synthetic human Vasoactive Intestinal Polypeptide. Aviptadil blocks the replication of the SARS coronavirus in human lung cells and monocytes. The drug has been in clinical trials since 2001 and was unsuccessfully evaluated for Acute Respiratory Distress Syndrome and Pulmonary Arterial Hypertension.
Tradipitant is a neurokinin-1 receptor (NK-1R) antagonist being developed by Vanda Pharmaceuticals for the treatment of diabetic gastroparesis, motion sickness, and atopic dermatitis. By inhibiting NK-1R, tradipitant is thought to decrease inflammatory lung injury associated with severe or critical COVID-19 pneumonia.
Experts have estimated that initial supplies of a COVID-19 vaccine will only allow immunization of health care employees. A larger supply that will allow mass immunization may not be available until spring or summer 2021.
Russia has approved a COVID-19 vaccine after limited Phase I testing. The vaccine has been named Sputnik V. No clinical data has been made available. Two small clinical trials with a total of 76 patients are claimed to have been conducted which resulted in antibodies being produced. A larger trial is now being planned.
HHS and the BARDA awarded Moderna $1.5 billion for the first 100 million doses ($15 per dose) of its experimental COVID-19 vaccine, mRNA-1273, as part of operation Warp Speed. The U.S. has an option to acquire additional 400 million doses. Should the vaccine be approved, the Federal supply will be provided at no charge, but health care providers can charge for administration. The $1.5 billion is in addition to the $955 million provided to Moderna for vaccine development and manufacturing scale-up.
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. Novavax feels it will have the capacity to produce two billion doses of the NVX-CoV2373 annually beginning in 2021.
AstraZeneca has agreements with Brazil, Argentina and Mexico to manufacturer AZD1222 to supply patients in Central and South America.
CanSino plans to initiate a 5,000 patient, Phase III trial in Saudi Arabia.
In a 96 patient, Phase I, dose ranging trial, (ChiCTR2000031809) patients received three immunization of adjuvant alone or Sinopharm’s COVID-19 vaccine at low, middle or high strengths (2.5 mcg, 5 mcg or 10 mcg). The second immunization was given at 28 days and the third vaccine was given on day 56. All vaccine doses elicited neutralizing antibodies 14 days after the third dose. In a 224 patient, Phase II, trial, (ChiCTR2000031809) patients received two immunization of adjuvant alone or 5 mcg of Sinopharm’s COVID-19 vaccine. The second immunization was given at 14 or 21 days. The vaccine elicited neutralizing antibodies 14 days after the third dose at levels greater than adjuvant alone. The researchers did not compare levels of antibodies to those seen in recovered patients. The researcher claim the levels of neutralizing antibodies in the ChiCTR2000031809 Phase I and II trials were similar to those seen in other COVID-19 vaccine trials. However, different patient populations and different methods to measure antibodies were used, so caution is needed in comparing the levels of neutralizing antibodies.
Vir plans to initiate a Phase II/III trial in August to evaluate VIR-7831 as a treatment for COVID-19.
Interim results from 60 patients enrolled in a Russian COVID-19 trial, suggested that on day 5, treatment with favipiravir cleared SARS-CoV-2 in 62.5% of patients compared to 30% of patients on standard of care. There was no difference in clearance by day 10 (92.5% vs 80%). Most patients in the standard of care group received hydroxychloroquine, chloroquine or lopinavir/ritonavir. Standard of care treatment was not described, but included antibiotics, anticoagulants and/or immunosuppressants, as well as symptomatic treatment. Body temperature normalized 2 days earlier with favipiravir (2 days vs 4 days), but there was no difference in chest CT scan.
Sanofi and GlaxoSmithKline received a $2.1 billion grant from Operation Warp Speed to fund clinical trials, scale up manufacturing, and deliver 100 million doses of their COVID-19 vaccine to the U.S. The deal also includes an option for an additional 500 million doses.
The Departments of Defense and Health and Human Services, as part of Operation Warp Speed, have awarded Johnson & Johnson $1 billion for the first 100 million doses ($10 per dose) of its experimental COVID-19 vaccine. The supply will be used for clinical trials or provided, at no charge, through a U.S. vaccination program. The U.S. government also has an option for an additional 200 million doses.
Moderna has signed some early vaccine supply deals, pricing their COVID-19 vaccine at $32 to $37 per dose or $64 to $74 per two dose regimen. These early deals were for smaller supplies, so larger orders could have a lower cost per dose, but Moderna has not specified what the price might be. A price for a U.S. government purchase has not yet been determined.
Novavax announced that in a 131 patient, Phase I trial (NCT04368988), the antibody level increased with all doses of its NVX-CoV2373 COVID-19 vaccine with or without the Matrix-M adjuvant. Either formulation of the vaccine with adjuvant induced neutralizing antibody levels greater than what is seen in recovered COVID-19 patients. The trial was sponsored by the Coalition for Epidemic Preparedness Innovations and performed in Australia. Novavax is evaluating NVX-CoV2373 in a 1,500 patient, Phase II trial in the U.S. and Australia.
Zydus is developing a DNA vaccine (ZyCoV-D)
Lilly initiated the NIAID sponsored, 2,400 patient, Phase III, BLAZE-2 trial to assess the prophylactic potential of LY-CoV555 in long-term care residents. BLAZE-2 will assess whether a single dose of LY-CoV555 reduces the rate of COVID-19 through 4 weeks and COVID-19 complications through 8 weeks.
The Pharmaceutical Pipeline Tracker COVID-19 Antibody page now includes new clinical trials for two products (BRII-196 and BRII-198) and two new monoclonal products that have also entered clinical testing:
Sinocelltech is evaluating SCTA01 as a potential treatment for COVID-19 infection.
BARDA ceased funding IL-6 inhibitor trials evaluating tocilizumab and sarilumab as treatments for severe COVID-19 in August 2020. Tocilizumaband sarilumab have each failed to demonstrate improvements in clinical trials.
In a 28-day, 56-patient, observational study, 28 patients that received sarilumab were compared to 28 that did not receive the drug. Treatment with sarilumab did not improve clinical status or mortality in patients with severe COVID-19 pneumonia and systemic hyperinflammation. The study suggested that sarilumab may speed recovery in patients with minor lung consolidation at baseline. This study used a subset of patients from the Italian, 1,000 patient, COVID-BioB observational study (NCT04318366).
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