| On February 11, 2022, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for bebtelovimab for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms, which is about 88 pounds) 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, and for whom alternative COVID-19 treatment options approved or authorized by the FDA are not accessible or clinically appropriate. Bebtelovimab is not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19. Treatment with bebtelovimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bebtelovimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. The dosage of bebtelovimab for emergency use in adults (18 years and older) and pediatric patients (≥12 years of age and weighing at least 40 kg) is bebtelovimab 175 mg administered as a single intravenous injection over at least 30 seconds. Administer bebtelovimab as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset. Mechanism of Action (MOA) and Pharmacokinetics (PK) MOA: Bebtelovimab is a recombinant neutralizing human IgG1κ monoclonal antibody (mAb) to the spike protein of SARS-CoV-2 and is unmodified in the Fc region. Bebtelovimab binds the spike protein and blocks spike protein attachment to the human ACE2 receptor. General PK: A summary of PK parameters of bebtelovimab following administration of a single dose of 175 mg bebtelovimab is presented below as geometric mean (%CV). | PK Parameter | Bebtelovimab (175 mg) (N = 573) | | Systemic Exposure | | Cmax, mcg/mL | 59.8 (30.1) | | Cday 29, mcg/mL | 4.35 (69.8) | | AUCinf, mcg day/mL | 522 (39.3) | | Distribution | | Vss (L) | 4.61 (25.3) | | Elimination | | Elimination Half-Life (day) | 11.5 (25) | | Clearance (L/day) | 0.335 (39.3) | Use in Specific Populations The PK profile of bebtelovimab was not affected by age, sex, race, or baseline viral load based on a population PK analysis. Body weight had no clinically relevant effect on the PK of bebtelovimab in adults with COVID-19 over the body weight range of 45 kg to 194 kg. Renal impairment is not expected to impact the PK of bebtelovimab, since mAbs with molecular weight >69 kDa are known not to undergo renal elimination. Similarly, dialysis is not expected to impact the PK of bebtelovimab. Based on population PK analysis, there is no significant difference in PK of bebtelovimab in patients with mild hepatic impairment compared to patients with normal hepatic function. Bebtelovimab has not been studied in patients with moderate or severe hepatic impairment. Pediatric Population Bebtelovimab is not authorized for use in pediatric individuals under 12 years of age or weighing less than 40 kg. The safety and effectiveness of bebtelovimab have not been assessed in pediatric patients. The recommended dosing regimen in patients 12 years to less than 18 years of age, weighing at least 40 kg, is expected to result in comparable serum exposures of bebtelovimab as those observed in adults. Drug Interaction Studies Bebtelovimab is not renally excreted or metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely. Efficacy and Safety The issuance of an EUA is different than an FDA approval. In determining whether to issue an EUA, the FDA evaluates the totality of available scientific evidence and carefully balances any known or potential risks with any known or potential benefits of the product. Based on the FDA's review of the totality of the scientific evidence available, the agency has determined that it is reasonable to believe that bebtelovimab may be effective in treating certain patients with mild or moderate COVID-19. When used to treat COVID‑19 for the authorized population, the known and potential benefits of these antibodies outweigh the known and potential risks. There are no adequate, approved and available alternative treatments to bebtelovimab. Efficacy The EUA for bebtelovimab is supported by clinical and nonclinical data. The clinical data are from a phase 2, randomized, single-dose clinical trial evaluating the efficacy of bebtelovimab alone and bebtelovimab combined with other monoclonal antibodies for treating mild to moderate COVID-19. The placebo-controlled portion of the trial enrolled 380 low-risk patients (i.e., patients without risk factors for progression to severe COVID-19 illness). Patients in this part of the trial were randomized to receive a single infusion of bebtelovimab alone, bebtelovimab with other monoclonal antibodies or a placebo. Treatment with bebtelovimab resulted in a reduction in time to sustained symptom resolution compared to placebo. Reduction in viral load relative to placebo was also seen on Day 5 after treatment. In another part of the trial involving mostly high-risk individuals (i.e. patients with risk factors for progression to severe COVID-19 illness), 150 patients were randomized to receive a single infusion of bebtelovimab alone or a single infusion of bebtelovimab with other monoclonal antibodies. An additional 176 high-risk patients received bebtelovimab with other monoclonal antibodies in an open-label treatment arm. The rates of COVID-19 related hospitalization and death through Day 29 seen in those who received bebtelovimab alone or with other monoclonal antibodies were generally lower than the placebo rate reported in prior trials of other monoclonal antibodies in high-risk patients. Conclusions are limited as these data are from different trials that were conducted when different viral variants were circulating and baseline risk factors varied. Safety Possible side effects of bebtelovimab include itching, rash, infusion-related reactions, nausea and vomiting. Serious and unexpected adverse events including hypersensitivity, anaphylaxis and infusion-related reactions have been observed with other SARS-CoV2 monoclonal antibodies and could occur with bebtelovimab. In addition, clinical worsening following administration of other SARS-CoV-2 monoclonal antibody treatment has been reported and therefore is possible with bebtelovimab. It is not known if these events were related to SARS-CoV-2 monoclonal antibody use or were due to progression of COVID-19. Additional Information The Fact Sheet for Health Care Providers provides essential information about using bebtelovimab in treating COVID-19 as authorized and is available at https://www.fda.gov/media/156152/download. A fact sheet for patients, parents, and caregivers is available at https://www.fda.gov/media/156153/download and contains information for understanding the potential risks and potential benefits of taking bebtelovimab, including side effects. The EUA authority allows FDA to help strengthen the nation's public health protections against chemical, biological, radiological, and nuclear threats by facilitating the availability and use of medical countermeasures needed during public health emergencies. For additional information on the EUA authority and EUAs for COVID-19, please visit https://go.usa.gov/xs8x4. The FDA is working with sponsors of all currently authorized therapeutics to assess the activity against any global SARS-CoV-2 variant(s) of interest and is committed to communicating with the public as we learn more. | 
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