The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

You are here: Home / Archives for Food and Drug Administration

Antibodies to Watch in a Pandemic

by

The extraordinary scale of the COVID-19 pandemic has elicited extraordinary responses world-wide, but the resulting disruptions have raised concerns about delays in approval of non-COVID-19 antibody therapeutics.

As part of the virtual Antibody Engineering & Therapeutics Europe conference, Dr. Janice Reichert, Executive Director of The Antibody Society,  provided an update on non-COVID-19 antibody therapeutics approved so far in 2020, and those that might be approved by the end of the year. She also discussed the biologics currently in development for COVID-19, which includes over 50 repurposed biologics and over 80 anti-SARS-CoV-2 biologics.

Broadcast date: Thursday August 27, 2020.

Updated presentation slides can be downloaded here.

Dataset of commercially sponsored biologic COVID-19 interventions can be downloaded here.

FDA issues Emergency Use Authorization for COVID-19 convalescent plasma

by

On August 23, 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for investigational COVID-19 convalescent plasma (CCP) for the treatment of COVID-19 in hospitalized patients. CCP is human plasma collected by FDA-registered blood establishments from individuals whose plasma contains anti SARS-CoV-2 antibodies, and who meet all donor eligibility requirements and are qualified. Titer levels of anti-SARS-CoV-2 antibodies are determined by the Ortho VITROS SARS-CoV-2 IgG test before units of CCP are released. Units found to have a signal-to-cutoff ratio of 12 or greater qualify as High Titer COVID-19 Convalescent Plasma.

Based on scientific evidence available, the FDA concluded CCP may be effective in treating COVID-19, and that the known and potential benefits of CCP outweigh the known and potential risks of the product. The EUA authorizes the distribution of COVID-19 convalescent plasma in the U.S. and its administration by health care providers, as appropriate, to treat suspected or laboratory-confirmed COVID-19 in hospitalized patients with COVID-19.

Data obtained from the ongoing National Convalescent Plasma Expanded Access Protocol (EAP) sponsored by the Mayo Clinic was included in FDA assessment. This uncontrolled, single-arm study was established in April 2020 to provide access to COVID-19 convalescent plasma in hospitalized subjects with severe or life-threatening COVID-19 or judged by the treating provider to be at high risk of progression to severe or life-threatening disease. As of August 13, 2020, over 90,000 patients have been enrolled. Data from the EAP posted online on August 12, 2020 reveals trends toward reduced mortality when patients receive CCP with higher antibody levels and at earlier time points. According to FDA’s decision memorandum:

  • In the subset of non-intubated patients, there was a 21% reduction in 7-day mortality (from 14% to 11%, p=0.03) in subjects transfused with high versus low titer CCP.
  • In the subgroup of patients less than 80 years of age who were not intubated and who were within 72 hours of diagnosis, a significant reduction in 7-day mortality from 11.3 to 6.3% (p = 0.0008) was observed when titers are binned to low versus high.
  • Survival trends observed at 7 days persisted over a longer time period, with significantly improved survival in non-intubated patients (p=0.032) and a larger benefit in the subset of patients not intubated at the time of treatment, less than 80 years of age, who were treated within 72 hours of diagnosis (p=0.0081)

However, there was no difference in 7-day survival in the overall population between subjects transfused with high versus low titer CCP, and there was no apparent association between neutralizing antibody titers and 7-day mortality in intubated subjects.

Information from the EUA and clinical studies of CCP may inform the development of other biologic COVID-19 interventions, such as recombinant anti-SARS-CoV-2 antibodies.  The Antibody Society is currently tracking 10 such antibodies in clinical studies or with clinical studies pending. We will report on the progress of these molecules and other COVID-19 interventions in the future.

Satralizumab-mwge (ENSPRYNG) granted FDA approval

by

On August 14, 2020, the US Food and Drug Administration approved satralizumab-mwge (ENSPRYNG) for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. NMOSD is a rare autoimmune disorder of the central nervous system that primarily damages the optic nerve(s) and spinal cord, causing blindness, muscle weakness and paralysis. ENSPRYNG was previously approved in Canada, Japan and Switzerland. Applications are under review with other regulatory agencies, including in the European Union and China.

ENSPRYNG is a recombinant humanized IgG2 antibody targeting interleukin-6 (IL-6) receptor. The efficacy of ENSPRYNG for the treatment of NMOSD in adult patients was established in two studies. SAkuraStar (NCT02073279) was a randomized (2:1), placebo-controlled trial in 95 patients without concurrent immunosuppressive therapy (IST) in which 64 patients were anti-AQP4 antibody positive and 31 patients were anti-AQP4 antibody negative. SAkuraSky (NCT02028884) was a randomized (1:1), placebo-controlled trial in 76 adult patients with concurrent IST. Of these, 52 adult patients were anti-AQP4 antibody positive and 24 adult patients were anti-AQP4 antibody negative. In the SAkuraStar monotherapy study’s AQP4 antibody positive subgroup, 76.5% of Enspryng-treated patients were relapse-free at 96 weeks, compared to 41.1% with placebo. In the SAkuraSky study, which evaluated Enspryng when used concurrently with baseline IST, 91.1% of Enspryng-treated AQP4 antibody positive subgroup patients were relapse-free at 96 weeks, compared to 56.8% with placebo. Based on results of the clinical studies, the recommended loading dosage of ENSPRYNG for the first three administrations is 120 mg by subcutaneous injection at Weeks 0, 2, and 4, followed by a maintenance dosage of 120 mg every 4 weeks.

Satralizumab-mwge is the 8th antibody therapeutic to be granted a first approval in the US or EU in 2020.

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format. Information about other antibody therapeutics that may enter regulatory review in 2020 can be found in ‘Antibodies to watch in 2020’.

Emergency Use Authorization requested for leronlimab

by

On August 12, 2020, Cytodyn requested that the Food and Drug Administration grant an Emergency Use Authorization for leronlimab for mild to moderate COVID-19 based on data from the Phase 2 CD10 study (NCT04343651). In this study, patients were randomized to receive weekly doses of 700 mg leronlimab or placebo, both of which were administered via subcutaneous injection. Top-level results of the study showed that, in patients with Total Clinical Symptom Scores of ≥ 4 at baseline (higher scores equate to poorer health state), at Day 3, more subjects treated with leronlimab reported improvement in total clinical symptom score compared to the placebo group (90% on leronlimab arm vs. 71% on placebo). The EUA request was disclosed in an investment community conference call that will be available until September 12, 2020.

  • Leronlimab is a humanized IgG4 antibody targeting C-C chemokine receptor type 5.

FDA grants first approval to belantamab mafodotin-blmf

by

On August 5, 2020, the U.S. Food and Drug Administration (FDA) approved belantamab mafodotin-blmf (BLENREP) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. BLENREP was granted an accelerated approval for this indication based on response rate. Further adequate and well-controlled studies/clinical trials must be done to verify and describe clinical benefit.

Belantamab mafodotin-blmf is an antibody-drug conjugate (ADC) composed of a humanized IgG1 monoclonal antibody and the cytotoxic agent maleimidocaproyl monomethyl auristatin F. The ADC binds to B-cell maturation antigen found on myeloma cell surfaces and is internalized. In the cell, the cytotoxic agent is released and kills the cells.

Belantamab mafodotin-blmf was evaluated in the Phase 2 DREAMM-2 (NCT03525678), an open-label, multicenter trial. Efficacy was based on overall response rate (ORR) and response duration. In patients receiving the recommended dose of 2.5 mg/kg, the ORR was 31% (97.5% CI: 21%, 43%) 73% of responders had response durations ≥6 months. Detailed results of the study were published in The Lancet Oncology in February 2020.

On July 24, 2020, the European Medicines Agency’s (EMA) human medicines committee recommended granting a conditional marketing authorization in the European Union for Blenrep (belantamab mafodotin) to treat adult patients with relapsed and refractory multiple myeloma who no longer respond to treatment with an immunomodulatory agent, a proteasome inhibitor and a CD-38 monoclonal antibody. Blenrep was accepted in EMA’s PRIME scheme, and it was designated as an orphan medicinal product. EMA recommended a conditional marketing authorization, and this opinion was sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Antibodies to watch

Belantamab mafodotin-blmf is the 7th antibody therapeutic to be granted a first approval in the US or EU in 2020. The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format. Information about antibody therapeutics approved outside the US or EU can be found in the table notes.

Information about other antibody therapeutics that may enter regulatory review in 2020 can be found in ‘Antibodies to watch in 2020’.

Like this post but not a member? Please join!