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First study results for anti-SARS-CoV-2 antibody LY-CoV555

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On September 16, 2020, Eli Lilly and Company announced proof of concept data from an interim analysis of the Phase 2 BLAZE-1 clinical trial (NCT04427501) of LY-CoV555 (also known as LY3819253), an anti-SARS-CoV-2 IgG1 antibody. The randomized, double-blind, placebo-controlled study included 4 arms (placebo, 700 mg, 2800 mg, and 7000 mg administered intravenously (IV)), and enrolled mild-to-moderate recently diagnosed COVID-19 patients. Treatment is provided in an outpatient setting. The study was initiated on June 17, 2020 and has an estimated primary completion date of September 20, 2020.

  • The prespecified primary endpoint, change from baseline in viral load at day 11, was met at the 2800 mg dose level, but not the others. Additional analyses of viral data demonstrated that LY-CoV555 improved viral clearance at an earlier time point (day 3) and reduced the proportion of patients with persistently high viral load at later time points. Most patients, including those receiving placebo, demonstrated near complete viral clearance by day 11.
  • Analysis of pooled data from all dose groups indicated the rate of hospitalizations and ER visits was 1.7% (5/302) for LY-CoV555 vs. 6% (9/150) for placebo. Across all treatment groups (including placebo), no patients progressed to mechanical ventilation or died.
  • Viral RNA sequencing revealed putative LY-CoV555-resistance variants in placebo and all treatment arms. The rate of resistance variants was numerically higher in treated patients (8 percent) versus placebo (6 percent).
  • LY-CoV555 was well-tolerated, with no drug-related serious adverse events reported. Treatment emergent adverse events were similar across all dose groups and comparable to placebo.

Details for the BLAZE-1 study were updated on August 21, 2020 to include an experimental treatment arm comprising LY3819253 + LY3832479 (also known as LY-CoV016) administered IV.  LY-CoV016 binds a different epitope in the SARS-CoV-2 spike region compared to LY-CoV555. Across all treatment arms, the trial will enroll an estimated 800 participants.

Summary data for all anti-SARS-CoV-2 antibodies in clinical studies can be found here.

FDA issues Emergency Use Authorization for COVID-19 convalescent plasma

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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

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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

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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.

Antibody Engineering & Therapeutics Europe Poster Competition Winners Announced!

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Congratulations to our winners!

To recognize the research activities of promising student and postdoctoral attendees of Antibody Engineering & Therapeutics Europe, The Antibody Society sponsors a competition for members who submit posters for display at the meeting. Our judges select the best work based on originality, relevance and perceived impact on the field of antibody research and development.

This year, our judges selected one student and one postdoc winners who receive: 1) complimentary registration to all conference sessions; 2) an opportunity to give a short oral presentation of their work in one of the conference sessions; and 3) a lovely crystal award.

The winners of the contest are:

Ms. Monica Fernandez-Quintero (University of Innsbruck)
Poster title: Antibodies exhibit multiple paratope states that can differ in VH-VL domain orientations

Dr. Christian Fercher (University of Queensland)
Poster title: Development of Reagentless Fluorescence Immunosensors for Continuous Analyte Monitoring

Please join us for the virtual Antibody Engineering & Therapeutics Europe conference on August 24-27, 2020.

Society members receive a 15% discount on the registration fee. Contact us at membership@antibodysociety.org for the code.