the official website of the antibody society
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Please nominate suitable candidates by Oct 31st using this survey.
On October 14, 2020, FDA approved the triple antibody cocktail of atoltivimab, maftivimab, and odesivimab-ebgn (Inmazeb) for the treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. Atoltivimab, maftivimab, and odesivimab are IgG1 antibodies that bind glycoprotein on the surface of Ebola virus, thereby blocking attachment and entry of the virus into cells. FDA granted the atoltivimab, maftivimab, and odesivimab cocktail Breakthrough Therapy and Orphan Drug designations for the approved indication. Inmazeb was developed by Regeneron.
The effects of Inmazeb were evaluated in adult and pediatric patients with confirmed infections that occurred during an Ebola virus outbreak in the Democratic Republic of the Congo in 2018 and 2019. In the Pamoja Tulinde Maisha (PALM) study (NCT03719586), a 4-arm trial evaluating investigational therapies for Ebola virus infection initiated in November 2018, 154 patients received Inmazeb as a single IV infusion of 50 mg of each monoclonal antibody. The primary efficacy endpoint was 28-day mortality. At this timepoint, 33% of those who received Inmazeb had died vs 51% of those who received a control. Inmazeb was also made available in an expanded access program, which included an additional 228 patients who received Inmazeb. The PALM study was sponsored by the US National Institute of Allergy and Infectious Diseases, with collaborators from Institut National de Recherche Biomédicale (Democratic Republic of Congo); the Alliance for International Medical Action (Senegal); International Medical Corps, Los Angeles (US); Epicentre, Médecins sans Frontières, (France); and the World Health Organization (Switzerland).
Inmazeb is the 9th 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.
On October 7, 2020, Eli Lilly and Company and Regeneron announced that they have submitted requests to the U.S. Food and Drug Administration (FDA) for emergency use authorizations (EUA) of their anti-SARS-CoV-2 monoclonal antibodies.
Lilly’s EUA request is for bamlanivimab (LY-CoV555) monotherapy in higher-risk patients who have been recently diagnosed with mild-to-moderate COVID-19. According to the company, up to 100,000 doses of 700 mg LY-CoV555 monotherapy may be available in October, and one million doses available in Q4 2020.
The combination of LY-CoV555 and LY-CoV016, which bind complementary regions of the SARS-CoV-2 spike protein, for the treatment of symptomatic COVID-19 in an outpatient setting is also being evaluated. Lilly anticipates submission of an EUA request for combination therapy in November, and may have data to support a biologics license application submission for combination therapy as early as Q2 2021.
Regeneron’s EUA request is for REGN-COV2, which is a combination of two anti-SARS-CoV-2 monoclonal antibodies (REGN10933 and REGN10987). Regeneron was granted a $450 million contract to manufacture and supply REGN-COV2 by the US government, which has committed to making the doses available to Americans for free. The agreement covers a fixed number of bulk lots that are intended to be completed in the fall of 2020, as well as fill/finish and storage activities. At the time of the EUA request, Regeneron had doses available for ~ 50,000 patients, and expects to have doses available for a total of 300,000 patients within several months.
The Antibody Society is tracking the progress of recombinant biologic COVID-19 interventions in preclinical and clinical studies. Summary data for all anti-SARS-CoV-2 antibodies in clinical studies can be found here.
The first biologics license applications (BLAs) for two antibody therapeutics, balstilimab (AGEN2034) and loncastuximab tesirine (ADCT-042), have recently been submitted to the US Food and Drug Administration, bringing the total number of antibody therapeutics undergoing a first review to 18 (see table here for details).
Balstilimab (AGEN2034) is a human IgG4k antibody directed against PD-1, a negative regulator of immune activation expressed by T cells. Numerous antibodies that target PD-1 or its ligand PD-L1 (e.g., pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab) are marketed as treatments for solid tumors as well as lymphoma. Agenus’ clinical studies of balstilimab have focused on its use, either as monotherapy or in combination with anti-CTLA4 zalifrelimab (AGEN1884), as a treatment for cervical cancer. FDA granted both balstilimab and the balstilimab/ zalifrelimab combination Fast Track designations for the treatment of cervical cancer. On September 18, 2020, Agenus Inc. announced that they had initiated a rolling BLA to FDA for balstilimab as monotherapy for the treatment of recurrent/metastatic cervical cancer. Agenus controls worldwide rights to balstilimab, except for certain South American rights, which are controlled by Recepta Biopharma, and Greater China rights, which are exclusively licensed to Betta Pharmaceuticals.
Data from a randomized, blinded, non-comparative, two-arm Phase 2 study (NCT03894215) supported the BLA submission. This study evaluated the efficacy and safety of balstilimab as monotherapy or in combination with zalifrelimab for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy for a maximum of 24 months, or until disease progression or unacceptable toxicity. The goal of the study is to evaluate the efficacy of each arm against its relevant historical controls. The primary outcome measure is the objective response rate (ORR) to balstilimab administered with placebo (Treatment Arm 1 – monotherapy), or with zalifrelimab (Treatment Arm 2 – combination therapy). Data from the study were presented at the 2020 European Society for Medical Oncology Virtual Congress. Of 160 patients included in the balstilimab monotherapy arm, the ORRs in PD-L1-positive patients and all patients were 19% and 14%, respectively. Of 143 patients included in the balstilimab/ zalifrelimab combination arm, the ORRs in PD-L1-positive patients and all patients were 27% and 22%, respectively.
Loncastuximab tesirine (ADCT-042) is an ADC composed of an anti-CD19 humanized IgG1k antibody conjugated via a linker to pyrrolobenzodiazepine (PBD)-dimer toxin that induces the killing of CD19-expressing malignant B cells. The FDA granted Orphan Drug designation to ADCT-402 for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. On September 21, 2020, ADC Therapeutics SA announced the submission of a BLA to FDA for loncastuximab tesirine for the treatment of patients with relapsed or refractory DLBCL.
The BLA submission was supported by data from the open-label, single-arm Phase 2 LOTIS 2 study (NCT03589469), which evaluated the safety and efficacy of loncastuximab tesirine for the treatment of patients with relapsed or refractory DLBCL following ≥2 lines of prior systemic therapy. A total of 145 patients received loncastuximab tesirine as an IV infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg for 2 cycles, then 75 μg/kg for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria. The primary outcome measure is the overall response rate (ORR). Positive initial data from LOTIS 2 were presented during the virtual 25th Annual Congress of the European Hematology Association. The ORR was 48.3% (70/145 patients), the complete response rate (CRR) was 24.1% (35/145 patients), and the median duration of response was 10.25 months. The toxicity profile was manageable and no new safety concerns were identified.
