Antibody therapeutic Archives - The Antibody Society

FDA approves Veopoz (pozelimab-bbfg) for CHAPLE disease

August 18, 2023 by Janice Reichert

On August 18, 2023, the US Food and Drug Administration (FDA) approved Veopoz (pozelimab-bbfg) injection for the treatment of adult and pediatric patients 1 year of age and older with CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease. Pozelimab (REGN3918) is a human IgG4k antibody targeting complement component 5 (C5) developed by Regeneron. Veopoz received fast track, orphan drug, and rare pediatric disease designations.

Veopoz is the first FDA-approved treatment for CHAPLE disease. An initial dose of 30 m/kg Veopoz is administered intravenously (IV), followed by weekly injections of 10 m/kg given subcutaneously by a health care provider. See the prescribing information for details

The efficacy and safety study of pozelimab in patients with CHAPLE were evaluated in an open-label, single arm Phase 2/3 study (NCT04209634). The study included 10 patients from 3 to 19 years of age with a clinical diagnosis of CD55-deficient PLE disease who received a single loading IV dose on Day 1, then fixed SC doses based on body weight every week over the treatment period. The primary outcome measure of the study was the proportion of patients with active disease at baseline achieving both normalization of serum albumin and clinical outcome improvement. All 10 patients achieved a serum albumin concentration of at least 3.5 g/dL by week 12, which was maintained through at least 72 weeks. All 10 patients also demonstrated a reduction in the number of hospitalizations and number of albumin transfusions over the first 48 weeks of treatment as compared to the 48 weeks prior to treatment.

Interested in data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

Elranatamab-bcmm (Elrexfio) approved for multiple myeloma

August 15, 2023 by Janice Reichert

On August 14, 2023, the Food and Drug Administration (FDA) granted accelerated approval to elranatamab-bcmm (Elrexfio, Pfizer, Inc.) for adults with relapsed or refractory multiple myeloma (r/r MM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The biologics license application (BLA) for elranatamab was granted priority review, breakthrough designation and orphan drug designation by FDA.

Elranatamab (PF-06863135) is a humanized IgG2a T cell-engaging bispecific antibody designed to target BCMA, which is highly expressed on tumor cells, and CD3 found on the T cell surface. Developed by Pfizer, elranatamab is formulated for subcutaneous, rather than intravenous, administration. The recommended elranatamab-bcmm dosages include the following: “step-up dose 1” of 12 mg on Day 1, “step-up dose 2” of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly, thereafter, through week 24.

The prescribing information for elranatamab-bcmm includes a Boxed Warning for life threatening or fatal cytokine release syndrome and neurologic toxicity. Elrexfio is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the ELREXFIO REMS.

Elranatamab’s efficacy was evaluated in MagnetisMM-3 (NCT04649359), a Phase 2, open-label, single-arm, multi-center study that included patients with r/r MM who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody. Patients had measurable disease by International Myeloma Working Group (IMWG) criteria at enrollment. The main efficacy outcome measures were objective response rate (ORR) and duration of response (DOR), as assessed by a blinded independent central review based on IMWG criteria. The primary efficacy population consisted of 97 patients naïve to prior BCMA-directed therapy and who had previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The ORR in the 97 patients receiving the recommended dose was 57.7% (95% CI: 47.3%, 67.7%). With a median follow-up of 11.1 months among responders, the median DOR was not reached (95% CI: 12 months, not reached). The DOR rate at 6 months was 90.4% (95% CI: 78.4%, 95.9%) and at 9 months was 82.3% (95% CI: 67.1%, 90.9%).

FDA’s BLA review was conducted under Project Orbis, which provides a framework for concurrent submission and review of oncology drugs among international partners. The Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Swissmedic collaborated with FDA in the review process, and are continuing to review marketing applications for elranatamab.

Interested in data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

RYSTIGGO® (rozanolixizumab-noli) approved by FDA

June 27, 2023 by Janice Reichert

On June 27, 2023, the US Food and Drug Administration approved RYSTIGGO® (rozanolixizumab-noli) for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor or anti-muscle-specific tyrosine kinase antibody positive. Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor, resulting in the reduction of circulating IgG. The drug is administered by subcutaneous infusion. UCB has indicated that rozanolixizumab-noli will be commercially available in the US during the 3rd quarter of 2023.

FDA’s approval is supported by safety and efficacy data from the pivotal Phase 3 MycarinG study (NCT03971422), published in The Lancet Neurology in May 2023. The primary efficacy endpoint was the comparison of the change from baseline between treatment groups in the MG-ADL total score at day 43. MG-ADL is a measurement tool which assesses the impact of gMG on daily functions of 8 signs or symptoms that are typically affected in gMG, such as breathing, talking, swallowing, and being able to rise from a chair. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment. A statistically significant difference favoring rozanolixizumab-noli was observed in the MG-ADL total score change from baseline [-3.4 points in rozanolixizumab-noli-treated group at either dose vs -0.8 points in the placebo-treated group (p<0.001)].

Interested in data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

Columvi® (glofitamab-gxbm) approved by FDA

June 16, 2023 by Janice Reichert

On June 15, 2023, the U.S. Food and Drug Administration (FDA) approved Columvi® (glofitamab-gxbm) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response in the Phase 1/2 NP30179 study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Glofitamab (RO7082859, CD20-TCB, RG6026) is a full-length IgG1λ/ҡ bispecific T cell-redirecting antibody targeting CD20 on malignant B cells and CD3 on T cells. This bispecific antibody was developed by Roche using the 2:1 CrossMab technology, characterized by 3 antigen-binding fragment (Fab) arms enabling monovalent binding to CD3ɛ and bivalent binding to CD20, with the second CD20 arm fused to the CD3ɛ-binding arms via a flexible linker. Glofitamab also features a heterodimeric Fc region engineered with PG LALA mutations to abolish binding to FcɣRs and C1q.

The FDA accelerated approval is based on positive results from the Phase 1/2 NP30179 study of Columvi given as a fixed course for 8.5 months in 132 patients with DLBCL who had relapsed or were refractory to prior therapies, including 30% who had received prior CAR T-cell therapy. Additionally, 83% were refractory to their most recent therapy. Results showed patients treated with fixed-duration Columvi achieved durable remission, with 56% of patients achieving an overall response (OR; 74/132 [95% confidence interval (CI): 47-65]) and 43% of patients achieving a complete response (CR; 57/132 [95% CI: 35-52]). Over two-thirds of those who responded continued to respond for at least nine months (68.5% [95% CI: 56.7-80.3]). The median duration of response was 1.5 years (18.4 months [95% CI: 11.4-not estimable]). Data from the NP30179 study were recently published in the New England Journal of Medicine.

Columvi received its first worldwide approval in Canada in March 2023, and the European Medicines Agency’s Committee for Medicinal Products for Human Use recently granted a positive opinion recommending its approval in the European Union.

Glofitamab is under investigation in a randomized, open-label, multicenter Phase 3 study (STARGLO, NCT04408638) where patients with relapsed or refractory DLBCL receive glofitamab or rituximab in combination with gemcitabine + oxaliplatin (GemOx). Patients will receive up to 8 cycles of glofitamab IV or rituximab IV in combination with GemOx IV followed by up to 4 cycles of glofitamab monotherapy. The primary outcome measure is overall survival. The estimated study primary completion date is in April 2025.

FDA approves bispecific antibody EPKINLY™ (epcoritamab-bysp)

May 19, 2023 by Janice Reichert

On May 19, 2023, the US Food and Drug Administration approved EPKINLY™ (epcoritamab-bysp) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B‑cell lymphoma, after two or more lines of systemic therapy. Created using Genmab’s DuoBody® technology, epcoritamab (GEN3013, DuoBody®-CD3xCD20) is a T cell-engaging bispecific IgG1k/l antibody targeting CD20 and CD3 that is jointly owned by Genmab and AbbVie. EPKINLY was approved under FDA’s accelerated approval program based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).

FDA’s approval was supported by data from the pivotal Phase 1/2 EPCORE NHL-1 trial (NCT03625037) studying epcoritamab in 157 patients with relapsed or refractory large B-cell lymphoma who had received at least two prior systemic therapies, including some who had received prior treatments with CAR-T cell therapy. The dose escalation findings from the Phase 1 part identified a dose of 48 mg as the recommended Phase 2 dose. In the Phase 2 part, patients received 48 mg of epcoritamab as 1 ml subcutaneous injections in 28-day cycles, with weekly dosing in Cycles 1-2, dosing every second week in Cycles 3-6, and dosing every 4 weeks from Cycle 7 onward. An overall response (complete or partial response) was seen in 61% (90/148 [95 percent confidence interval (CI): 52.5-68.7]) of patients and 38% (56/148 [95 percent CI: 30.0-46.2]) achieved complete remission. The median duration of response was 15.6 months (95 percent CI: 9.7-Not reached).

Epcoritamab is being investigated in multiple ongoing clinical studies across different settings and histologies. The most advanced of these is the randomized, open-label Phase 3 EPCORE™DLBCL-1 trial (NCT04628494) of epcoritamab vs investigator’s choice chemotherapy in patients with R/R DLBCL. The study is recruiting an estimated 552 patients and has an estimated primary completion date in June 2024.