Food and Drug Administration Archives

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.

FDA approves TALVEY™ (talquetamab-tgvs)

August 10, 2023 by Janice Reichert

On August 9, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval of TALVEY™ (talquetamab-tgvs), a first-in-class bispecific antibody for the treatment of adult patients 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 antibody. This indication is approved under accelerated approval based on response rate and durability of response, and continued approval for this indication is contingent upon verification and description of clinical benefit in confirmatory trial(s).

TALVEY™ is approved as a weekly or biweekly subcutaneous (SC) injection after an initial step-up phase. The TALVEY™ prescribing information includes a Boxed Warning for cytokine release syndrome and neurologic toxicity. The drug is available only through a restricted program called the TECVAYLI® and TALVEY™ Risk Evaluation and Mitigation Strategy

Talquetamab (JNJ-64407564) is a humanized, hinge-stabilized IgG4k/l T-cell engaging bispecific antibody with reduced effector function developed by Janssen. The antibody targets G protein-coupled receptor class C group 5 member D (GPRC5D), which is highly expressed in malignant plasma cells, and CD3 on T cells. TALVEY™ was granted Orphan Drug Designation for the treatment of MM by the U.S. FDA and the European Commission. The drug was also granted Breakthrough Therapy designation by the FDA for use in patients with r/r MM based on results of the MonumenTAL-1 study.

FDA’s approval was based on the single-arm, open-label, multicenter MonumenTAL-1 study (NCT03399799, NCT04634552), which evaluated the efficacy of TALVEY monotherapy in patients with r/r MM. Patients treated with the weekly dosing schedule received step-up doses of 0.01 mg/kg and 0.06 mg/kg of TALVEY followed by TALVEY 0.4 mg/kg subcutaneously weekly thereafter. Patients treated with the biweekly dosing schedule received step-up doses of 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg (0.75 times the recommended step-up dose 3) of TALVEY followed by TALVEY 0.8 mg/kg subcutaneously biweekly, thereafter. Patients on both dosing schedules were treated until disease progression or unacceptable toxicity. According to the prescribing information, at the SC biweekly dose of 0.8 mg/kg, 73.6% of patients (95% Confidence Interval [CI], range, 63.0 to 82.4) achieved an overall response rate (ORR). With a median follow-up of nearly 6 (range, 0 to 9.5) months from first response among responders, 58% of patients achieved a very good partial response (VGPR) or better, including 33% of patients achieving a complete response (CR) or better. At the SC weekly dose of 0.4 mg/kg, 73.0% of patients (95% CI, range, 63.2 to 81.4) achieved an ORR. With a median follow-up of nearly 14 (range, 0.8 to 15.4) months from first response among responders, 57% of patients achieved a VGPR or better, including 35% of patients achieving a CR or better. Responses were durable with a median duration of response not reached in the 0.8 mg/kg SC biweekly dose group and 9.5 months in the 0.4 mg/kg SC weekly dose group. Among patients receiving the 0.8 mg/kg SC biweekly dose, an estimated 85% of responders maintained response for at least 9 months.

Talquetamab is being evaluated in a randomized Phase 3 study (MonumenTAL-1; NCT05455320) comparing the efficacy of talquetamab SC in combination with daratumumab SC or in combination with daratumumab and pomalidomide vs daratumumab SC in combination with pomalidomide and dexamethasone in patients with r/r MM. Initiated in October 2022, the study has an estimated enrollment of 810 and an estimated primary completion date in February 2026.

FDA approves Beyfortus (nirsevimab-alip)

July 17, 2023 by Janice Reichert

On July 17, 2023, the U.S. Food and Drug Administration (FDA) approved Beyfortus (nirsevimab-alip) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Beyfortus is a human IgG1ҡ antibody targeting RSV. Developed by AstraZeneca and Sanofi, the Fc domain was engineered using AstraZeneca’s proprietary YTE half-life extension technology. One dose of Beyfortus, administered as a single intramuscular injection prior to or during RSV season, may provide protection during the RSV season.

Beyfortus has been granted special designations to facilitate expedited development by several regulatory agencies. These include Breakthrough Therapy Designation and Priority Review designation by The China Center for Drug Evaluation under the National Medical Products Administration; Breakthrough Therapy Designation from the U.S. Food and Drug Administration; access granted to the European Medicines Agency (EMA) PRIority MEdicines (PRIME) scheme and EMA accelerated assessment; Promising Innovative Medicine designation by the UK Medicines and Healthcare products Regulatory Agency; and has been named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development.

Beyfortus has been granted marketing authorization in the European Union, Great Britain and Canada for the prevention of RSV lower respiratory tract disease in newborns and infants from birth through their first RSV season and is currently undergoing regulatory review in China, Japan and several other countries. In Canada, nirsevimab is also approved for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season, and such indication is under review at the EMA level.

The safety and efficacy of Beyfortus were supported by three clinical trials (Trials 03, 04 and 05). The key measure of efficacy was the incidence of medically attended RSV lower respiratory tract infection (MA RSV LRTI), evaluated during the 150 days after Beyfortus administration. MA RSV LRTI included all health care provider visits (physician office, urgent care, emergency room visits and hospitalization) for lower respiratory tract disease with worsening clinical severity and a positive RSV test. Trials 03 and 04 were randomized, double-blind, placebo-controlled, multicenter clinical trials.

Trial 03 (Phase 2b study, NCT02878330) included 1,453 preterm infants (born at greater than or equal to 29 weeks of gestational age up to less than 35 weeks of gestation) who were born during or entering their first RSV season. Of the 1,453 preterm infants in the trial, 969 received a single dose of Beyfortus and 484 received placebo. Among infants who were treated with Beyfortus, 25 (2.6%) experienced MA RSV LRTI compared with 46 (9.5%) infants who received placebo. Beyfortus reduced the risk of MA RSV LRTI by approximately 70% relative to placebo. The Beyfortus dosing regimen was determined based on further exploration of the Phase 2b data and was used in subsequent trials as a single 50 mg dose for those who weigh less than 5 kg, or a single 100 mg dose for those who weigh 5 kg or greater

For Trial 04 (Phase 3 MELODY study, NCT03979313), the primary analysis group within the trial included 1,490 term and late preterm infants (born at greater than or equal to 35 weeks in gestational age), 994 of whom received a single dose of Beyfortus and 496 of whom received placebo. The primary endpoint was met, reducing the incidence of medically attended RSV LRTD by 74.9% (95% CI 50.6, 87.3; P<0.001) compared to placebo. Among infants who were treated with Beyfortus, 12 (1.2%) experienced MA RSV LRTI compared with 25 (5.0%) infants who received placebo.

Trial 05 (Phase 2/3 MEDLEY study, NCT03959488), a randomized, double-blind, active (palivizumab)-controlled, multicenter trial, supported the use of Beyfortus in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. The trial enrolled 925 preterm infants and infants with chronic lung disease of prematurity or congenital heart disease. The safety and pharmacokinetic data from Trial 05 provided evidence for the use of Beyfortus to prevent MA RSV LRTI in this population.

References

Trial 03: Griffin MP, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med. 2020;383(5):415-425. doi: 10.1056/NEJMoa1913556.

Trial 04: Hammitt LL, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med. 2022;386(9):837-846. doi:10.1056/NEJMoa2110275.

Trial 05: Domachowske J, et al. Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity. N Engl J Med. 2022;386(9):892-894. doi:10.1056/NEJMc2112186.

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.