FDA Drug Approvals Q2 2024

Hematology/oncology

Imdelltra (tarlatamab)

Tarlatamab is a bispecific T-cell engager (BiTE) that binds to delta-like ligand 3 (DLL3) expressed on the surface of cells, including tumor cells, and CD3 expressed on the surface of T cells. Binding causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells.

Tarlatamab gained accelerated approval from the FDA for adults with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. 

Approval was based on the Phase 2 DeLLphi-301 study (N = 99). Patients received an initial 1-mg dose followed by 10 mg on Days 8, 15, and every 2 weeks thereafter until disease progression or unacceptable toxicity. Overall response rate (ORR) was 40% (complete response 2% and partial response 38%). Of 69 patients with available data regarding platinum sensitivity status, the ORR was 52% in 27 patients with platinum-resistant SCLC and 31% in an additional 42 patients with platinum-sensitive SCLC. Median duration of response was 9.7 months (> 6 months 68%; > 12 months 40%). N Engl J Med. 2023 Nov 30;389(22):263-2075

Ojemda (tovorafenib)

Tovorafenib is indicated for relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation, in young adults and pediatric patients aged 6 months and older. 

Data were assessed in 137 patients participating in the Phase 2 FIREFLY-1 trial according to the Pediatric Neuro-oncology Low-grade Glioma (RAPNO) criteria. The overall response (including minor responses) was 51%, median duration of response was 13.8 months, and median time to response was 5.3 months. Nat Med. 2024;30(1):207-217

Anktiva (nogapendekin alfa inbakicept)

Nogapendekin alfa inbakicept, an interleukin-15 (IL-15) agonist, is indicated in combination with BCG for intravesical treatment of adults with BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. Binding of nogapendekin alfa inbakicept to its receptor results in proliferation and activation of NK, CD8+, and memory T cells without proliferation of immunosuppressive regulatory T cells (TREG).

Approval was supported by results from the Phase 2/3 QUILT-3.032 trial (N = 77). Complete response (CR) was 62%. The duration of CR was 12 months or longer in 58% of patients, and 24 months or longer in 40% of patients. Urol Pract. 2024 Mar; 11(2):367-375

Rytelo (imetelstat)

Imetelstat is an oligonucleotide telomerase inhibitor indicated for adults with transfusion-dependent myelodysplastic syndrome (MDS) who have not responded to, have lost response to, or are ineligible for ESAs. Inhibiting telomerase enzymatic activity leads to reduced telomere length, reduced malignant stem and progenitor cell proliferation, and induction of apoptotic cell death.

Approval was based on results from the multicenter, randomized, double-blind, placebo-controlled Phase 3 IMerge trial (N = 178). Trial participants had a low or intermediate MDS risk and required 4 or more RBC units over an 8-week period during the 16 weeks before randomization. The proportion of patients who did not require RBC transfusion(s) during any consecutive 8-week (56 days) period was significantly higher in the imetelstat arm compared with the placebo arm (40% vs 15%; P = 0.0008). Lancet. 2024 Jan 20;403(10423):249-260

Lumisight (pegulicianine)

Pegulicianine is a fluorescence-guided visualization system. It is indicated for adults with breast cancer as an adjunct for intraoperative detection of cancerous tissue within the resection cavity following removal of the primary specimen during lumpectomy surgery.

Approval was supported by a pilot feasibility trial and a prospective margin status trial. In 27 of 357 patients, pegulicianine-guided margins assessment removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided in 9 of 62 patients with positive margins. JAMA Surg. 2022 Jul1;157(7):573-580, NEJM Evid. 2023 Jul;2(7):EVIDoa2200333

Xolremdi (mavorixafor)

Mavorixafor is indicated for WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome in patients aged 12 years and older to increase amount of circulating mature neutrophils and lymphocytes. It is an orally bioavailable inhibitor of CXC chemokine receptor type 4 (CXCR4), with potential antineoplastic and immune checkpoint inhibitory activities. Mutations in the CXCR4 receptor gene that occur in patients with WHIM syndrome lead to increased responsiveness to CXCL12 and retention of leukocytes in the bone marrow. Treatment with mavorixafor results in increased mobilization of neutrophils and lymphocytes from the bone marrow into peripheral circulation.

Approval was supported by a global phase 3 trial. Results in 31 participants (mavorixafor, n = 14; placebo, n = 17) showed statistically significant improvement in the time (hours) above ANC threshold (TATANC). Mavorixafor mean TATANC was 15 hours compared with placebo of 2.8 hours (P < 0.001).

Higher absolute WBC, ANC, and ALC levels were seen with mavorixafor than placebo at each time point assessed. Annualized infection rates were 60% lower with mavorixafor versus placebo (1.7 vs 4.2; P = 0.007) and total infection scores were 40% lower (7.4 vs 12.3). Blood. 2024 Apr 21:blood.2023022658

Beqvez (fidanacogene elaparvovec)

Fidanacogene elaparvovec is an adeno-associated virus vector-based one-time gene therapy indicated for treatment of adult males with moderate-to-severe hemophilia B (congenital factor IX [FIX]) deficiency.

It is indicated in patients who:

• Currently use factor IX prophylaxis therapy, or

• Have current or historical life-threatening hemorrhage, or

• Have repeated, serious spontaneous bleeding episodes, and,

• Do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test

Results from the ongoing, prospective, open-label, single-arm, global Phase 3 BENEGENE-2 study (N = 45 males) supported the approval. The main objective was to evaluate the annualized bleeding rate (ABR) of the gene therapy versus factor IX (FIX) prophylaxis.

Fidanacogene elaparvovec was noninferior in the ABR of total bleeds post infusion versus prophylaxis regimen with FIX, administered as part of usual care. A mean ABR of 2.5 was observed among patients who received fidanacogene elaparvovec in the efficacy evaluation period (defined as between Week 12 and data cutoff [median 1.8 years of follow-up]) compared with a mean ABR of 4.5 during the lead-in pretreatment period of at least 6 months (median 1.2 years of follow-up). Bleeds were eliminated in 60% of patients​​ compared to 29% in the prophylaxis arm. Prescribing Information

Piasky (crovalimab)

Crovalimab is a monoclonal antibody that binds to complement protein C5, resulting in inhibiting its cleavage into C5a and C5b and preventing formation of membrane attack complex (MAC). This inhibits terminal complement-mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). It was approved in June 2024 for patients aged 16 years and older with PNH.

Approval was supported by the Phase 3 COMMODORE 2 and COMMODORE 3 clinical trials. In COMMODORE 2 (N = 204), crovalimab was shown to be noninferior to eculizumab for hemolysis control (79.3% vs 79%). Am J Hematol. 2024 Jun 17

In the single-arm COMMODORE 3 study, 51 complement-naïve patients showed significant hemolysis control and transfusion avoidance from baseline through Week 25 (P < 0.001). Am J Hematol. 2023 Sep. 98 (9):1407-1414

Other hematology/oncology approvals

Enhertu (trastuzumab deruxtecan) – New indication for unresectable or metastatic HER2-positive (IHC 3+) solid tumors

Augtyro (repotrectinib) – New indication for patients aged 12 years and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion

Imfinzi (durvalumab) – Indicated in combination with chemotherapy for patients with primary, advanced, or recurrent endometrial cancer that is mismatch repair deficient (dMMR)

Keytruda (pembrolizumab) – Indicated with carboplatin and paclitaxel, followed by single-agent pembrolizumab for adults with primary advances or recurrent endometrial carcinoma

Krazati (adagrasib) – New indication approved for KRAS G12C-mutated locally advanced or metastatic colorectal cancer

Alecensa (alectinib) – Indicated as adjuvant treatment after tumor resection for ALK+ NSCLC

Lutathera (lutetium Lu 177-dota-tate) – Indication for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors expanded to include children aged 12 years and older

Abecma (idecabtagene vicleucel) – Indication for multiple myeloma revised to allow for earlier use after 2 prior lines of therapy

Carvykti (ciltacabtagene autoleucel) – Indication for multiple myeloma revised to allow for earlier use after at least 1 prior line of therapy

Breyanzi (lisocabtagene maraleucel) – New indication approved for relapsed or refractory follicular lymphoma and mantle cell lymphoma in patients who have received at least 2 prior lines of systemic therapy

Blincyto (blinatumomab) – New indication for treatment of adult and pediatric patients aged 1 month and older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL)

Epkinly (epcoritamab) – FDA grants accelerated approval for relapsed/refractory follicular lymphoma

Xromi (hydroxyurea) – Oral solution approved for infants aged 6-24 months to reduce frequency of painful sickle cell crises and need for blood transfusions

Retevmo (selpercatinib)

• Indications expanded for medullary thyroid cancer and thyroid cancer to include children aged 2 years and older (previously approved for children aged 12 years and older)

• Indication for solid tumors with RET gene fusion expanded to include children aged 2 years and older (previously approved for adults)

Bkemv (eculizumab) is an interchangeable biosimilar to Soliris for:

• Adults with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, and

• Adults and children with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy

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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: Mary L. Windle. FDA Drug Approvals Q2 2024 - Medscape - Jul 05, 2024.