FDA First Half Recap: Novel Drug Approvals

Welcome to the first edition of the Provider's Digest, a monthly LinkedIn newsletter spotlighting FDA news brought to you by the editorial team of HCPLive. A member of the MJH Life Sciences® family of brands, our monthly newsletter will spotlight clinically relevant approvals, clearances, CRLs, and other regulatory decisions from the US Food and Drug Administration from across nearly 2 dozen specialties in medicine.

To celebrate our inaugural edition of this newsletter and the innovation that has defined healthcare through the first 6 months of 2024, we are recapping the 20 novel drug approval from the FDA during the first half of the year, with links to accompanying coverage from ourselves and other MJH Life Sciences brands, including OncLive, Contemporary OB/GYN, Contemporary Pediatrics, Contagion_Live, and more!

Novel Drug Approvals Recap: First Half 2024

1. Berdazimer (Zelsuvmi)

Date: January 05, 2024

Indication: Molluscum Contagiosum

Background: Approval of berdazimer gel 10.3% was awarded to Ligand Pharmaceuticals based on the B-SIMPLE4 trial. The 891-patient, multicenter, vehicle-controlled, double-blind, phase 3 randomized clinical trial met its primary endpoint of complete clearance of molluscum contagiosum lesions at week 12 versus vehicle.

Related Coverage: FDA Approves Topical Berdazimer Gel for Molluscum Contagiosum

2. Cefepime/Enmetazobactam (Exblifep)

Date: February 22, 2024 Indication: Complicated Urinary Tract Infections

Background: Approval of cefepime/enmetazobactam was awarded to Allecra Therapeutics based on data from a phase 3 trial comparing it against piperacillin/tazobactam among 1041 patients. Results indicated a greater proportion of patients treated with cefepime/enmetazobactam achieved composite response defined as clinical cure and microbiological eradication at the test-of-cure visit on day 7 than those receiving piperacillin/tazobactam.

Related Coverage: FDA Approves Enmetazobactam for Treatment of cUTIs

3. LetibotulinumtoxinA-wlb (Letybo)

Date: February 29, 2024

Indication: Temporarily Improve the Appearance of Moderate-to-Severe Glabellar Lines

Background: Approval of letibotulinumtoxinA-wlb was awarded to Hugel Inc based on data from a trio of clinical trials referred to as the BLESS program. With a population of 1271 adults patients aged 18 to 75 years with moderate to severe glabellar lines, results indicated use was associated with a greater proportion of patients achieving achieving a score of 0 or 1 (none or mild) and at least a 2-grade improvement of wrinkles between the eyebrows at maximum frown from baseline to week 4 relative to placebo.

Related Coverage: Putting Education and Innovation at the Forefront at Winter Clinical Miami

4. Tislelizumab-jsgr (Tevimbra)

Date: March 13, 2024

Indication: Unresectable or Metastatic Esophageal Squamous Cell Carcinoma

Background: Approval of tislelizumab-jsgr was awarded to BeiGene based on the RATIONALE 302 study. A phase 3 trial of 562 patients with unresectable or metastatic esophageal squamous cell carcinoma with a history of prior systemic chemotherapy, results indicated use of tislelizumab significantly improved overall survival compared to chemotherapy.

Related Coverage: FDA Approves Tislelizumab for Advanced or Metastatic ESCC After Chemotherapy

5. Resmetirom (Rezdiffra)

Date: March 14, 2024

Indication: Noncirrhotic Non-Alcoholic Steatohepatitis (NASH) with Moderate to Advanced Liver Scarring

Background: Approval of resmetirom was awarded to Madrigal Pharmaceuticals based on the MAESTRO-NASH trial. The first FDA-approved medication to receive this indication, the pivotal trial of resmetirom concluded use was associated greater NASH resolution with no worsening of fibrosis among a population of 966 adult patients with NASH and fibrosis.

Related Coverage: HCPLive Special Report: How Approval of Resmetirom Impacts Management, Screening for NASH

6. Aprocitentan (Tryvio)

Date: March 19, 2024

Indication: Hypertension

Background: Approval of aprocitentan was awarded to Idorsia Ltd based on the phase 3 PRECISION trial. The 730-patient trial concluded use of aprocitentan was associated with greater change in office systolic blood pressure than placebo therapy. The approval marked the first time the FDA had approved an oral antihypertensive agent with a new mechanism of action in more than 30 years.

Related Coverage: What to Know about the Aprocitentan Approval for Resistant Hypertension, with Michael Weber, MD

7. Givinostat (Duvyzat)

Date: March 21, 2024

Indication: Duchenne Muscular Dystrophy (DMD) in Individuals Aged 6 years and Older

Background: Approval of givinostat was awarded to Italfarmaco SpA based on the EPIDYS trial. A 179-patient, phase 3 trial of male patients with DMD, the trial met its primary endpoint of change from baseline to month 18 in 4-stair climb (4SC) assessment time.

Related Coverage: FDA Approves Givinostat for Duchenne Muscular Dystrophy in Patients 6 Years and Up

8. Sotatercept-csrk (Winrevair)

Date: March 26, 2024

Indication: Pulmonary Arterial Hypertension

Background: Approval of sotatercept was awarded to Merck based on the STELLAR trial. A 323-patient, phase 3 trial, results indicated use of sotatercept was associated with a greater change from baseline in 6-minute walking distance from baseline to week 24 relative to placebo therapy.

Related Coverage: FDA Approves Sotatercept (Winrevair) for Pulmonary Arterial Hypertension

9. Vadadustat (Vafseo)

Date: March 27, 2024

Indication: Anemia Due to Chronic Kidney Disease

Background: Approval of vadadustat was awarded to Akebia Therapeutics based on data from the INNO2VATE program and an assessment of post-marketing safety data from Japan where vadadustat was launched in August 2020.

Related Coverage: FDA Approves Vadadustat (Vafseo) Tablets for Anemia Due to CKD in Adult Patients on Dialysis

10. Danicopan (Voydeya)

Date: March 29, 2024

Indication: Extravascular Hemolysis with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Background: Approval of danicopan was awarded to AstraZeneca based on the ALPHA trial. Results of the indicated treatment with danicopan met the trial’s primary endpoint of increased hemoglobin levels from baseline to week 12 relative to placebo therapy.

Related Coverage: FDA Approves Danicopan as Add-On Therapy for Extravascular Hemolysis in PNH

11. Ceftobiprole Medocaril Sodium (Zevtera)

Date: April 03, 2024

Indication: Certain Bloodstream Infections, Bacterial Skin and Associated Tissue infections, and Community-Acquired Bcterial Pneumonia

Background: Approval of ceftobiprole medocaril sodium was awarded to Basilea Pharmaceutica International based on the ERADICATE trial. A 390-patient phase 3 trial, results concluded ceftobiprole was noninferior to daptomycin for overall treatment success in patients with complicated S. aureus bacteremia.

Related Coverage: Ceftobiprole Receives FDA Approval, Enhancing Antibiotic Options

12. Pegulicianine (Lumisight)

Date: April 17, 2024

Indication: Optical Imaging Agent for the Detection of Cancerous Tissue

Background: Approval of pegulicianine was awarded to Lumicell based on the INSITE trial. Results of the trial, which assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS), concluded use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity.

Related Coverage: FDA Approves Pegulicianine-Based Imaging for Breast Cancer Surgery

13. Nogapendekin Alfa Inbakicept-pmln (Anktiva)

Date: April 22, 2024

Indication: Bladder Cancer

Background: Approval of Nogapendekin alfa inbakicept-pmln was awarded to ImmunityBio based on the QUILT-3.032 trial. An analysis of the open-label, phase 2/3 trial suggested complete responses were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer–specific survival at 24 months.

Related Coverage: FDA Approves Nogapendekin Alfa Inbakicept Plus BCG for BCG-Unresponsive NMIBC

14. Tovorafenib (Ojmeda)

Date: April 23, 2024

Indication: Relapsed or Refractory Pediatric Low-Grade Glioma

Background: Approval of tovorafenib was awarded to Day One Bio based on data from the ongoing FIREFLY-1 trial. Tovorafenib is the first agent indicated for patients with pediatric low-grade glioma.

Related Coverage: Sarah Leary, MD, MS: FDA Approval of Tovorafenib for Pediatric R/R BRAF Low-Grade Glioma

15. Mavorixafor (Xolremdi)

Date: April 26, 2024

Indication: Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) Syndrome

Background: Approval of mavorixafor was awarded to X4 Pharmaceuticals and supported by data from the 4WHIM trial. A 31-patient trial, results indicated improvement in absolute neutrophil counts, improvement in absolute lymphocyte counts, and a reduction in infections at week 52 relative to placebo. The approval marked the first indication for WHIM syndrome in FDA history.

Related Coverage: FDA Approves Mavorixafor as First Drug for WHIM Syndrome

16. Tarlatamab-dlle (Imdelltra)

Date: May 16, 2024

Indication: Extensive Stage Small Cell Lung Cancer

Background: Approval of tarlatamab was awarded to Amgen based on the DeLLphi-301 trial. Results of the phase 2, open-label, multicenter, multi-cohort trial suggested use of tarlatamab was associated with improved antitumor activity with durable objective responses and favorable survival outcomes in patients with previously treated small-cell lung cancer.

Related Coverage: Taofeek Owonikoko, MD, PhD, on the Impact of the FDA Approval of Tarlatamab in ES-SCLC

17. Imetelstat (Rytelo)

Date: June 06, 2024

Indication: Low- to Intermediate-1 Risk Myelodysplastic Syndromes

Background: Approval of imetelstat was awarded to Geron Corporation based on the IMerge trial. A 178-patient phase 3 trial, results indicated use of imetelstat was associated with a greater red blood cell transfusion independence rate among patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents.

Related Coverage: Michael Sekeres, MD, on the FDA Approval of Imetelstat in Lower-Risk MDS With Anemia

18. Elafibranor (Iqirvo)

Date: June 10, 2024

Indication: Primary Biliary Cholangitis (PBC)

Background: Approval of elafibranor was awarded to Ipsen based on the ELATIVE trial. A 161-patient double-blind, placebo-controlled, phase 3 trial, results demonstrated use of elafibranor was associated with significantly greater improvements in relevant biochemical indicators of cholestasis than placebo therapy at 52 weeks.

Related Coverage: HCPLive Special Report: Updates and Unmet Needs in PBC

19. Sofpironium (Sofdra)

Date: June 18, 2024 Indication: Primary Axillary Hyperhidrosis

Background: Approval of sofpironium topical gel 12.45% was awarded to Botanix Pharmaceuticals based on the CARDIGAN studies. A pair of phase 3 studies, both trials met all primary and secondary endpoints, with clinically and statistically meaningful changes from baseline in Gravimetric Sweat Production (GSP) and the Hyperhidrosis Disease Severity Measure-Axillary, 7-item (HDSM-AX7) score.

Related Coverage: FDA Approves Sofpironium, First Treatment for Primary axillary Hyperhidrosis

20. Crovalimab-akkz (Piasky)

Date: June 20, 2024 Indication: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Background: Approval of crovalimab was awarded to Genentech based on the COMMODORE 2 trial. A 204-patient, randomized, open-label, phase 3 trial, results indicated crovalimab was noninferior to eculizumab for both hemolysis control and transfusion avoidance.

Related Coverage: FDA Approves Crovalimab for Paroxysmal Nocturnal Hemoglobinuria

References:

1. Center for Drug Evaluation and Research. Novel drug approvals for 2024. U.S. Food and Drug Administration. June 28, 2024. Accessed June 30, 2024. https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024.

2. Browning JC, Enloe C, Cartwright M, et al. Efficacy and Safety of Topical Nitric Oxide−Releasing Berdazimer Gel in Patients With Molluscum Contagiosum: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2022;158(8):871–878. doi:10.1001/jamadermatol.2022.2721

3. Kaye KS, Belley A, Barth P, et al. Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial. JAMA. 2022;328(13):1304–1314. doi:10.1001/jama.2022.17034

4. Center for Drug Evaluation and Research. Drug trials snapshots: Letybo. U.S. Food and Drug Administration. March 22, 2024. Accessed June 30, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-letybo.

5. Shen L, Kato K, Kim S-B, et al. RATIONALE 302: randomized, phase 3 study of tislelizumab versus chemotherapy as second-line treatment for advanced unresectable/metastatic esophageal squamous cell carcinoma. J Clin Oncol. 2021;39(suppl 15):4012. doi:10.1200/JCO.2021.39.15_suppl.4012

6. Office of the Commissioner. FDA approves first treatment for patients with liver scarring due to fatty liver disease. U.S. Food and Drug Administration. March 14, 2024. Accessed June 30, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease.

7. Schlaich MP, Bellet M, Weber MA, et al. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial [published correction appears in Lancet. 2023 Jan 28;401(10373):268]. Lancet. 2022;400(10367):1927-1937. doi:10.1016/S0140-6736(22)02034-7

8. Mercuri E, Vilchez JJ, Boespflug-Tanguy O, et al. Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet Neurol. 2024 Jun;23(6):e10. doi: 10.1016/S1474-4422(24)00172-8]. Lancet Neurol. 2024;23(4):393-403. doi:10.1016/S1474-4422(24)00036-X

9. Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2023;388(16):1478-1490. doi:10.1056/NEJMoa2213558

10. Akebia Therapeutics. Akebia Receives FDA Approval of Vafseo® (vadadustat) Tablets for the Treatment of Anemia due to Chronic Kidney Disease in Adult Patients on Dialysis. March 27, 2024. Accessed March 27, 2024. https://ir.akebia.com/news-releases/news-release-details/akebia-receives-fda-approval-vafseor-vadadustat-tablets

11. Lee JW, Griffin M, Kim JS, et al. Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial. Lancet Haematol. 2023;10(12):e955-e965. doi:10.1016/S2352-3026(23)00315-0

12. Holland TL, Cosgrove SE, Doernberg SB, et al. Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia. N Engl J Med. 2023;389(15):1390-1401. doi:10.1056/NEJMoa2300220

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14. Chamie K, Chang SS, Kramolowsky E, et al. IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer. NEJM Evid. 2023;2(1):EVIDoa2200167. doi:10.1056/EVIDoa2200167

15. Kilburn LB, Khuong-Quang DA, Hansford JR, et al. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial [published correction appears in Nat Med. 2024 May;30(5):1500. doi: 10.1038/s41591-024-02910-1]. Nat Med. 2024;30(1):207-217. doi:10.1038/s41591-023-02668-y

16. Badolato R, Alsina L, Azar A, et al. Phase 3 randomized trial of mavorixafor, CXCR4 antagonist, in WHIM syndrome. Blood. Published online April 21, 2024. doi:10.1182/blood.2023022658

17. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med. 2023;389(22):2063-2075. doi:10.1056/NEJMoa2307980

18. Zeidan AM, Platzbecker U, Santini V, et al. IMerge: results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). J Clin Oncol. 2023;41(suppl 16):7004. doi:10.1200/JCO.2023.41.16_suppl.7004

19. Kowdley KV, Bowlus CL, Levy C, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. N Engl J Med. 2024;390(9):795-805. doi:10.1056/NEJMoa2306185

20. Botanix Pharmaceuticals. FDA approval of SofdraTM - the first new drug for primary axillary hyperhidrosis. Botanix Pharmaceuticals. June 20, 2024. Accessed June 30, 2024. https://botanixpharma.com/fda-approves-sofdra-topical-gel/.

21. Röth A, He G, Brodsky A, et al. S181: THE PHASE III, RANDOMIZED COMMODORE 2 TRIAL: RESULTS FROM A MULTICENTER STUDY OF CROVALIMAB VS ECULIZUMAB IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) PATIENTS NAIVE TO COMPLEMENT INHIBITORS. Hemasphere. 2023;7(Suppl ):e72750f1. Published 2023 Aug 8. doi:10.1097/01.HS9.0000967636.72750.f1