December 2023 decisions expected from the FDA

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs likely to be approved by the U.S. Food and Drug Administration (FDA).

Drug pipeline for December 2023:

4Q2023: capivasertib
The FDA has granted Priority Review for AstraZenaca’s capivasertib, for use with Faslodex^® (fulvestrant) to treat adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine-based regimen. In the Phase 3 CAPItello-291 (NCT04305496) trial, the combination therapy led to a 40% reduction is risk of disease progression or death compared to Faslodex alone (median progression-free survival, 7.2 versus 3.6 months, respectively; p<0.001).¹ If approved, capivasertib will be a first-in-class oral AKT (serine/threonine kinase) inhibitor available in the U.S.

4Q2023: tislelizumab
BeiGene expects an FDA decision in 2023 for tislelizumab for second-line unresectable, recurrent, locally advanced, or metastatic esophageal squamous cell carcinoma (ESCC). Tislelizumab is a humanized immunoglobulin G4 (IgG4) anti-programmed death-ligand 1 (PD-1) monoclonal antibody. In the Phase 3 RATIONALE-302 (NCT03430843) trial, tislelizumab significantly increased overall survival compared to single-agent chemotherapy in all patients (median, 8.6 versus 6.3 months; respectively; p=0.0001), and in patients with PD-L1 tumor area positivity (TAP) ≥ 10% (median, 10.3 months versus 6.8 months, respectively; p=0.0006).² If approved, tislelizumab, an orphan drug, will provide a third programmed death 1 (PD-1) inhibitor option as second-line therapy in patients with unresectable, recurrent, locally advanced, or metastatic ESCC, competing with Opdivo^® (nivolumab) and Keytruda^® (pembrolizumab).

12/06/2023: denosumab biosimilar  (GP-2411)
The FDA is reviewing Sandoz’s biologics license application (BLA) for a denosumab biosimilar.³ If approved, it will be the first biosimilar to the reference medicines by Amgen, Xgeva^® and Prolia^®. In the U.S., biosimilars are highly similar to and have no clinically meaningful differences from their reference product. The application submitted to the FDA includes all indications covered by the reference products. Prolia is indicated for the treatment of osteoporosis in men and postmenopausal women, treatment of glucocorticoid-induced osteoporosis in men and women, and to increase bone mass in women on aromatase inhibitor therapy or men receiving androgen deprivation therapy; all indicated populations are high risk for fracture. Xgeva is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors, treatment of select patients with giant cell tumor of bone, and treatment of hypercalcemia of malignancy that is refractory to bisphosphonate therapy.

12/08/2023: exagamglogene autotemcel (exa-cel)
The FDA has granted a Priority Review for the gene therapy, exa-cel by Vertex and CRISPR, for the treatment of severe sickle cell disease (SCD).⁴ Exa-cel treats the underlying cause of SCD by genetically modifying a patients hematopoietic stem cells (HSCs), using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-9 technology, to produce product red blood cells (RBCs) with high levels of fetal hemoglobin (HbF). In CLIMB-SCD-121 (NCT03745287), a single-arm, open-label, phase 1/2/3 trial, 94.1% of patients treated with a single intravenous (IV) infusion of exa-cel achieved freedom from vaso-occlusive episodes (VOEs) for ≥ 12 months. The mean duration of freedom from VOEs was 18.7 months (maximum 36.5 months). No serious treatment-related adverse events were reported with exa-cel. The FDA designated exa-cel as an Orphan Drug, Rare Pediatric Disease agent, and Regenerative Medicine Advanced Therapy. If approved, exa-cel would become one of the gene therapies, along with lovotibeglogene autotemcel, to treat SCD with a single dose.

12/15/2023: trastuzumab biosimilar (HLX02)
Henlius and Accord are seeking FDA approval of their trastuzumab biosimilar to Genentech’s Herceptin^®, an IV-administered HER2/neu receptor antagonist indicated for the treatment of HER2-overexpressing breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.⁵ If approved, Henlius and Accord’s trastuzumab biosimilar will be the sixth biosimilar for Herceptin approved by the FDA.

12/16/2023: roflumilast 0.3% foam (ARQ-154)
The FDA is reviewing Arcutis’ selective phosphodiesterase type 4 (PDE4) inhibitor roflumilast foam for the treatment of seborrheic dermatitis in individuals ≥ 9 years of age.⁶ In the Phase 3, STRATUM (NCT04973228) trial, 79.5% of patients who were treated with roflumilast foam experienced treatment success compared to 58% who received vehicle (p<0.0001) at week eight. In addition, 51.3% of those treated with roflumilast foam achieved complete clearance at week eight.

12/19/2023: aprocitentan
Idorsia has submitted a new drug application (NDA) to the FDA for aprocitentan, a dual endothelin receptor antagonist, for the treatment of resistant hypertension. In the Phase 3 PRECISION (NCT03541174) trial, at 4 weeks, the addition of once-daily oral doses of aprocitentan 12.5mg and 25mg to background antihypertensive therapy reduced office systolic and diastolic blood pressure in adults with resistant hypertension compared to placebo (placebo-adjusted SBP change, -3.8 mm Hg and -3.7 mm Hg, respectively; placebo-adjusted  DBP change, -3.9 mm Hg and -4.5 mm Hg, respectively).⁷ If approved, aprocitentan will be the first dual endothelin receptor antagonist to treat resistant hypertension. Notably, its effect on cardiovascular outcomes have not been established.

12/20/2023: lovotibeglogene autotemcel (lovo-cel)
The FDA has granted a Priority Review for the gene therapy, lovo-cel by bluebird bio for the treatment of severe SCD in patients with a history of VOEs.⁸ Lovo-cel treats the underlying cause of SCD by genetically altering a patient’s HSCs with the addition of functional copies of a modified β-globin gene (βA-T87Q-globin gene). The resulting cells are designed to reduce RBC sickling and hemolysis. In the single-arm, phase 1/2 HGB-206 trial (NCT02140554), 31 patients (96%) who received a single IV infusion of lovo-cel experienced complete resolution of severe VOEs through 24 months of follow-up.⁸ The safety profile for lovo-cel was generally consistent the hematopoietic stem and progenitor cell collection and busulfan conditioning regimen. The FDA designated lovo-cel as an Orphan Drug, Rare Pediatric Disease agent, and Regenerative Medicine Advanced Therapy. If approved, lovo-cel would become one of the gene therapies, along with exa-cel, to treat SCD with a single dose.

12/21/2023: givinostat
The FDA is conducting a Priority Review of givinostat, a histone deacetylases (HDACs) inhibitor, for the treatment of Duchenne muscular dystrophy (DMD).⁹ The Phase 3, EPIDYS (NCT02851797) trial evaluated givinostat in ambulant boys ≥ 6 years of age with DMD who were on stable corticosteroid therapy. The study demonstrated a slower decline from baseline to climb four stairs with twice daily givinostat oral suspension compared to placebo (difference versus placebo, 1.78 seconds; p=0.0345). Significant improvements in the secondary endpoints of North Star Ambulatory Assessment (NSAA) (p=0.02) and the time to rise test were also reported with givinostat compared to placebo. If approved, givinostat, by Italfarmaco, will be an additional option in the growing armamentarium for DMD. The FDA has granted givinostat Orphan Drug and Rare Pediatric Disease designations.

12/22/2023: eplontersen
Eplontersen is a ligand-conjugated antisense (LICA) agent by Ionis and AstraZeneca that inhibits the production of the transthyretin (TTR) protein. The FDA is reviewing eplontersen for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy (hATTRv-PN). In the Phase 3 NEURO-TTRansform (NCT04136184) study, eplontersen significantly reduced TTR concentration, halted progression of neuropathy, and improved quality of life at 66 weeks.¹⁰ If approved, eplontersen will be the fourth TTR-targeting antisense to treat hATTRv-PN, following approval of inotersen (Tegsedi^®; 2018), patisiran (Onpattro^®; 2018), and vutrisiran (Amvuttra^®; 2022). The Orphan Drug is a subcutaneous injection that is self-administered every four weeks.

12/22/2023: travoprost ocular implant (iDose-TR)
The FDA is reviewing Glaukos’ travoprost ocular implant under their 505(b)(2) pathway for the treatment of open-angle glaucoma or ocular hypertension.¹¹ In two Phase 3 trials (NCT03519386, NCT03868124), iDose-TR demonstrated non-inferiority to twice-daily timolol 0.5% ophthalmic drops, based on diurnal intraocular pressure (IOP) measurements, for up to three months. iDose-TR is designed to be removed and replaced every 12 months to provide long-term treatment without the need for daily eye drops. It may offer an alternative for patients who struggle with administering multiple daily eyedrops.

12/23/2023: insulin glargine biosimilar (Basalin)
Gan & Lee is seeking FDA approval of their biosimilar to Lantus^® (insulin glargine), a long-acting insulin analog that is approved for the treatment of types 1 and 2 diabetes mellitus.¹² In two clinical trials, the proposed biosimilar demonstrated comparable safety, efficacy, and immunogenicity to its reference product. If approved, commercialization by Sandoz is planned in the U.S.

12/27/2023: gefapixant
The FDA is reviewing gefapixant by Merck for the treatment of chronic cough. The oral selective P2X3 receptor antagonist was evaluated in two Phase 3 trials, COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147).¹³ Twice daily doses of gefapixant 45mg demonstrated a statistically significant reduction in 24-hour cough frequency compared to placebo at week 12 in COUGH-1 (reduction relative to placebo, 18.45%; p=0.041), and at week 24 in COUGH-2 (reduction relative to placebo, 14.64%; p=0.031). Taste disturbances were reported with gefapixant. If approved, gefapixant will be the first medication approved in the U.S. that is indicated specifically for refractory or unexplained chronic cough.

References

1. https://www.nejm.org/doi/full/10.1056/NEJMoa2214131
2. https://ascopubs.org/doi/full/10.1200/JCO.21.01926
3. https://www.novartis.com/news/media-releases/sandoz-biologics-license-application-proposed-biosimilar-denosumab-accepted-us-fda
4. https://news.vrtx.com/news-releases/news-release-details/positive-results-pivotal-trials-exa-cel-transfusion-dependent
5. https://www.henlius.com/en/NewsDetails-4024-26.html
6. https://www.arcutis.com/arcutis-announces-fda-acceptance-of-new-drug-application-for-roflumilast-foam-0-3-for-the-treatment-of-seborrheic-dermatitis-in-individuals-aged-9-years-and-older/
7. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02034-7/fulltext
8. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2117175?articleTools=true
9. https://www.businesswire.com/news/home/20230629900551/en/Italfarmaco-Group-Completes-FDA-Submission-of-New-Drug-Application-for-Givinostat-in-Duchenne-Muscular-Dystrophy-and-Receives-Priority-Review
10. https://jamanetwork.com/journals/jama/article-abstract/2810248?resultClick=1
11. https://www.ophthalmologytimes.com/view/breaking-news-glaukos-announces-fda-acceptance-of-nda-submission-for-idose-tr
12. https://www.ganlee.com/detail/683.html
13. https://www.merck.com/news/mercks-gefapixant-45-mg-twice-daily-significantly-decreased-cough-frequency-compared-to-placebo-at-week-12-and-24-in-patients-with-refractory-or-unexplained-chronic-cough/