February 2024 decisions expected from the FDA

January 12, 2024

Your monthly synopsis of new drugs expected to hit the market

FDA Decisions Expected

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 February 2024:

February 2024: ABP-959 (eculizumab)

The United States (U.S.) Food and Drug Administration (FDA) is reviewing Amgen’s application for ABP-959, a proposed biosimilar to Alexion’s complement inhibitor Soliris® (eculizumab). Soliris carries indications in select patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). The double-blind, active-controlled, crossover DAHLIA study demonstrated similar efficacy (based on the control of intravascular hemolysis as measured by lactate dehydrogenase [LDH]), safety and immunogenicity between ABP-959 and Soliris in adults with PNH.¹ If approved, ABP-959 will be the first biosimilar available for Soliris in the U.S.

February 2024: TAK-721 (budesonide oral suspension)

The FDA is reviewing the 505(b)(2) new drug application (NDA) for TAK-721, by Takeda, for the short-term treatment of eosinophilic esophagitis (EoE). TAK-721 is a muco-adherent topically active viscous formulation. The double-blind, phase 3 ORBIT-1 trial enrolled patients 11 to 55 years of age with EoE and dysphagia and reported that twice daily doses of TAK-721 led to a significant increase the rate of histologic response (≤ 6 eosinophils/high-powered field) compared to placebo (53.1% versus 1%, respectively; p<0.001) after 12 weeks.² The trial also reported a significant difference in the proportion of patients who experienced at least a 30% reduction in dysphagia between the two groups (52.6% versus 39.1%, respectively; p=0.024). Oral and esophageal candidiasis were reported in < 5% of patients in either group. A separate withdrawal study, which included patients from ORBIT-1, reported higher rates of relapses in histologic and dysphagia symptoms over 36 weeks among patients who stopped TAK-721 compared to those who continued TAK-721 treatment (histologic, 43.5% versus 24% [p=0.131]; dysphagia, 50% versus 16.7% [p=0.038], respectively).³ The FDA has granted TAK-721 Breakthrough Therapy and Orphan Drug designations for EoE. If approved, TAK-721 will be the first corticosteroid indicated for EoE in the U.S.

02/22/2024: cefepime/taniborbactam

Venatorx Pharmaceutical’s intravenously (IV)-administered beta-lactam/beta-lactamase inhibitor antibiotic, cefepime/taniborbactam, is undergoing a review by the FDA for the treatment of adults with complicated urinary tract infections (cUTI), including pyelonephritis. Cefepime/taniborbactam was granted Priority Review as well as Fast Track and Qualified Infectious Disease Product (QIDP) designations. The combination product demonstrated in vitro activity against carbapenem-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa and extended spectrum beta-lactamase (ESBL)-producing Enterobacterales. The double-blind, phase 3, CERTAIN-1 study demonstrated that cefepime/taniborbactam was superior to meropenem in adults with cUTI, including acute pyelonephritis, based on the primary efficacy endpoint of composite microbiologic and clinical success at the Test of Cure (TOC) visit (day 19-23), which occurred in 70.6% of patients treated with cefepime/taniborbactam and 58% in those treated with meropenem (p=0.0088 for superiority).4 Cefepime/taniborbactam displays a broad spectrum of in-vitro activity against carbapenem resistance, and if approved, may provide an option in patients with antimicrobial resistant bacterial infections.

02/24/2024: AVT02 (adalimumab)

The FDA is reviewing Alvotech’s tumor necrosis factor (TNF) inhibitor, AVT02, as a high-concentration, interchangeable biosimilar candidate to Abbvie’s Humira® (adalimmab). Humira carries indications for rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), plaque psoriasis (PSO), psoriatic arthritis (PsA),Crohn’s disease (CD), Ulcerative colitis (UC), hidradenitis suppurativa (HS), and uveitis. A double-blind, three-arm, parallel study, demonstrated similar pharmacokinetics, safety, tolerability, and immunogenicity between AVT02, and U.S. and European versions of Humira (primary endpoint) when given as a single 40 mg subcutaneous dose in healthy adults.5 Alvotech received three prior complete response letters (CRLs) for AVT02 due to manufacturing site deficiencies. If approved, AVT02 will be the first interchangeable, high-concentration biosimilar to Humira in the U.S.

02/24/2024: lifileucel

Iovance is awaiting FDA approval of lifileucel, an autologous tumor infiltrating lymphocyte (TIL) therapy, to treat advanced unresectable or metastatic melanoma that has progressed after anti-programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy and targeted therapy. Lifileucel is administered as a single IV infusion. Data from Cohorts 2 and 4 from a single-arm, open-label, phase 2 trial (C-144-01; NCT02360579) were reported for 153 patients who received lifileucel. In the trial, patients also received preconditioning lymphodepleting therapy, and the lifileucel infusion was followed by interleukin-2 (IL-2) administration.6,7 At a median follow-up of 48.1 months, the objective response rate (primary endpoint) was 31.4%, and 54.2%, 39.6%, 33.3%, and 20.8% of responses lasted ≥ 12, ≥ 24, ≥ 36, and ≥ 48 months, respectively. The median overall survival (OS) was 13.9 months; OS rates were 54%, 33.9%, 28.3%, and 22.2%, at the 1-, 2-, 3-, and 4-year timepoints, respectively. Treatment-related adverse events were consistent with lymphodepleting and IL-2 therapy. If approved, lifileucel will be the only TIL therapy for patients with advanced or metastatic melanoma and the first one-time cell therapy to treat a solid tumor. Lifileucel was granted a Priority Review, as well as Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy designations by the FDA. Iovance is also seeking Accelerated Approval of lifileucel for patients with advanced melanoma.

02/26/2024: roluperidone

The FDA is reviewing the NDA for oral roluperiodone, by Minerva Neuroscience, for the treatment of negative symptoms associated with schizophrenia. Negative symptoms include a lack of motivation, speech, and ability to experience joy or pleasure, and cause patients with schizophrenia to withdraw from society. Roluperiodone is designed to block serotonin 2A (5-HT2A), sigma2 and α1A-adrenergic receptors that play a role in mood, cognition, sleep, and anxiety. Unlike first- and second-generation antipsychotics, roluperidone does not block dopaminergic receptors. Published data for a phase 3 (NCT03397134) trial, reported lower scores (improvement) for the primary endpoint of PANSS-derived Negative Symptom Factor Score (NSFS) with roluperidone 64 mg per day compared to placebo; this endpoint missed statistical significance for the intent-to-treat (ITT) analysis (p≤0.064) which was the primary endpoint. It reached nominal significance (p≤0.044) for the modified-ITT analysis.8 The FDA issued a Refuse to File letter in October 2022, Minerva then requested a Formal Dispute Resolution and appeal of the letter which led to the FDA reviewing the NDA for roluperidone.

02/27/2024: Exblifep® (cefepime/enmetazobactam)

Exblifep is an investigational IV antibiotic combination by Allecra under review by the FDA for the treatment of cUTIs. Exblifeb, a combination of a fourth generation cephalosporin and a beta lactamase inhibitor, has demonstrated activity against gram negative pathogens that exhibit ESBLs. Production of ESBLs is a key mechanism that pathogens use to evade antimicrobial therapy. The double-blind, phase 3 ALLIUM trial compared Exblifep and off-label IV piperacillin/tazobactam in patients with cUTI or acute pyelonephritis caused by gram-negative pathogens.9 Exblifeb demonstrated superiority over piperacillin/tazobactam based on the proportion of patients with cUTI achieving the primary composite endpoint of clinical cure (symptoms resolution) and microbiological eradication (<103 CFU/mL in urine culture) (79.1%  versus 58.9%, respectively; adjusted stratified difference, 21.2% [two-sided 95% confidence interval [CI], 14.3% to 27.9%; meeting the 10% non-inferiority margin with superiority). In addition, 20.9% of patients in the study had an ESBL-producing pathogen at baseline, of whom 73.7% and 51.5% treated with Exblifep or piperacillin/tazobactam, respectively, achieved the composite endpoint (difference 30.2%; 95% CI, 13.4% to 45.1%). Exblifep was well-tolerated. If approved, it will provide another option for the treatment of cUTI caused by gram negative pathogens, including organisms that produce ESBL. Other IV antibiotics with activity against ESBL-producing organisms include Fetroja® (cefiderocol), Avycaz® (ceftazidime/avibactam), Recarbrio™ (relebactam/imipenem/cilastatin), Vabomere® (meropenem/vaborbactam), and Zerbaxa® (ceftolozane/tazobactam). Exblifep was granted Fast Track and QIPD designation by the FDA, which could allow for a Priority Review by the Agency.

Related news


April 19, 2024

AMCP 2024: Behind the Research with Prerak Parikh

Parikh, director of medical pharmacy strategy at Prime/MRx, shares the latest on interchangeable biosimilars


April 19, 2024

LISTEN NOW: Live at AMCP Annual 2024 – Digging into managed care pharmacy insights | Pharmacy Friends podcast

In this episode, Prime/MRx clinicians — along with special guests — discuss the hottest topics covered at the Academy of Managed Care Pharmacy (AMCP)'s 2024 Annual Meeting in New Orleans


April 17, 2024

AMCP 2024: Behind the research with YuQian Liu

Ahead of her session with Andy Killpack, Liu — senior director of specialty clinical solutions at Prime/MRx — shares current care management strategies for cell and gene therapy and the future of this exciting frontier