April 2024 decisions expected from the FDA

Your monthly synopsis of new drugs expected to hit the market

March 14, 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 United States (U.S.) Food and Drug Administration (FDA).

Drug pipeline for April 2024:

2Q2024: fidanacogene elaparvovec

Fidanacogene elaparvovec is a gene therapy by Pfizer that is awaiting FDA approval for the treatment of hemophilia B. It contains a bio-engineered adeno-associated virus (AAV) capsid and a high-activity variant of the human coagulation Factor IX (FIX) gene to enable patients with hemophilia B to produce adequate levels of FIX and to avoid bleeds without regular infusions of exogenous FIX. In the phase 3 BENEGENE-2 trial, fidanacogene elaparvovec was superior to prophylactic exogenous FIX in adult males with moderately severe to severe hemophilia B, reducing the annualized bleeding rate (ABR) by 71% during weeks 12 weeks to 15 months.¹ If approved, fidanacogene elaparvovec will be the second gene therapy for hemophilia B and will compete with Hemgenix® (etranacogene dezaparvovec-drlb). Both gene therapies deliver a FIX Padua transgene and are intended to be given as a single dose in a patient’s lifetime. Fidanacogene elaparvovec received Breakthrough Therapy, Orphan Drug and Regenerative Medicine Advanced Therapy designations.

For more information, see the fidanacogene elaparvovec Deep Dive in the January 2024 edition of the Quarterly Pipeline.

2Q2024: levodopa/carbidopa patch pump (ND0612)

Mitsubishi Tanabe submitted a 505(b)(2) new drug application (NDA) for ND0612, a device that delivers a continuous 24 hours/day subcutaneous (SC) infusion of liquid levodopa/carbidopa. ND0612 was submitted for the treatment of motor fluctuations in patients with Parkinson’s disease (PD). In the 12-week, double-blind, phase 3 BouNDless trial, ND0612 demonstrated a statistically significant increase by 1.72 hours (95% confidence interval [CI], 1.08 to 2.36; p<0.0001) in ON time without troublesome dyskinesia compared to oral immediate-release levodopa/carbidopa.² If approved, ND0612 will provide a non-surgical, drug-device option to control motor fluctuations in patients with PD. The medication is delivered subcutaneously using a pump system and has the potential for self-administration. Use of ND0612 is intended to overcome the challenges associated with oral levodopa/carbidopa, notably, its relatively narrow therapeutic window and low gastrointestinal absorption. However, the levodopa dose delivered by the pump may be limited and dosage increases may require oral add-on therapy.

04/01/2024: insulin lispro biosimilar

Gan & Lee is seeking FDA approval for their insulin lispro biosimilar candidate to Eli Lilly’s Humalog®, a rapid-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. If approved, it will be the first biosimilar for Humalog in the U.S. and will be commercialized by Sandoz. Other insulin lispro products currently available in the U.S. include Admelog® (insulin lispro U-100) by Sanofi-Aventis, which was approved under a 505(b)(2) NDA, and Lyumjev™ (insulin lispro-aabc U-100 and U-200) by Eli Lilly, approved under a 351(a) biologics license application (BLA).

04/03/2024: ceftobiprole (Zevtera®)

The FDA is reviewing the advanced generation intravenous (IV) cephalosporin antibiotic, ceftobiprole, for the treatment of Staphylococcus aureus bacteremia (SAB), including right-sided infective endocarditis, acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). In the double-blind, phase 3 ERADICATE trial, ceftobiprole was non-inferior to daptomycin based on overall treatment success rates of 69.8% and 68.7% with the agents, respectively, in patients with SAB.³ The double-blind, phase 3 TARGET trial reported that ceftobiprole was non-inferior to vancomycin plus aztreonam, with early clinical success rates of 91.3% and 88.1%, respectively, in patients with ABSSSI.4 Another double-blind, phase 3 trial (NCT00326287) demonstrated that ceftobiprole was non-inferior to ceftriaxone ± linezolid in patients with CABP, with reported cure rates of 86.6% and 87.4%, respectively.5 Ceftobiprole is a broad-spectrum IV antibiotic with activity against gram-positive and gram-negative bacteria, including methicillin-resistant S. aureus (MRSA). The agent was granted Qualified Infectious Disease Product designation by the FDA. If approved, it will provide another option in the infectious disease armamentarium, reducing the need for multiple antibiotics to treat mixed infections.

04/05/2024: apomorphine infusion device (SPN-830)

Supernus is awaiting FDA decision for SPN-830 for the continuous treatment of motor fluctuations (OFF episodes) in Parkinson’s disease (PD). The NDA was resubmitted following a Refusal to File (RTF) by the FDA in 2021 and a Complete Response Letter (CRL) in 2022, which required additional information for areas including labeling, product quality and manufacturing, device performance and risk analysis, but not additional safety and efficacy data. The European-based, double-blind, phase 3 TOLEDO trial reported a significantly greater reduction in mean daily OFF time with SPN-830 compared to placebo (2.47 versus 0.58 hours, respectively; p=0.0025) in patients with PD with motor fluctuations not optimally controlled by oral medication.6 Top-line results from the U.S.-based, open-label, phase 3 INFUS-ON trial reported a mean daily OFF time reduction from baseline to week 12 by 3 hours (p<0.0001).7 If approved, SPN-830 could compete with Mitsubishi Tanabe’s levodopa/carbidopa drug-device ND0612. Apomorphine is available as brand Apokyn®, as a caregiver or self-administered subcutaneous injection for acute, intermittent treatment of hypomobility, OFF episodes in patients with advanced PD.

04/14/2024: insulin aspart biosimilar

Gan & Lee is seeking FDA approval for their investigational insulin aspart biosimilar to Novo Nordisk’s Novolog®, a rapid-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. If approved, it will be the first biosimilar for Novolog approved in the U.S. and will be marketed by Sandoz.

04/16/2024: ustekinumab biosimilar (AVT04)

Alvotech is seeking FDA approval for AVT04, a biosimilar candidate to Janssen’s Stelara®, an interleukin (IL) 12/23 antagonist indicated for the treatment of plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis in select patients. If approved, AVT04 will be the second biosimilar for Stelara and will be marketed by Teva in the U.S. with launch anticipated in 2025.

04/21/2024: ranibizumab biosimilar

STADA and Xbrane are seeking FDA approval for their investigational ranibizumab biosimilar to Lucentis®, a vascular endothelial growth factor (VEGF) inhibitor for intravitreal injection that is indicated for the treatment of neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR) and myopic choroidal neovascularization (mCNV). If approved, it will be the third biosimilar for Lucentis available in the U.S.

04/23/2024: nogapendekin alfa inbakicept (N-803)

N-803 is a first-in-class interleukin 15 (IL-15) superagonist complex for intravesical administration. It is under review by the FDA for use in combination with Bacillus Calmette-Guérin (BCG) for the treatment of BCG-unresponsive, non-muscle-invasive bladder cancer (NMIBC) carcinoma in situ (CIS) with or without Ta or T1 papillary disease. N-803 was granted Breakthrough Therapy and Fast Track designations by the FDA. Interim analysis of the open-label, single-arm, QUILT-3.032 trial reported that treatment with N-803 plus BCG resulted in a complete response rate of 71% in patients with or without Ta/T1 papillary disease after a median follow-up of 23.69 months.8 Among patients who achieved a complete response, 89.2% avoided cystectomy. Up to 40% of patients with NMIBC will fail BCG therapy and are left with limited subsequent treatment options. Repeat intravesical chemotherapy (Valstar® [valrubicin]), the checkpoint inhibitor Keytruda® (pembrolizumab) or the gene therapy Adstiladrin® (nadofaragene firadenovec-vncg) may be considered in select patients (BCG-unresponsive, high-risk, NMIBC with CIS or high-grade Ta/T1). If approved, N-803 will offer a treatment with a new mechanism of action in the BCG-unresponsive NMIBC space.

04/24/2024: pivmecillinam

The FDA granted a Priority Review for Utility Therapeutics’ pivmecillinam for the treatment of uncomplicated urinary tract infection (uUTI). Pivmecillinam is an oral aminopenicillin with activity against gram-negative bacteria, including extended-spectrum beta-lactamases. It holds FDA’s Qualified Infectious Disease Product (QIDP) designation. Pivmecillinam has been used as a first-line option for treating uncomplicated cystitis in women outside the U.S.; additional first-line options are fosfomycin and nitrofurantoin.9

04/30/2024: mavorixafor

Mavorixafor by X4 Pharmaceuticals is undergoing a Priority Review for the treatment of a rare, inherited, primary immunodeficiency, known as WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, in patients aged 12 and older. The FDA granted the once-daily, oral chemokine receptor CXCR4 antagonist Breakthrough Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease (RPD) designations. The NDA submission is supported by data from the phase 3, double-blind 4WHIM trial that demonstrated a significant reduction by approximately 60% in annualized infection rate with mavorixafor compared to placebo (p<0.01) in patients with genotype-confirmed WHIM syndrome.10 In addition, total duration of infection was reduced by over 70% in patients treated with mavorixafor compared to those who received placebo in the 52-week trial (mean duration, 14.1 versus 49.1 days, respectively). If approved, mavorixafor will be the first agent approved for this rare condition.

04/30/2024: tovorafenib

Day One is awaiting approval for their oral, selective, type II RAF kinase inhibitor, tovorafenib, for the treatment of relapsed or progressive pediatric low-grade glioma (pLGG). The agent targets a key enzyme in the mitogen-activated protein kinase (MAPK) signaling pathway and displays potent activity against both oncogenic BRAF fusions and BRAF V600 mutation. The open-label, phase 2 FIREFLY-1 trial enrolled patients 6 months to 25 years of age with recurrent or progressive pLGG.¹¹ In the study, once weekly oral doses of tovorafenib led to an overall response rate of 67% (primary endpoint), with a complete response rate of 17% and a median duration of response of 16.6 months. Most cases of pLGG harbor a BRAF gene mutation (e.g., BRAF-KIAA1549 translocation, BRAF V600E mutation), which is unique to pLGG. Treatment with tovorafenib, a type II RAF kinase inhibitor, has been shown to be effective in patients with pLGG and appears unlikely to induce paradoxical activation of the MAPK pathway. Activation of this pathway can promote accelerated tumor growth and is associated with the type I RAF inhibitor, Tafinlar® (dabrafenib),  which is used in combination with Mekinist® (trametinib) as first-line treatment of pLGG with BRAF V600E mutation. If approved, tovorafenib may provide an new treatment option in select patients with pLGG.

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