At Prime Therapeutics (Prime), we have positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs awaiting approval by the United States (U.S.) Food and Drug Administration (FDA).
 

Drug pipeline for October 2024

October-November 2024: ustekinumab biosimilar (DMB-3115)

Dong-A Socio and Meiji Seika are seeking FDA approval for DMB-3115 as a biosimilar to Janssen’s Stelara. Stelara is a human interleukin-12 and -23 antagonist that can be administered by subcutaneous (SC) injection or intravenous (IV) infusion and carries indications for plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis. If approved, DMB-3115 will be the fourth biosimilar to Stelara. Accord BioPharma commercialize DMB-3115 in the U.S.
 

October-December 2024: garadacimab

CSL Limited is awaiting FDA approval of garadacimab for prophylactic treatment of hereditary angioedema (HAE). The first-in-class recombinant monoclonal antibody that targets activated factor XII (FXII) was granted Fast Track and Orphan Drug to designations by the FDA. If approved, it will be available for once-monthly subcutaneous (SC) injection that the patient can self-administer. In the double-blind, parallel-group VANGUARD trial, garadacimab use resulted in a significant decrease in the primary efficacy endpoint of mean number of investigator-confirmed HAE attacks per month compared to placebo (0.27 versus 2.01, respectively; p<0·0001).1 No increase in the risk of bleeding or thromboembolic events was observed.

For more information, see the garadacimab Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline - Prime Therapeutics LLC
 

October-December 2024: marstacimab

Pfizer’s anti-tissue factor pathway inhibitor (anti-TFPI) marstacimab is under review by the FDA for the treatment of individuals with hemophilia A or hemophilia B without inhibitors to factor VIII (FVIII) or factor IX (FIX). The FDA has granted Fast Track and Orphan Drug designations. In the BASIS trial, over 12 months, marstacimab led to a 35.2% mean reduction (95% CI: 5.6-55.6; p=0.0376) in annualized bleeding rate (ABR) compared to routine prophylaxis and a 91.6%  reduction compared to on-demand intravenous (IV) treatment with factor VIII (FVIII) or factor IX (FIX) that was part of a 6-month observational period.2 If approved, it will be the first anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody to treat hemophilia. Patients will be able to self-administer the required once-weekly SC injection using an auto-injector. Notably, Novo Nordisk resubmitted their anti-TFPI monoclonal antibody concizumab for the treatment of hemophilia A or B with inhibitors and also submitted for the treatment of hemophilia A or B without inhibitors. FDA decisions are expected by the end of 2024 and in May 2025, respectively.
 

Oct. 21, 2024: octreotide SC depot  

Camurus’s octreotide SC depot is a ready-to-use, once-monthly octreotide formulation for SC self-administration under FDA review for the treatment of acromegaly. This reformulation of octreotide has demonstrated approximately a five-fold higher bioavailability compared to intramuscular (IM) octreotide long-acting release (LAR). The application for octreotide SC depot is supported by the 24-week, double-blind, phase 3 ACROINNOVA 1 study that enrolled adults who were on a stable dose of standard of care (SOC), octreotide LAR or lanreotide autogel, and were randomly switched to octreotide SC depot or placebo.3 The trial reported a significantly higher proportion of patients who received octreotide SC depot achieved a mean insulin-like growth factor-1 (IGF-1) level at or below the upper-limit of normal (ULN) range at weeks 22 and 24 (primary endpoint) compared to patients who were given placebo (72.2% versus 37.5%, respectively; p≤0.0018). Patients who received octreotide SC depot also reported a significant improvement in quality of life (QOL), in both the physical and psychological domains, compared to baseline. The 52-week, open-label, phase 3 ACROINNOVA 2 study included patients who were uncontrolled on SOC as well as patients who were rolled-over from the ACROINNOVA 1 trial.4 It reported significant increases in treatment response rates with octreotide SC depot of 12.7% in the overall population, and 22.8% in new patients compared to SOC at baseline. Among roll-over patients, biochemical control was maintained or regained (in patients switched from placebo) with octreotide SC depot. If approved, octreotide SC depot may provide a more convenient method of administering injectable octreotide compared to currently available health care professional-administrated monthly IM injections that require reconstitution or refrigeration. If approved, octreotide SC depot will be the second, self-administered treatment for acromegaly, following oral delayed-release octreotide (Mycapssa).
 

Oct. 25, 2024: sulopenem etzadroxil/probenecid (oral sulopenem)

Iterum has resubmitted sulopenem etzadroxil/probenecid to the FDA for the treatment of uncomplicated urinary tract infections (uUTIs) in adult women. The oral medication was granted Fast Track and Qualified Infectious Disease Product (QIDP) designations. This is the second review of the product, after the FDA issued a complete response letter (CRL) in 2021 requesting additional clinical data. Sulopenem has potent in vitro activity against a range of gram-negative, gram-positive and anaerobic bacteria that are resistant to other antibiotics. In the double-blind, phase 3 SURE-1 trial, oral sulopenem was superior to oral ciprofloxacin in quinolone-resistant women with uUTI, based on overall end of treatment (EOT) response (64.6% versus 30.2%), overall test-of-cure (TOC) response (62.6% versus 36%), and clinical TOC response (83% versus 62.6%) (p<0.001 for all).5 However, higher response rates with oral sulopenem compared to ciprofloxacin were not observed among quinolone-susceptible patients. Oral sulopenem was also evaluated in the double-blind, phase 3, REASSURE trial and was found to be superior to amoxicillin/clavulanate (Augmentin) based on the primary endpoint of clinical and microbiologic response at the TOC in women with uUTI with an amoxicillin/clavulanate-susceptible organism.6 In clinical trials, oral sulopenem was dosed twice daily for five days. If approved, it will be the first oral penem antibiotic available in the U.S.
 

Oct. 30, 2024: treosulfan

Medexus is awaiting FDA decision of treosulfan for use in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in adult and pediatric patients. This is the second review by the FDA for the orphan drug, after the FDA issued a CRL in 2021 requiring additional clinical information and a refusal to file letter in 2022. An open-label, phase 3 trial (NCT00822393) conducted at European sites reported that treosulfan was superior to reduced-intensity conditioning (RIC) busulfan when either were combined with fludarabine as a conditioning regimen for allogeneic HSCT for older or comorbid patients with acute myeloid leukemia or myelodysplastic syndrome.7 The primary endpoint of event-free survival (with disease recurrence, graft failure, or death from any cause as events) 36 months after HSCT was 59.5% with treosulfan and 49.7% with RIC busulfan (p=0.0000001 for non-inferiority, p=0.0005787 for superiority). The incidence of treatment-related adverse events (all grades) was similar between the groups. If approved, treosulfan could be an important option in patients undergoing allogeneic HSCT, particularly those who are older or with comorbid conditions that puts them at risk for excess regimen-related morbidity and mortality.