Multiple new medications for a variety of medical conditions were given the go light by the FDA in 2024. New medications with a wide range of indications have been brought to the pipeline this year, including cancer, infectious illnesses, genetic disorders, and uncommon diseases. A number of uncommon illnesses and malignancies are now the focus of research into promising new cellular and gene treatments.
Donanemab (approved by FDA in July 2024): In July 2024, the FDA authorized Donanemab, a humanized IgG1 antibody that targets an N-terminal pyroglutamate Aβ epitope seen only in existing plaques. The compound only binds to this particular epitope, does not attach to other Aβ species, neurotransmitters, or their receptors, and it does not cause any known side effects. After numerous doses of donanemab were administered, the safety, pharmacokinetics, and pharmacodynamics were evaluated in a phase 1a research comprising patients with amyloid-positive prodromal-to-moderate Alzheimer’s disease. At 76 weeks, donanizumab outperformed placebo in individuals with early-stage Alzheimer’s disease (n=257) on a composite measure of cognition and ADL performance.
Deuruxolitinib (approved by FDA in July 2024): It is a selective Janus kinase inhibitor for JAK1 and JAK2. A substantial percentage of adult patients with alopecia areata and ≥50% scalp hair loss experienced ≤20% scalp hair loss after 24 weeks of treatment with deuruxolitinib compared to placebo. Enhancements in hair growth were seen in patient satisfaction ratings regarding hair. Deuruxolitinib demonstrated good tolerability and efficacy; however, extended investigations are necessary.
Vorasidenib (approved by FDA in August 2024): In gliomas with an IDH mutation, the oral brain-penetrant inhibitor vorasidenib shown some efficacy. Out of a total of 331 patients, 168 were given vorasidenib and 163 were given a placebo. Among 226 patients, or 68.3%, who were still on vorasidenib or placebo at the median follow-up of 14.2 months, the treatment was being maintained. Median progression-free survival was 27.7 months in the vorasidenib group and 11.1 months in the placebo group; hazard ratio for disease progression or death was 0.39 (95% CI, 0.27 to 0.56; P<0.001). It was also shown that progression-free survival was considerably enhanced in the vorasidenib group. Compared to the placebo group, the vorasidenib group had a substantially longer duration until the next intervention.
Palopegteriparatide (approved by FDA in August 2024): The estimated glomerular filtration rate (eGFR), a metric for kidney function, showed substantial improvements after 52 weeks of palopegteriparatide treatment. More than 57% of individuals deemed improvements in estimated glomerular filtration rate (eGFR) from baseline to week 52 as clinically significant. Even more impressive were the eGFR improvements in the 74% of patients who had pre-trial poor kidney function; these changes were clinically significant. Treatment with palopegteriparatide may improve kidney function in adults suffering from chronic hypoparathyroidism, according to these findings. This is particularly true for individuals with compromised kidney function.
Nemolizumab (approved by FDA in August 2024): Nemolizumab is a humanized monoclonal antibody injected subcutaneously that targets interleukin-31 receptor A, implicated in itch and inflammation associated with atopic dermatitis. In this 16-week trial, the administration of subcutaneous nemolizumab alongside topical medications for atopic dermatitis yielded a more significant reduction in pruritus compared to placebo with topical treatments. The frequency of injection-site responses was higher with nemolizumab compared to placebo.
Axatilimab (approved by FDA in August 2024): The humanized IgG4 monoclonal antibody axatilimab has a high affinity (KD 4-8 pM) for the ligand-binding region on CSF-1R and has bound to known variations of CSF-1R (V32G, A245S, P247H, and V279M). Without antibody-mediated receptor internalization or activation, axilimab limits binding of both CSF-1 and interleukin-34 ligands and strongly reduces ligand-induced monocyte activation (IC50 100-400 pM). Axatilimab showed a selective removal of nonclassical monocytes from peripheral blood and a safety profile that was in line with its action mechanism in early-phase clinical trials.
Seladelpar (approved by FDA in August 2024): Seladelpar is a powerful, selective agonist of the peroxisome proliferator-activated receptor-delta (PPAR-δ), which plays a role in bile acid homeostasis. Seladelpar normalized alkaline phosphatase levels in individuals who underwent 12 weeks of treatment.
Lazertinib (approved by FDA in August 2024): For the treatment of non-small cell lung cancer (NSCLC), Yuhan and Janssen Biotech are developing Lazertinib, an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The T790M mutation, activating EGFR mutations Ex19del and L858R, and wild type-EGFR are all spared by this brain-penetrant, irreversible EGFR-TKI. In patients whose NSCLC progressed during or after EGFR TKI treatment, lazertinib demonstrated promoting clinical activity and had an acceptable safety profile.
Lebrikizumab (approved by FDA in September 2024): The development of the interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex is prevented by lebrikizumab, a high-affinity IgG4 monoclonal antibody that targets interleukin-13. Lebrikizumab, when administered for 16 weeks, effectively treated moderate-to-severe atopic dermatitis in both adults and adolescents during the induction periods of two phase 3 trials.
Arimoclomol (approved by FDA in September 2024): Cerebrospinal fluid from amyotrophic lateral sclerosis patients who have taken the small drug arimotrol has shown that it passes the blood-brain barrier. Not only does arimotrolol directly facilitate lysosomal activity, but it also increases the body’s natural reaction to cellular stress by triggering the heat shock response (HSR) and producing heat shock proteins (HSPs) to avoid protein misfolding. As a result, arimoclomol guards against lysosomal stress-induced cell death while maintaining cellular function.Despite its side effects, arimodoclomol was well-tolerated and effectively treated Niemann-Pick disease type C (NPC).
Levacetylleucine (approved by FDA in September 2024): Levacetylleucine is an oral medicine utilized for the management of neurological symptoms associated with Niemann-Pick disease type C. Levacetylleucine is a derivative of the amino acid leucine (N-Acetyl-L-Leucine). Levacetylleucine is approved for the management of neurological signs of Niemann-Pick disease type C in individuals weighing a minimum of 15 kilograms (33 lb).
Xanomeline and trospium chloride (approved by FDA in September 2024): Xanomeline is a dual agonist for M1 and M4 muscarinic receptors, exhibiting no direct antagonistic effect on D2 dopamine receptors. KarXT integrates xanomeline with the peripheral muscarinic receptor antagonist trospium chloride to mitigate deleterious effects associated with xanomeline-induced peripheral muscarinic receptor activation. Previous trials shown that xanomeline-trospium chloride effectively alleviated psychotic symptoms and was generally well tolerated by individuals with schizophrenia.
Flurpiridaz F 18(approved by FDA in September 2024): Flurpiridaz F-18 is an innovative tracer for positron emission tomography (PET) myocardial perfusion imaging. Flurpiridaz F 18 has demonstrated attributes of an almost optimal MPI tracer in pre-clinical and phase I investigations. In the phase 2 experiment, PET MPI with flurpiridaz F 18 demonstrated safety and superiority over SPECT MPI in terms of picture quality, interpretive certainty, and total coronary artery disease diagnosis.
Ceftobiprole medocaril sodium (approved by FDA in April 2024): Ceftobiprole medocaril sodium is a fifth-generation cephalosporin authorized in Europe for monotherapy in the treatment of hospital-acquired pneumonia (HAP), except ventilator-associated pneumonia (VAP). It is swiftly transformed into the active metabolite ceftobiprole after intravenous injection. Ceftobiprole exhibits a wide range of efficacy, particularly against methicillin-resistant Staphylococcus aureus, ampicillin-susceptible enterococci, penicillin-resistant pneumococci, and Enterobacteriaceae that do not produce extended-spectrum β-lactamase. Ceftobiprole is predominantly eliminated by renal glomerular filtration, with a limited tendency for interactions with concurrently given medications. The standard dosage of ceftobiprole is 500 mg, delivered via a 2-hour intravenous infusion every 8 hours, with dosage modification based on renal function. In a crucial Phase III trial including patients with hospital-acquired pneumonia (HAP), ceftobiprole monotherapy shown equivalent efficacy to ceftazidime/linezolid for both clinical and microbiological cure, and was noninferior to ceftazidime/linezolid in the subset of patients with HAP excluding ventilator-associated pneumonia (VAP). Ceftobiprole and ceftazidime/linezolid had comparable tolerability. Ceftobiprole is an effective and well-tolerated choice for the empirical treatment of patients with hospital-acquired pneumonia (excluding ventilator-associated pneumonia).
Pegulicianine (approved by FDA in April 2024): Pegulicianine is an optical imaging agent approved for fluorescence imaging in individuals with breast cancer. It is utilized post-surgical excision of the original neoplasm to identify regions of residual malignancy. Pegulicianine is a prodrug composed of three primary pieces, one of which includes a fluorescence quencher that renders the parent molecule optically inactive. The in vivo enzymatic cleavage of pegulicianine produces two optically active fragments that provide a detectable fluorescent signal using a fluorescence imaging equipment.
Nogapendekin alfa inbakicept (approved by FDA in April 2024): Nogapendekin alfa inbakicept is a recombinant interleukin-15 (IL-15) superagonist protein complex designed for the treatment of solid tumors, hematological malignancies, and HIV infection. It functions synergistically with Bacillus Calmette-Guérin (BCG) to induce sustained complete responses (CRs) in this patient demographic.
Tovorafenib (approved by FDA in April 2024): Day One Biopharmaceuticals, Inc. is developing tovorafenib, a selective type II RAF kinase inhibitor that is brain-penetrant and administered once weekly orally, for the treatment of solid tumors and pediatric low-grade glioma (pLGG). This drug is licensed from Takeda Oncology. The majority of pLGGs have abnormal intracellular signaling because to changes in the MAPK pathway, including a BRAF mutation or BRAF fusion. Mutant BRAF V600E, wild-type BRAF, and wild-type CRAF kinases, as well as BRAF fusions, are all inhibited by tovorafenib. Tovorafenib was initially authorized in the United States in April 2024 for the treatment of patients who were at least 6 months old and had pLGGs that had relapsed or were resistant, as long as they had a BRAF fusion, rearrangement, or V600 mutation. Ongoing pivotal phase 2 FIREFLY-1 research results regarding response rate and duration of response in this cohort led to expedited approval for this indication.
Mavorixafor (approved by FDA in April 2024): Mavorixafor is an orally administered, selective antagonist of C-X-C chemokine receptor 4 (CXCR4). It prevents the binding of CXCR4 to stromal derived factor-1, another name for CXCR4. This therapy was approved for the first time in April 2024 in the United States for WHIM syndrome, an acronym for Warts, Hypogammaglobulinaemia, Infections, and Myelokathexis. It is indicated for use in patients aged 12 years and older with WHIM syndrome to boost the quantity of mature neutrophils and lymphocytes in the blood.
Tarlatamab (approved by FDA in May 2024): To treat neuroendocrine prostate cancer and small cell lung cancer (SCLC), tarlatamab is a first-in-class bispecific CD3 T-cell engager driven by delta-like ligand 3 (DLL3). When tarlatamab attaches to both tumor cell surface DLL3 and cytotoxic T lymphocyte (CTL) surface CD3, it triggers the activation of T cells, the secretion of inflammatory cytokines, and the killing of tumor cells expressing DLL3 through the mediation of CTLs. Adults with ES-SCLC who have cancer progression during or after platinum-based chemotherapy were the first to get tarlatamab’s US clearance in May 2024. The data from the pivotal phase 2 DeLLphi-301 study, which measured the overall response rate and duration of response, led to expedited approval for this indication for tarlatamab. The drug’s ongoing approval might hinge on the results of confirmatory trials showing therapeutic benefit.
Imetelstat (approved by FDA in June 2024): Imetelstat is a 13-mer oligonucleotide that is complementary to the template region of the telomerase RNA component. It exhibits high-affinity binding to the template region of the RNA component of telomerase, leading to direct, competitive suppression of telomerase enzymatic activity. Preclinical investigations have demonstrated that imetelstat suppresses telomerase activity and cell growth in several cancer cell lines and human tumors within mice xenograft models. Furthermore, imetelstat suppresses the growth and promotes death of cancer stem cells.
Elafibranor (approved by FDA in June 2024): The first-in-class PPAR agonist elafibranor is used to treat PBC and PSC, which are primary biliary cholangitis and primary sclerosing cholangitis, respectively. For the treatment of PBC in adults with an unsatisfactory response to ursodeoxycholic acid (UDCA) or as monotherapy in those unable to tolerate UDCA, elafibranor was expeditedly approved on 10 June 2024 in the USA based on decrease of alkaline phosphatase (ALP).
Sofpironium (approved by FDA in June 2024): For hyperhidrosis, a topical anticholinergic medication called sofpironium bromide gel can be used. To lessen perspiration, the medicine blocks eccrine gland M3 muscarinic receptors where the medication is applied. Primarily approved for the treatment of primary axillary hyperhidrosis (PAH) in Japan in September 2020 was sofpironium bromide gel 5%.
Crovalimab (approved by FDA in June 2024): Crovalimab is a humanized monoclonal antibody targeting complement component C5, currently under investigation for the treatment of complement-mediated disorders such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, lupus nephritis, and sickle cell disease. Crovalimab inhibits the cleavage of C5 into C5a and C5b, hence obstructing the terminal complement pathway and averting intravascular hemolysis in PNH. Crovalimab is engineered to attach to the antigen persistently, facilitating prolonged complement inhibition at reduced dosages and enabling monthly subcutaneous injection.
Ensifentrine (approved by FDA in June 2024): To treat respiratory illnesses, such as chronic obstructive pulmonary disease (COPD), ensifentrine is breathed and acts as a selective phosphodiesterase (PDE) 3 and PDE4 inhibitor. Maintenance therapy of chronic obstructive pulmonary disease (COPD) in adults in the United States was authorized for ensifentrine inhalation suspension in June 2024.
Berdazimer (approved by FDA in January 2024): For the treatment of molluscum contagiosum (MC), there is a topical gel called Berdazimer that releases nitric oxide (NO). The concentration of this gel is 10.3%. The creators of berdazimer topical gel, Novan, utilized their in-house NO-based technological platform to create a 10.3% solution. This platform stores gaseous NO species on big polymers. For the topical treatment of MC in adults and children aged 1 and up, the US Food and Drug Administration authorized berdazimer topical gel, with a concentration of 10.3%, in January 2024.
Cefepime and enmetazobactam (approved by FDA in February 2024): For the treatment of infections caused by Gram-negative bacteria that are multi-drug-resistant (MDR), the intravenous (IV) antibacterial fixed-dose combination of cefepime and enmetazobactam is utilized. Adults suffering from pyelonephritis and other complicated urinary tract infections (cUTIs) caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex were given the green light to use cefepime/enmetazobactam in February 2024 by the US Food and Drug Administration.
LetibotulinumtoxinA (approved by FDA in February 2024): LetibotulinumtoxinA is a complex of botulinum toxin type A (BoNT-A) that originates from the Clostridium botulinum strain CBFC26 and has a molecular weight of 900 kDa. It causes flaccid paralysis by blocking the neuromuscular junction’s axon terminals from releasing the neurotransmitter acetylcholine. It wasn’t until February 2024 that it received FDA approval for medicinal usage. In Weeks 1, 2, and 4, the response rates to letibotulinumtoxinA were much greater in females aged 35 to 50 compared to other female patients. From Week 15 to Week 16, response rates stayed elevated. Vertical glabellar lines were successfully and safely treated in this cohort of patients.
Tislelizumab (approved by FDA in March 2024): An immunotherapeutic medication targeted against neoplasms, tislelizumab is an IgG4 monoclonal antibody that fights against human programmed death receptor-1 (PD-1). In December 2019, tislelizumab was approved in China for patients with relapsed or refractory classical Hodgkin’s lymphoma following at least second-line chemotherapy, based on its investigation in haematological malignancies and advanced solid tumors.In the United States, tislelizumab is prescribed to people who have esophageal squamous cell carcinoma that has spread or cannot be removed by surgery, and who have previously had systemic chemotherapy without a PD-(L)1 inhibitor.
Resmetirom (approved by FDA in March 2024): The oral thyroid hormone receptor-β (THR-β) agonist Resmetirom is currently under development with the aim of addressing the fundamental causes of metabolic dysfunction associated steatohepatitis (MASH) (formerly known as nonalcoholic steatohepatitis, NASH). The United States Food and Drug Administration (FDA) authorized resmetirom for the treatment of people with noncirrhotic nonalcoholic steatohepatitis (NASH) who have moderate to advanced liver fibrosis (corresponding to stages F2 to F3) in March 2024, with the addition of dietary and physical activity recommendations.
Aprocitentan (approved by FDA in March 2024): For hypertension, aprocitentan is an oral drug that blocks the receptors for endothelin A (ETA) and endothelin B (ETB). Hypertension has been linked to the endothelin pathway. Aprocitentan reduces blood pressure via blocking endothelin-1’s binding to the ETA and ETB receptors, which ends the drug’s harmful effects. The first American clearance for aprocitentan came in March 2024, and it is used to treat hypertension in individuals whose blood pressure is not sufficiently controlled with existing antihypertensive medications.
Givinostat (approved by FDA in March 2024): The oral histone deacetylase inhibitor givinostat is used to treat polycythemia vera and muscular dystrophy. For the treatment of Duchenne muscular dystrophy (DMD) in individuals aged 6 and above, Givinostat was initially approved in the USA on March 21, 2024. The global phase III EPIDYS study provided the data that led to approval. Those who received givinostat demonstrated slower reduction in functional task time compared to those who received placebo. Patients with Duchenne muscular dystrophy (DMD) can now utilize givinostat, the first nonsteroidal therapy for the condition, regardless of the particular genetic mutation that causes it. Two times a day with meals, take an oral suspension of givinostat. The dose that is prescribed to a patient is determined by their weight.
Sotatercept (approved by FDA in March 2024): Sotatercept is an inhibitor of activin signaling, currently in development for the treatment of pulmonary arterial hypertension. Sotatercept has just been approved in the United States for the treatment of people with pulmonary arterial hypertension (WHO Group 1) to enhance exercise capacity, improve WHO functional classification, and diminish the likelihood of clinical deterioration episodes.
Vadadustat (approved by FDA in March 2024): Vadadustat is a prolyl hydroxylase inhibitor utilized for the management of anemia related to chronic kidney disease (CKD). Vadadustat can effectively enhance hemoglobin levels and facilitate iron use in chronic kidney disease patients with anemia without elevating the occurrence of severe side effects.
Danicopan (approved by FDA in March 2024): Danicopan is an oral complement factor D inhibitor under development as an adjunct therapy to ravulizumab or eculizumab for patients experiencing clinically severe extravascular hemolysis. Danicopan has just been approved in Japan for the treatment of individuals with paroxysmal nocturnal hemoglobinuria (PNH) as an adjunct to a complement component 5 (C5) inhibitor. It demonstrated efficacy and safety in PNH patients as monotherapy in a phase II study.
References
- Rim M H., et al., Recent and anticipated novel drug approvals for 2024, American Journal of Health-System Pharmacy, 2024, 81(10): 385-389.
- Verdin P. FDA new drug approvals in Q3 2024, Nature reviews drug discovery, 2024.
- Verdin P. FDA new drug approvals in Q2 2024, Nature reviews drug discovery, 2024.
- Verdin P. FDA new drug approvals in Q1 2024, Nature reviews drug discovery, 2024.