EXPERT OPINION ON INVESTIGATIONAL DRUGS

Promising selective progesterone receptor modulators: what's new in female contraception?
Nelson A and Shapiro MP
Selective progesterone receptor modulators (SPRMs), such as mifepristone and ulipristal acetate (UPA), have demonstrated high efficacy and safety as single-dose treatments for medication abortion and emergency contraception (EC). Other obstetrical and gynecologic applications have emerged, both for episodic and ongoing uses. The potential of these compounds to provide estrogen-free, ongoing contraception is promising; however, the rare, but serious, hepatic injury cases seen with UPA have put at least a temporary halt to further research in this area.
The first-in-human study of QHRD106 functioning as a safe and effective long-acting kallikrein drug potentially aiding ischemic stroke
Huang L, Sun R, Song H, Chen Z, Hong Y, Yang H, Zhang Y, Wei L, Fei F and Li J
This study assessed the pharmacokinetics (PK), pharmacodynamics (PD) and safety of QHRD106, and made a comparison with urinary kallindinogenase (UKN) in healthy volunteers.
Progress in the clinical development of investigational systemic agents for recurrent and metastatic nasopharyngeal carcinoma
Yan K, Lim DW and Ma BBBY
Nasopharyngeal carcinoma (NPC) remains an endemic disease in certain parts of the world, with many patients presenting with advanced disease on diagnosis. Chemotherapy had remained the standard of care with minimal progress made until recent years. This review aims to provide an overview of recent significant breakthroughs and up-and-coming novel strategies in treating this deadly disease.
Assessing the clinical potential of plozasiran, an siRNA therapy for severe hypertriglyceridemia
Tang XL, Hooper AJ and Burnett JR
Theranostic strategies in sarcoma: preliminary clinical evidence
Filippi L, Ferrari C and Rubini G
Sarcomas encompass a highly diverse range of malignancies, characterized by varied morphological and molecular profiles. Treatment options in case of therapy-refractory or advanced disease are limited. In this context, theranostics emerges as an innovative platform seamlessly integrating diagnosis and therapy, offering promising prospects.
Protein phosphatase 2A activators under investigation for smoking-related chronic obstructive pulmonary disease and related disorders
Antoniu S and Rascu S
Chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation during therapy. Cystic fibrosis (CF), alpha-one antitrypsin deficiency (AATD), and non-CF bronchiectasis are also chronic respiratory disorders with inflammation and progression that share many similarities with COPD. Therefore, various anti-inflammatory approaches are currently being investigated, and protein phosphatase 2A (PP2A) activators may represent one such approach.
Management of inflammaging in kidney diseases: focusing on the current investigational drugs
Shelke V, Dagar N, Lech M and Gaikwad AB
To improve kidney disease treatments, it is crucial to understand how inflammaging affects patients´ longevity. We could potentially slow down kidney disease progression and enhance longevity by targeting specific pathways involved in inflammaging with potential drugs.
Dual blockade of endothelin A and angiotensin II type 1 receptors with sparsentan as a novel treatment strategy to alleviate IgA nephropathy
Nagasawa H, Suzuki H, Ueda S and Suzuki Y
Although immunoglobulin A nephropathy (IgAN) had been discovered more than 50 years ago, 30-40% of IgAN patients still have primary glomerular disease that progresses to end-stage renal disease. However, various treatment strategies for IgAN have rapidly expanded in recent years to include endothelin (ET) receptor antagonists.
Targeting a key FAK-tor: the therapeutic potential of combining focal adhesion kinase (FAK) inhibitors and chemotherapy for chemoresistant non-small cell lung cancer
Geijerman E, Terrana F, Peters GJ, Deng D, Diana P, Giovannetti E and Xu G
NSCLC is the leading cause of cancer-related deaths globally, with a low survival rate primarily due to NSCLC frequently becoming chemoresistant. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in pathways regulating multiple processes in the cell, including survival, migration, and the TME, that contribute to both tumor progression and drug resistance. Recently, FAK inhibitors (FAKi) have shown promising potential for the treatment of NSCLC.
Olaparib monotherapy or in combination with abiraterone for treating mutated metastatic castration-resistant prostate cancer: alone or stronger together?
Fenton SE and Hussain M
Prostate cancer has entered the era of precision medicine with the introduction of PARP inhibitors for patients with specific mutations in genes associated with DNA damage repair. Recent studies have shown benefit in combination therapy with PARP inhibitors like olaparib and antiandrogens like abiraterone.
Recent progress in tyrosine kinase 2 inhibitors for atopic dermatitis
Liu Q, Xia Y, Liu L, Zhou Y and Li Y
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by persistent itching. Conventional treatments for AD include topical corticosteroids and calcineurin inhibitors, but there are emerging therapies targeting the JAK-TYK2 pathway that are promising for the treatment of AD.
A four-in-one first-in-human study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and concentration-QTc relationship of HRS-1780, a selective non-steroidal mineralocorticoid receptor antagonist, in healthy men
Shen Q, Li L, Qian W, Dong X, Bao M, Huang R, Li N, Ye Z, Cheng G, Wang Q, Shen K and Luo Z
This first-in-human study evaluated HRS-1780, an oral selective non-steroidal mineralocorticoid receptor antagonist, in healthy men.
Experimental drugs for erosive esophagitis: what is in the clinical development pipeline?
Simadibrata DM, Lesmana E and Lee YY
Proton pump inhibitor (PPI) has revolutionized the treatment of erosive esophagitis (EE) in the past few decades. However, roughly 30-40% of the patients, especially those with severe EE (Los Angeles Grade C/D), remain poorly responsive to this medication. Novel drugs have been formulated and/or repurposed to address this problem.
The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects
Ma T, Weng Z, Cao B, Dong Y, Deng C, Huang L, Yang Y, Wang Y, Shen C, Wang L, Shen K and Li J
Inhibiting the coagulation factor XI (FXI) is a novel strategy for prevention and treatment of thromboembolism without affecting extrinsic coagulation pathways. SHR-2004 is a humanized monoclonal antibody that selectively binds to FXI and factor XIa (FXIa).
Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose riliprubart, an anti-C1s humanized monoclonal antibody in East-Asian adults: results from a Phase 1, randomized, open-label trial
Li Y, Young Na J, Zhu Y, Oh J, Zhao A, Jang IJ and Tang L
This Phase 1 trial was planned to investigate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a single dose of riliprubart in healthy East-Asian adult participants.
Application of engineered antibodies (scFvs and nanobodies) targeting pathological protein aggregates in Alzheimer's disease
Zhang Y, Yu W, Zhang L and Li P
The misfolding and aggregation of proteins are associated with various neurodegenerative diseases, such as Alzheimer's disease (AD). The small-molecule engineered antibodies, such as single-chain fragment variable (scFv) antibodies and nanobodies (Nbs), have gained attention in recent years due to their strong conformational specificity, ability to cross the blood-brain barrier (BBB), low immunogenicity, and enhanced proximity to active sites within aggregates.
Investigational new drugs for the treatment of leishmaniasis
Sundar S, Singh VK, Agrawal N, Singh OP and Kumar R
Over the past 20 years, significant progress has been made in anti-leishmanial therapy. Three new drugs/formulations are available for the treatment of various forms of leishmaniasis, namely oral miltefosine, paromomycin and liposomal amphotericin B. However, these advances in drug development have added considerable complexity for clinicians including toxicity, emergence of resistance and decreased sensitivity of available drugs. The development of newer drugs with less toxicity and more efficacy is urgently needed.
MASLD and MASH: how a change of nomenclature may impact our approach in treating liver disease
Dale K, Fallouh Y and Alkhouri N
Factor IX stimulants in preclinical and early phase trials for hemophilia B treatment
Franchini M and Focosi D
Hemophilia B is a X-linked rare inherited bleeding disorder characterized by coagulation factor IX (FIX) deficiency. Therapy for hemophilia B is aimed at replacing the FIX deficiency by means of several plasma-derived or recombinant FIX products. The recent availability of recombinant FIX concentrates with a prolonged FIX half-life represented a great technological advance, permitting more spaced drug infusions and reducing treatment burden among hemophilia B patients.
Zanzalintinib (XL092): a next-generation tyrosine kinase inhibitor-comprehensive review of early safety & efficacy data
Yu J, Park R, Tojjari A, Sadeghipour A, Saeed A and Saeed A
Zanzalintinib (XL092) is a next-generation anti-VEGFR-related multi-targeted TKI that exhibits immunomodulatory effects.
Antiviral agents and therapeutics against respiratory viruses
Tripp RA and Martin DE
Respiratory viruses are responsible for significant worldwide morbidity and mortality. While vaccines are highly effective at reducing the morbidity and mortality associated with viral infections, this protection is incomplete. It requires a high degree of compliance, which is hindered by vaccine hesitancy. To address these gaps, antiviral agents and therapeutics are crucial in combating diseases caused by respiratory viruses. Antiviral agents are broadly classified into two groups: 1) direct-acting antivirals (DAA) and 2) host-directed antivirals (HDA).