Endometriosis is a chronic, relapsing inflammatory disease requiring sustained hormonal suppression, yet first-line management remains dominated by daily oral progestins designed for short-acting use. Although pharmacologically effective, long-term outcomes are frequently compromised by fluctuating exposure, tolerability-driven discontinuation, and poor persistence. This narrative comparative review examines first-line progestins across efficacy, safety, tolerability, and persistence, alongside long-acting platforms including intrauterine systems, vaginal rings, implants, injectables, and emerging depots. Relevant clinical, pharmacokinetic, adherence, formulation, and preclinical evidence was identified through iterative literature searches. By synthesizing clinical, pharmacokinetic, and adherence evidence within a unified translational framework, we identify formulation-driven gaps that may influence exposure stability and therapeutic durability. The analysis distinguishes delivery-modifiable constraints from biological limitations such as progesterone resistance and disease heterogeneity, and outlines priorities for next-generation formulation development. Aligning delivery architecture with disease chronicity may offer a pragmatic, scalable, and clinically impactful pathway to strengthen established progestin therapies while complementing molecular innovation. Interpretation is limited by heterogeneity in study populations, endpoints, and treatment durations, and by limited endometriosis-specific clinical evidence for several emerging delivery platforms.
Menopausal vasomotor symptoms (VMS) are common and can substantially impair health-related quality of life through negative effects on sleep, mood, cognition, daily activities and long-term health outcomes. Menopausal hormonal therapy (MHT) is the first-line treatment for VMS in patients aged < 60 years and within 10 years of menopause onset. Decisions regarding MHT use and formulation should be individualised to each patient according to age, symptoms, time since menopause onset and individual risk factors and medical history. For patients in whom MHT is contraindicated or not preferred, non-hormonal drugs, such as paroxetine, fezolinetant and elinzanetant, offer effective alternative treatment options. Although several non-hormonal drugs are used off label to treat VMS, novel non-hormonal drugs are under investigation and may further expand treatment options.
Combined hepatocellular–cholangiocarcinoma (cHCC-CCA) is a rare liver cancer characterized by cancerous cells of bile duct origin. Treatment options are limited and prognosis is poor. When a mutation of isocitrate dehydrogenase-1 (IDH1) is present, the patient may be eligible for treatment with ivosidenib, an IDH1 inhibitor. Ivosidenib improved overall survival versus placebo in patients with previously treated advanced CCA with IDH1 mutation in the ClarIDHy phase III trial. We describe the case of a male patient aged 55 years diagnosed with cHCC-CCA with an IDH1 pathogenic mutation who failed first-line treatment with cisplatin plus gemcitabine. Ivosidenib 500 mg once daily treatment was initiated, and after 3 months, partial regression of the target lesion was observed, and after 22 months, best overall response was partial remission. No adverse events were reported. After 35 months, the patient continued to receive ivosidenib since the target lesion had not progressed, and treatment was very well tolerated. Ivosidenib appeared to be an effective and well-tolerated treatment for this patient with previously treated cHCC-CCA who had IDH1 mutations.
Gepotidacin (BLUJEPA), a first-in-class triazaacenaphthylene inhibitor of type II bacterial topoisomerases, is a useful addition to the antimicrobials currently approved in the USA and UK for the treatment of uncomplicated urinary tract infections (uUTIs) in female adult and paediatric patients ≥ 12 years of age weighing ≥ 40 kg, and in the USA for the treatment of uncomplicated urogenital gonorrhoea (uUG) in adult and paediatric patients ≥ 12 years of age weighing ≥ 45 kg who have limited or no alternative treatment options. In the pivotal phase 3 EAGLE-2 and EAGLE-3 trials in uUTIs, gepotidacin was non-inferior to nitrofurantoin for achieving patient therapeutic responses (combined clinical and microbiological success) and superior to nitrofurantoin in EAGLE-3. Additionally, in the pivotal phase 3 EAGLE-1 trial in the treatment of uUG, gepotidacin was non-inferior to ceftriaxone plus azithromycin in achieving microbiological success. The tolerability of gepotidacin was acceptable, with gastrointestinal events being the most common type of adverse event. New antimicrobials are needed to combat rising rates of antimicrobial resistance among bacteria that cause diseases, such as urinary tract infection and gonorrhoea. Gepotidacin (BLUJEPA) is the first in a new class of antimicrobials that targets type II bacterial topoisomerases, and has been approved for treatment of uncomplicated urinary tract infections (uUTIs) in female patients ≥ 12 years of age and weighing ≥ 40 kg in the USA and UK, as well as for the treatment of uncomplicated urogenital gonorrhoea (uUG) in patients ≥ 12 years of age and weighing ≥ 45 kg who have limited or no alternative treatment options in the USA. In clinical trials, gepotidacin was non-inferior to first-line treatments nitrofurantoin for uUTIs and ceftriaxone plus azithromycin for uUG. It had at least as good or better rates of therapeutic success (measured by combined symptomatic cure and eradication of the disease-causing bacteria) in the treatment of uUTIs, and at least as good rates of bacterial eradication for uUG compared with first-line treatments. Gepotidacin had acceptable tolerability, with diarrhoea, nausea and abdominal pain being the most common adverse events. Overall, gepotidacin is a useful addition to the antimicrobials currently available to treat patients with uUTIs and uUG.
Guselkumab (TREMFYA®), a first-in-class interleukin-23 (IL-23) antagonist, is a monoclonal antibody that expands the treatment options available for the systemic treatment of moderate-to-severe plaque psoriasis in paediatric patients ≥ 6 years of age who are candidates for systemic therapy in the EU and paediatric patients ≥ 6 years of age who weigh ≥ 40 kg and are candidates for systemic therapy or phototherapy in the USA. As shown in the randomized, placebo-controlled, multicentre, phase III PROTOSTAR trial, subcutaneous guselkumab significantly reduced disease severity compared with placebo at week 16 of treatment, meeting all co-primary and key secondary endpoints relating to Investigator Global Assessment score (clear or almost clear skin) and Psoriasis Area and Severity Index scores (≥ 75
