Pediatric clinical trial update: Q2 2026

The second quarter of 2026 brought a dense stream of clinical trial developments with potential implications for pediatric care, spanning rare metabolic and skeletal disorders, neurology, endocrinology, gastroenterology, neuromuscular disease, and infectious disease prevention. From durable hormone control in congenital adrenal hyperplasia and sustained growth gains in skeletal dysplasias to early gene therapy signals in inherited deafness and urea cycle disorders, investigators reported findings across the development spectrum—from first-in-human and preclinical work to pivotal phase 3 readouts that could shape regulatory decisions in the back half of the year.

This quarterly clinical trial recap highlights the key studies, trial results, and pipeline developments reported during Q2 2026 that pediatricians should have on their radar.

1. Berdazimer gel improves clearance rates in phase 3 molluscum contagiosum trial

Topline results from the phase 3 B-SIMPLE4 trial demonstrated that berdazimer 10.3% topical gel improved complete lesion clearance in patients aged 6 months and older with molluscum contagiosum, meeting its primary endpoint at 12 weeks. Among 891 participants, 32.4% of patients treated with berdazimer achieved complete resolution of all lesions compared with 19.7% of those receiving vehicle.

Pooled analyses from multiple randomized studies showed similar findings, with complete clearance rates of approximately 30.0% vs 19.8%, respectively. Benefits were observed across demographic and clinical subgroups, including children with atopic dermatitis, and patient-reported outcomes indicated greater perceived improvement with active treatment. Berdazimer was generally well tolerated, with adverse events primarily limited to mild application-site reactions, supporting its potential role as a noninvasive treatment option for pediatric patients with molluscum contagiosum.

2. Crinecerfont shows durable hormone control, lower steroid doses in pediatric CAH at 2 years

Two-year results from the phase 3 CAHtalyst Pediatric open-label extension demonstrated that crinecerfont (Crenessity) provided durable hormonal control while allowing reductions in glucocorticoid exposure among children and adolescents with classic congenital adrenal hyperplasia (CAH). Among 86 patients aged 4 to 17 years, treatment was associated with sustained decreases in adrenocorticotropic hormone and 17-hydroxyprogesterone levels through 24 months, alongside a mean reduction of 3.2 mg/m²/day in glucocorticoid dosing.

Investigators also reported improvements in cardiometabolic outcomes, with 60% of overweight or obese participants achieving clinically meaningful reductions in BMI standard deviation scores and 61% of those with baseline insulin resistance no longer meeting criteria for insulin resistance after 2 years. Additional benefits included improvements in acne severity and androgen-related measures, while no new safety signals emerged and study retention exceeded 80%. The findings provide the longest pediatric follow-up to date for crinecerfont and support its role as a steroid-sparing treatment option for children with classic CAH.

3. Ersodetug misses primary endpoint in phase 3 sunRIZE trial for congenital hyperinsulinism

Expanded analyses from the phase 3 sunRIZE trial suggest that ersodetug, an investigational allosteric insulin receptor antagonist, may improve glycemic control in patients with congenital hyperinsulinism despite the study not meeting its primary endpoint. The randomized, placebo-controlled trial enrolled 63 patients aged 3 months to 45 years and evaluated ersodetug as an add-on to standard therapy.

While the primary self-monitored blood glucose–based endpoint was not achieved, continuous glucose monitoring analyses demonstrated reductions in hypoglycemia, increased time spent in normoglycemia, and higher average glucose levels compared with placebo. Investigators also reported encouraging findings from the ongoing open-label extension, with nearly all study completers electing to continue treatment and preliminary data suggesting sustained glycemic benefits alongside reductions in background therapies such as diazoxide, somatostatin analogs, and tube feeding support. Although the regulatory pathway remains uncertain, the results highlight the potential of ersodetug as a novel treatment approach for congenital hyperinsulinism, a rare disorder with limited therapeutic options.

4. TransCon CNP shows sustained growth gains in children 5 years and older with achondroplasia

Two-year results from the pivotal ApproaCH trial showed that once-weekly TransCon CNP (navepegritide) produced sustained improvements in growth among children aged 5 years and older with achondroplasia. In the phase 3 study, children treated with TransCon CNP achieved significantly greater annualized growth velocity at 52 weeks compared with placebo, with gains maintained through 104 weeks during the open-label extension. Improvements were also observed in achondroplasia-specific and CDC-based height z-scores, indicating continued progress in linear growth over time.

The therapy demonstrated a favorable safety profile through 2 years, with mostly mild or moderate adverse events, low rates of mild injection-site reactions, no symptomatic hypotension, and no evidence of accelerated bone age. The findings further support the long-term efficacy and tolerability of TransCon CNP, which received FDA approval in February 2026 for pediatric patients aged 2 years and older with achondroplasia and open epiphyses.

5. ABS-1230 enters phase 1b/2 testing in KCNT1-related epilepsy amid FDA rare disease planning

Actio Biosciences announced the initiation of the phase 1b/2 KYRON trial evaluating ABS-1230, an investigational small-molecule KCNT1 inhibitor, in children and young adults with genetically confirmed KCNT1-related epilepsy. The study will enroll patients aged 1 month to 21 years and includes an open-label treatment period, a randomized placebo-controlled phase, and an optional open-label extension, with assessments focused on safety, pharmacokinetics, seizure activity, and neurodevelopmental outcomes.

Although no efficacy data are yet available, the program represents an important step toward a genotype-directed treatment approach for a rare developmental and epileptic encephalopathy characterized by severe, often treatment-resistant seizures and significant neurodevelopmental impairment. Early phase 1a data in healthy volunteers showed favorable tolerability with no serious adverse events reported, and the program has been accepted into the FDA's Rare Disease Evidence Principles framework, which is designed to support drug development in ultrarare genetic disorders. The trial marks an early-stage effort to address a significant unmet need in pediatric epilepsy, where disease-specific treatment options remain limited.

6. AK-OTOF shows early hearing restoration potential in children with OTOF-mediated hearing loss

Preliminary findings from the phase 1/2 AK-OTOF-101 trial suggest that AK-OTOF, an investigational gene therapy for OTOF-mediated sensorineural hearing loss, may restore functional hearing in children with inherited deafness. Data presented from 18 participants who received bilateral treatment showed that 80% of those receiving the higher dose achieved hearing improvement to at least a moderate hearing loss level, with auditory responses observed as early as 30 days after administration.

According to investigators, improvements in auditory brainstem responses and behavioral hearing measures have remained stable or continued to improve over follow-up, with some participants now monitored for up to 2 years. The therapy was generally well tolerated, with no serious adverse events related to treatment, delivery, or the administration procedure reported. Although the trial remains ongoing, the findings highlight the potential of gene therapy to address the underlying genetic cause of hearing loss and may signal a future shift toward precision medicine approaches for children with inherited forms of deafness.

7. RVL-001 enters early n-of-1 studies for Rett syndrome and Pitt-Hopkins syndrome

Unravel Biosciences has initiated 2 early proof-of-concept studies evaluating RVL-001, a proprietary formulation of the histone deacetylase inhibitor vorinostat, in patients with Rett syndrome and Pitt-Hopkins syndrome. The placebo-controlled n-of-1 trials are expected to enroll 15 patients with Rett syndrome and 5 with Pitt-Hopkins syndrome and will assess the potential of epigenetic modulation as a treatment strategy for these rare neurodevelopmental disorders. The studies represent an early-stage effort to address significant unmet needs, particularly in Pitt-Hopkins syndrome, which currently has no approved disease-directed therapies.

Although no efficacy data are available, the program is based on the hypothesis that targeting transcriptional dysregulation may improve disease manifestations associated with MECP2 and TCF4 abnormalities. Investigators anticipate study completion in early 2027, with results expected to provide initial insights into the safety and potential clinical activity of RVL-001 in these ultra-rare pediatric populations.

8. Phase 2b UK trial to test Lactin-V for preterm birth prevention

Researchers in the United Kingdom have launched FLIP-2, a phase 2b randomized, placebo-controlled trial evaluating whether Lactin-V, a vaginal live biotherapeutic containing Lactobacillus crispatus CTV-05, can reduce the risk of preterm birth in pregnant patients at high risk for early delivery. The study will enroll 360 participants across 4 maternity centers and builds on findings from the earlier FLIP-1 pilot study, which demonstrated that Lactin-V was generally well tolerated and acceptable during pregnancy. The therapy is designed to restore a vaginal microbiome dominated by L crispatus, a bacterial species associated with lower levels of genital tract inflammation and potentially improved pregnancy outcomes.

Although the biologic rationale is promising, it remains unclear whether microbiome modification can meaningfully reduce preterm birth rates. The trial represents an important effort to address a significant unmet need in obstetric care, particularly as treatment options for preterm birth prevention remain limited following the withdrawal of hydroxyprogesterone caproate from the US market.

9. RGX-202 demonstrates positive phase 3 results for Duchenne muscular dystrophy

Topline results from the pivotal phase 3 portion of the AFFINITY DUCHENNE study showed that the investigational gene therapy RGX-202 met its primary biomarker endpoint in ambulatory boys with Duchenne muscular dystrophy (DMD), with 93% of treated participants achieving greater than 10% microdystrophin expression at 12 weeks. Investigators reported a mean microdystrophin expression level of 71.1% and observed a correlation between early microdystrophin expression and functional outcomes at 1 year.

Preliminary analyses of a small subset of participants suggested improvements in motor function measures, including the North Star Ambulatory Assessment, compared with external controls. RGX-202 was generally well tolerated, although 2 serious adverse events—subacute myocarditis and asymptomatic liver injury—were reported and resolved without long-term complications. While the findings support continued development of RGX-202 and add to growing evidence surrounding microdystrophin-based gene therapies in DMD, longer-term follow-up and confirmatory clinical data will be needed to establish the durability of benefit and inform future regulatory decisions.

10. Preclinical DMD gene therapy GB703 debuts as GEMMABio advances SMA program

Gemma Biotherapeutics presented new preclinical data on 2 investigational gene therapy programs targeting neuromuscular disorders: GB703 for Duchenne muscular dystrophy (DMD) and GB221 for spinal muscular atrophy type 1 (SMA1). Preclinical findings for GB703 demonstrated muscle-targeted delivery and expression of a hybrid micro-utro/dystrophin transgene, with evidence of improved muscle function markers and restoration of key structural proteins in animal models of DMD. The company said the data support advancement toward investigational new drug–enabling studies.

For SMA1, preclinical data for GB221 showed prolonged survival, improved motor function, and favorable biodistribution in animal models, while early findings suggested a strategy designed to reduce dorsal root ganglia toxicity, a known challenge in systemic gene therapy. GB221 is currently being evaluated in the phase 1/2 CHARISMA trial in infants with SMA1. Although both programs remain in the early stages of development, the results highlight ongoing efforts to improve the safety, targeting, and effectiveness of next-generation gene therapies for pediatric neuromuscular diseases.

11. BMN 401 raises plasma PPi but misses skeletal end point in pediatric ENPP1 deficiency

Results from the pivotal phase 3 ENERGY 3 trial showed that BMN 401, an investigational enzyme replacement therapy for ENPP1 deficiency, successfully increased plasma inorganic pyrophosphate (PPi) levels but did not demonstrate a corresponding improvement in skeletal disease over 52 weeks. In the study of 27 children aged 1 to 12 years, BMN 401 met 1 of its 2 co-primary endpoints by significantly improving the biochemical marker PPi compared with conventional therapy.

However, the therapy failed to show benefit on the Radiographic Global Impression of Change score, a measure of clinically meaningful improvement in rickets severity, and no favorable trends were observed across secondary endpoints evaluating rickets severity or growth. BMN 401 was generally well tolerated, with no new safety concerns reported. The findings highlight the challenges of translating biomarker improvements into measurable clinical outcomes in rare pediatric disorders and raise important questions about the relationship between biochemical correction and skeletal benefit in children with ENPP1 deficiency.

12. ECUR-506 shows early response in neonatal-onset OTC deficiency trial

Preliminary data from the ongoing OTC-HOPE trial suggest that ECUR-506, an investigational in vivo gene insertion therapy, may reduce metabolic crises in infants with severe neonatal-onset ornithine transcarbamylase (OTC) deficiency. In the first completed low-dose cohort, 3 treated infants experienced a 57% reduction in annualized hyperammonemic events and a 65% reduction in hyperammonemic crises compared with pretreatment rates. Two participants remained free of both event types after treatment, while one infant reportedly discontinued ammonia-scavenging therapy, liberalized dietary protein intake, and remained free of hyperammonemic events through 18 months of follow-up.

Across 7 treated participants spanning multiple dose cohorts, investigators reported no unexpected treatment-related safety concerns, infusion reactions, or thrombotic microangiopathy. Although the findings are based on a small, uncontrolled cohort, they provide early evidence that targeted gene insertion may offer a novel approach to reducing disease burden in neonatal-onset OTC deficiency, a rare and life-threatening urea cycle disorder with limited treatment options beyond intensive medical management and liver transplantation.

13. Zovegalisib shows early promise in PIK3CA-driven vascular anomalies

Initial phase 2 data from the ReInspire trial suggest that zovegalisib, an investigational PI3Kα mutant-selective inhibitor, may provide meaningful clinical benefit for patients with PIK3CA-driven vascular anomalies, including PIK3CA-related overgrowth spectrum, lymphatic malformations, and venous malformations. Among 20 response-evaluable adolescents and adults aged 12 years and older, 60% achieved at least a 20% reduction in lesion volume at 12 weeks, with 95% experiencing some degree of lesion shrinkage.

Investigators also reported improvements in patient- and clinician-reported outcomes, including pain and overall disease status. The treatment demonstrated a favorable safety profile at the 100-mg and 300-mg twice-daily doses, with few serious treatment-related adverse events and no reported grade 3 hyperglycemia or diarrhea in these cohorts. Although enrollment is ongoing and pediatric expansion cohorts are still being evaluated, the early findings support continued development of zovegalisib as a potential targeted therapy for patients with PIK3CA-driven vascular anomalies, a group of rare disorders with limited long-term treatment options.

14. Phase 3 trial shows vosoritide improves growth in children with hypochondroplasia

Positive phase 3 results from the CANOPY-HCH-3 trial demonstrated that vosoritide (VOXZOGO) significantly improved growth outcomes in children with hypochondroplasia, a rare skeletal dysplasia for which no approved therapies currently exist. In the global randomized, placebo-controlled study of 80 children aged 3 to 17 years, treatment with vosoritide resulted in a statistically significant increase in annualized growth velocity compared with placebo, with a least squares mean difference of 2.33 cm per year after 52 weeks.

Investigators also reported significant improvements in standing height, height Z-scores, and arm span, a secondary endpoint that may have implications for daily function and independence. The safety profile was consistent with previous experience in achondroplasia, with no new safety signals identified. Based on these findings, BioMarin plans to submit a supplemental New Drug Application to the FDA in the third quarter of 2026, positioning vosoritide as a potential first approved therapy for children with hypochondroplasia.

A follow-up readout presented later in the quarter at ENDO 2026 added longer-term context: a separate, investigator-sponsored phase 2 extension study of 13 children with hypochondroplasia, led by researchers at Children's National Hospital, reported a mean height standard deviation score improvement of 0.72 SD over 3 years, with annualized growth velocity rising from 4.27 cm/y at baseline to 7.24 cm/y at year 1 (P < .001) and remaining above baseline through years 2 and 3. BioMarin said these longer-term, nonregistrational data will complement the CANOPY-HCH-3 results in the planned FDA submission. At the same meeting, the company also reported early phase 1 single-ascending-dose data in healthy adults for BMN 333, an investigational long-acting CNP analog being developed for achondroplasia; at the highest evaluated dose, exposure to free CNP was more than 13-fold higher than that of another long-acting CNP agent, and BioMarin began enrolling patients in a registration-enabling phase 2/3 study of BMN 333 in April, with a dose-finding update expected in 2027.

15. Ecopipam phase 3 data demonstrates reduced Tourette relapse risk in youth

Results from a phase 3 randomized-withdrawal trial suggest that continued treatment with ecopipam, an investigational dopamine D1 receptor antagonist, may help maintain tic control and reduce relapse risk in children and adolescents with Tourette syndrome. After an initial 12-week open-label treatment period involving 216 participants, including 167 pediatric patients, responders were randomized to continue ecopipam or switch to placebo. Investigators reported that patients who remained on ecopipam experienced a 50% lower risk of relapse than those transitioned to placebo.

The therapy was generally well tolerated, with adverse events described as mild to moderate and consistent with previous studies. Unlike currently approved Tourette syndrome medications, which primarily target dopamine D2 receptors, ecopipam acts through a distinct D1 receptor mechanism and may offer an alternative approach to tic management. The findings, published in JAMA Neurology, are expected to support a planned FDA submission and position ecopipam as a potential new treatment option for pediatric patients with Tourette syndrome.

16. ALYFTREK phase 3 data support pediatric CFTR modulator submissions

Vertex Pharmaceuticals reported new phase 3 data for vanzacaftor/tezacaftor/deutivacaftor (ALYFTREK) in children aged 2 to 5 years with cystic fibrosis (CF) and responsive CFTR genotypes, presented at the European Cystic Fibrosis Conference. The company said it plans to begin global regulatory submissions for this pediatric age group in the first half of 2026. ALYFTREK is a once-daily triple CFTR modulator regimen currently indicated in the US for patients aged 6 years or older; its use in children aged 2 to 5 years remains investigational.

In the 24-week, phase 3, open-label study, 67 children completed treatment, with safety and tolerability as the primary endpoint; findings were consistent with the regimen's established safety profile. Children entered the study from a baseline on elexacaftor/tezacaftor/ivacaftor (TRIKAFTA), and ALYFTREK treatment was associated with a mean sweat chloride reduction of −9.6 mmol/L through week 24. Vertex reported that 92% of participants achieved sweat chloride concentrations below 60 mmol/L and 65% reached below 30 mmol/L. Because participants were already on TRIKAFTA at baseline, this incremental change should be interpreted as improvement over an already highly effective regimen rather than treatment-naive efficacy; the open-label design and small sample size also limit conclusions about longer-term effects on pulmonary exacerbations, growth, or nutrition.

In a separate pediatric update, Vertex presented 24-week phase 3 results for TRIKAFTA itself in 54 children aged 12 to younger than 24 months who were modulator-naive at baseline. Treatment was associated with a mean sweat chloride reduction of −71.8 mmol/L; 98.0% of children achieved concentrations below 60 mmol/L, and 68.6% reached below 30 mmol/L. Vertex said it has initiated global regulatory submissions for TRIKAFTA in this younger age group. For clinicians, the data point to continued movement of CFTR modulation into younger age groups, but regulatory review and peer-reviewed publication will be needed before practice implications can be fully assessed.

17. ADA 2026 data highlight pediatric outcomes and treatment satisfaction with Afrezza

Following the FDA's May 2026 approval of Afrezza (insulin human) Inhalation Powder for children and adolescents aged 6 years and older, MannKind Corporation presented new subgroup and satisfaction analyses from the phase 3 INHALE-1 trial at the American Diabetes Association 2026 Scientific Sessions. According to company representatives, pulmonary function testing showed no difference between inhaled insulin and subcutaneous insulin users, and there was no difference in CGM-measured hypoglycemia between groups, suggesting no new pediatric safety signals relative to prior adult data.

The most common adverse event was mild, typically transient cough, reported in roughly 1 in 5 children. Company representatives also said that both parents of younger children and teen patients reported greater treatment satisfaction with inhaled insulin relative to subcutaneous insulin, along with less weight gain, and noted that middle- and high-school-age patients—a historically difficult group to manage, with more than 80% not meeting glycemic targets—appeared to benefit from the ability to dose immediately before eating rather than in advance. Subgroup analyses also suggested more comparable HbA1c outcomes between inhaled and subcutaneous insulin among patients with higher baseline A1c who may be less engaged in day-to-day management. As with other industry-presented conference data, independent peer-reviewed publication of the full pediatric dataset will be important for fully contextualizing these findings.

18. Setmelanotide shows interim phase 2 signals in Prader-Willi syndrome

Rhythm Pharmaceuticals reported 6-month interim data from an ongoing phase 2 trial of setmelanotide, a melanocortin-4 receptor (MC4R) agonist, in 18 children, adolescents, and young adults aged 6 to 23 years with Prader-Willi syndrome (PWS), presented at ENDO 2026. At month 6, the company reported a mean BMI reduction of 3.06% among 17 treated participants, with pediatric participants showing a mean BMI z-score reduction of 0.35. Body composition scans available for 16 participants showed mean fat mass decreased by 4.19% while lean mass increased by 0.74%.

Among 10 participants with moderate to severe baseline hyperphagia, 8 achieved at least a 7-point reduction on the Hyperphagia Questionnaire for Clinical Trials, characterized by the company as clinically meaningful; anxiety and behavioral dysregulation, assessed with the PWS Anxiousness and Distress Behaviors Questionnaire, also improved in 10 of 15 participants with elevated baseline scores. The trial is small, ongoing, and the company announcement did not describe a placebo comparator or detailed PWS-specific adverse event rates. Setmelanotide is already FDA approved for several rare genetic obesity indications, including Bardet-Biedl syndrome and POMC, PCSK1, or LEPR deficiency, but is not approved for PWS. A larger, controlled phase 3 program with prespecified endpoints will be needed to confirm durability and clinical benefit.

19. Diazoxide choline data show durable hyperphagia gains in Prader-Willi syndrome

New late-breaking data presented at ENDO 2026 showed that patients with PWS who restarted diazoxide choline extended-release tablets (VYKAT XR) after a randomized withdrawal period regained improvements in hyperphagia, with effects reported through 2 years of follow-up, according to Neurocrine Biosciences and Soleno Therapeutics. The data come from Study C614, an open-label long-term extension that followed a sequential phase 3 program (C601, C602-OLE, and a 16-week randomized withdrawal period) and enrolled 77 participants with a mean age of 15.3 years.

Among participants who restarted VYKAT XR after placebo withdrawal, the mean Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score improved by a mean of −4.5 points at week 13, with additional gains to −6.3 points by 2 years. Participants who remained on continuous therapy throughout had smaller initial changes but sustained improvement, reaching −3.1 points at 2 years. Separate analyses comparing treated participants with external controls from the PATH for PWS Natural History Study reported adjusted treatment differences favoring VYKAT XR of roughly 6 points on the HQ-CT at years 1 through 3 (P < .0001 at all time points), as well as significant differences across all 6 PWS Profile behavioral domains. VYKAT XR was approved by the FDA in March 2025 for hyperphagia in patients aged 4 years and older with PWS. For clinicians, the comparisons with natural history controls—rather than randomized concurrent controls—warrant cautious interpretation, even as the data add to a growing body of longer-term follow-up in this difficult-to-treat population.

Taken together, Q2 2026 underscored 2 parallel currents in pediatric drug development: continued maturation of therapies for skeletal dysplasias and Prader-Willi syndrome, where multiple competing and complementary agents reported overlapping efficacy data within the same several weeks, and an expanding wave of early-phase gene therapy and genotype-directed programs—spanning hearing loss, urea cycle disorders, neuromuscular disease, and ultrarare epilepsies—that remain years from potential approval but reflect a broadening precision-medicine pipeline for children with rare disease.