Latest news with #AACE
Medscape
27-05-2025
- Health
- Medscape
Can Endocrine NP Training Help Ease Provider Shortage?
ORLANDO, Fla. — A program at Duke University School of Nursing, Durham, North Carolina, is currently one of just two in the United States that trains nurse practitioners (NPs) to provide endocrine specialty care, but more could be on the way. Established in 2016, the program was 'a result of national demand for diabetes and endocrinology providers,' Program Founder and Director Kathryn Evans Kreider, DNP, APRN, FAANP, said at American Association of Clinical Endocrinology (AACE) Annual Meeting 2025. Downward trends in endocrinology fellowship recruitment concurrent with increases in endocrine diseases, including diabetes, obesity, and osteoporosis, have led to acute shortages of endocrinology providers in many parts of the country. Recent data suggest that 70% of US counties have no endocrinologists. Kreider, who is a professor of nursing at Duke, told Medscape Medical News , 'My program has always been a combination of advanced diabetes management and general endocrine. I felt very strongly about that because we need NPs out in the world who are able to see these more complex patients. We do not replace endocrinologists. We just know that there's a huge shortage of endocrinologists, and we have to figure out better ways to meet that access gap.' Asked to comment, Session Moderator Yael Tobi Harris, MD, PhD, associate professor of medicine at the Zucker School of Medicine and chief of the Division of Endocrinology, Diabetes and Metabolism at Hofstra/Northwell, Great Neck, New York, told Medscape Medical News that she supports this type of program. 'I am a physician and I'm a huge fan. We really have a drastic shortage of endocrine providers, and we just cannot meet the demand that is out there for endocrine care. Nurse practitioners are well-trained clinicians and well-suited to deliver endocrine care. It really helps increase access.' Also asked for input, Matthew J. Levine, MD, endocrinology fellowship director and clinical professor of medicine at Scripps Clinic, La Jolla, California, said, 'There was an uptick in endocrinology fellowship applicants in the last recruitment cycle, and between that and ongoing efforts to increase the endocrinologist pipeline, we hope that this is the beginning of a positive trend to address the shortage. Endocrine NPs can and do certainly help to fill the shortage as well, especially in medically underserved areas.' However, Levine, who is also president of the Association of Program Directors in Endocrinology, Diabetes and Metabolism, added, 'I would have reservations about them providing care as solo practitioners. With only 1 year or so of training and given that endocrinology is a complex specialty with longitudinal management of intersecting comorbidities, it is best for them to work as part of an endocrine care team with an endocrinologist who went through multiple years of multifaceted training being the leader of said care team.' According to Harris, 'What matters is whether the patients are receiving the care, and if reserving that for physicians only means that patients don't get care, I don't see what the value is in that. The concern that [advanced practice providers] didn't go to medical school seems somewhat misguided to me, particularly when we have programs like Dr Kreider's that are providing the training.' Training NPs in Endocrinology: Wave of the Future? There are currently about 385,000 NPs in the United States compared with roughly 1.1 million physicians. About 70% of NPs are in primary care, while 30% practice specialty care, most commonly in gerontology or psychiatry/mental health. 'The vast majority of nurse practitioners are trained in primary care, so those who go into specialty practice are learning on the job,' Kreider noted in her presentation. The Duke endocrine NP program is just one of two in the country that are housed within nursing schools. The other, at Mount Marty University in South Dakota, caters specifically to a rural population and includes pediatric endocrine training, which the Duke program currently does not. Two other programs, at Yale University School of Nursing and the University of California San Francisco, provide diabetes-specific training for NPs, embedded into their master's programs. When Duke's endocrine NP program began, the nursing school was already offering NPs training in orthopedics, cardiology, oncology, and HIV/AIDS. Initial funding for the endocrine program came from a 3-year grant from the Health Resources and Services Administration. About three quarters of the program's students are currently practicing/licensed NPs, while the rest are current Duke nursing students with NP majors. The training is divided into three parts: Advanced diabetes management (including hands-on diabetes technology training, recognition of diabetes types, insulin management, and inpatient management), general endocrinology (including thyroid, adrenal, pituitary, lipids, obesity, reproduction, gender medicine, and bone), and 168 hours of clinical rotations with a preceptor who is either an MD, physician assistant (PA), NP, or DO. The entire program can be completed in two or three semesters over 8-12 months. It is mostly distance-based, but during the summer, there is a 3-day onsite intensive with hands-on training. The program partners with Duke's Division of Endocrinology for guest lectures and preceptorships. 'Our physician endocrinologists have been wonderful. They are very supportive, and that has been very instrumental with both initiating and now flourishing later, as we continue,' Kreider said. There were a total of 167 graduates between 2016 and 2025, averaging about 18 per year. Most now practice in medically underserved areas. Kreider anticipates increasing that enrollment. 'We have interest from a private funding source. This might be on the horizon in the next year or so where we can really start to expand what we offer and the number of people that we can bring in.' Discussions are also underway to expand the number of similar programs for both NPs and PAs. 'We're going to need some really good partnerships with other academic medical centers to make that work,' she noted. Establishing board certification will also be important. 'If we're training people in standardized ways, how do we validate that knowledge? I think that will be a very valuable part of what we do and what we need to do,' Kreider commented. Ultimately, she predicted, 'Endocrine advanced practice providers will be the primary providers in the care of under-resourced and underprivileged patients, positioned as indispensable providers and team members across healthcare settings.' Kreider and Harris had no disclosures. Levine reported being a speaker for Ascendis Pharma and an advisory board member on one occasion for Madrigal Pharmaceuticals.
Medscape
21-05-2025
- Health
- Medscape
Palopegteriparatide Benefits Sustained in Hypoparathyroidism
ORLANDO, Fla. — After 2 years of treatment with the parathyroid hormone (PTH) analog palopegteriparatide (Yorvipath), adults with chronic hypoparathyroidism demonstrated continued improvement in renal function and skeletal dynamics, with no new safety issues identified. In hypoparathyroidism, low levels of PTH lead to hypocalcemia, hypercalciuria, and kidney damage, as well as reduced bone turnover and elevated fracture risk. Conventional treatment doesn't address the underlying defect and imposes a significant pill burden on patients, Lynn A. Kohlmeier, MD, director of endocrinology at Endocrinology and Spokane Osteoporosis, Spokane, Washington, explained at American Association of Clinical Endocrinology (AACE) Annual Meeting 2025. 'Conventional therapy for hypoparathyroidism consists of active D, prescription calcitriol, and multiple calcium supplements, which we know are really tough for our patients to take. It alleviates the hypocalcemic symptoms and hopefully keeps them from crashing and having laryngospasm or tetany or seizures. But if they're overtreated, or if they're dehydrated, the calcium could get too high and they can have renal concerns. The bottom line is this doesn't restore parathyroid hormone physiology,' Kohlmeier said. For PTH replacement therapy in hypoparathyroidism, 'we want something that provides PTH levels at a physiologic range to restore downstream calcitriol, active D production, promoting independence from conventional therapy, but…[also] normalizing serum calcium and urine calcium and phosphate, skeletal health, and quality of life. Palopegteriparatide is essentially that,' she explained. Palopegteriparatide, a once-daily injectable, was approved in the United States in August 2024 for the treatment of adults with hypoparathyroidism. That approval was based on the phase 3 randomized, double-blind, placebo-controlled PaTHway trial of 82 adults with hypoparathyroidism. In week 26 of this this study, 79% (48/61) vs just 5% (1/21) of patients randomized to palopegteriparatide vs placebo met the primary efficacy endpoint of achieving normal serum calcium levels without requiring conventional therapy (no active vitamin D and ≤ 600 mg/d calcium; P < .0001). The 26-week double-blind period was followed by a 182-week open-label period during which all participants were given palopegteriparatide, titrated to optimal dose. At week 104 (2 years), data were available for 76 of the original participants. Of that group, 97% (74/76) achieved independence from conventional therapy, with mean serum calcium and phosphate in the normal ranges. Independence from active vitamin D supplementation was achieved by 100% of the subjects, regardless of baseline kidney function. Asked to comment, endocrinologist Sean Ho Yoon, MD, assistant professor of medicine at the Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, told Medscape Medical News , 'This study, in the short term, proved that it is working. And the significance of this extension data is that even after 104 weeks, it still maintains the efficacy without complications.' Yoon also noted that the dosing did not appear to be a problem in the study, although Kohlmeier didn't present the titration details. 'Giving too much PTH can lead to too much bone turnover and high calcium in the body. But I think the study proved that as long as you're monitoring calcium regularly and titrating the dosage accordingly, that initial efficacy can be maintained while minimizing the complications.' At 2 years, independence from therapeutic doses of calcium was achieved by 95% (21/22) of participants with a baseline estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and 98% (53/54) of those with a baseline eGFR ≥ 60 mL/min/1.73 m2. Improvements in eGFR from baseline to week 104 occurred overall but were numerically greater in those with lower eGFR at baseline. Normalization of mean 24-hour urine calcium excretion was seen by week 26 in the treatment group, and reductions continued through week 104, from 393 mg/d at baseline to 151 mg/d in the 43 patients initially randomized to palopegteriparatide and from 330 mg/d to 183 mg/d in 14 from the placebo group who were switched to the drug after 26 weeks. (Normal urine calcium levels are ≤ 300 mg/d for men and ≤ 250 mg/d for women.) Mean levels of the bone turnover markers procollagen type 1 N-terminal propeptide and C-terminal telopeptide of type 1 collagen initially rose from baseline to week 26 with palopegteriparatide and then were maintained in the normal range at week 104, consistently in men, postmenopausal women, and premenopausal women. Mean bone mineral density T-scores and Z-scores declined from elevated baseline levels and stabilized within the normal range through week 104 across sex and menopausal status groups. Yoon said it was noteworthy that 'they were able to chemically prove with the bone markers that bone turnover is happening again with the PTH replacement. I'm curious, for the longer term, whether that actually helps reduce fractures. I think it's too premature to say that about the bone benefit, but it is promising that biochemically the bone turnover increased back to the age and sex-matched normal range.' Treatment-emergent adverse events (TEAEs) occurring in 5% or more of the 80 participants for whom data are available included injection site reactions (26.2%), hypercalcemia (13.8%), nausea (8.8%), headache (7.5%), hypocalcemia (7.5%), and postural orthostatic tachycardia syndrome (5.0%). Most TEAEs were mild or moderate and generally reported at similar rates across baseline eGFR groups, Kohlmeier said. The sole exception was the occurrence of TEAEs related to hyper- or hypocalcemia leading to an emergency or urgent care visit and/or hospitalization. These events were reported in 7.5% of patients overall, with four instances in the lower baseline eGFR group and two in the higher eGFR group. There was one death, a fatal cardiac arrest, not believed to be related to the drug. Overall, palopegteriparatide was associated with significant and sustained improvement in renal function and skeletal dynamics in adults with chronic hypoparathyroidism and was generally well-tolerated with no new safety signals identified, Kohlmeier concluded. The study was funded by Ascendis Pharma. Kohlmeier reported receiving research funding from Alexion/Amolyt and Ascendis Pharma, being on the speakers bureau and receiving honoraria from Amgen and Ascendis Pharma, and being a consultant/advisor for Alexion and Ascendis Pharma. Yoon had no disclosures.
Medscape
17-05-2025
- Health
- Medscape
Sotagliflozin Lowers A1c, Weight Even in Kidney Impairment
ORLANDO, Florida — Sotagliflozin (Inpefa) reduces A1c and body weight in people with type 2 diabetes, although the degree of improvement was attenuated in those with moderate-to-severe chronic kidney disease (CKD). "These findings highlight the importance of considering the effect of kidney function to help inform and tailor treatment decision-making for patients with diabetes and CKD," Belinda Hardin, PharmD, senior director of medical communications and head of field medical at Lexicon, said at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2025. Sotagliflozin, a novel agent that inhibits sodium-glucose cotransporter (SGLT) 1 as well as SGLT2, was approved by the US Food and Drug Administration (FDA) in 2023 for reducing the risks of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in patients with heart failure, and for preventing these same events in patients with type 2 diabetes, CKD, and other cardiovascular disease risk factors. The drug is not indicated for diabetes. In 2019, the FDA declined to approve sotagliflozin as adjunctive treatment for type 1 diabetes due to concerns about the increased risk for diabetic ketoacidosis. And in 2024, the agency again turned down Lexicon's application for sotagliflozin as a treatment for people with type 1 diabetes and CKD. The company hasn't sought an indication for sotagliflozin for type 2 diabetes. Two SGLT2 inhibitors, dapagliflozin (Farxiga) and empagliflozin (Jardiance), have indications for preventing heart failure hospitalizations in patients with heart failure as well as approvals for type 2 diabetes and preservation of renal function. The new findings, from a meta-analysis of eight double-blind, randomized, placebo-controlled trials, suggest that despite the lack of an indication for treatment of diabetes or obesity, sotagliflozin does result in A1c and body weight lowering across all levels of kidney function. This study is a companion to a previous similarly designed analysis showing that the effects of sotagliflozin on systolic blood pressure were maintained in patients with type 2 diabetes regardless of kidney function. Those findings were presented at the American Heart Association Scientific Session 2024, Hardin told Medscape Medical News . Asked for comment, session moderator Sara E. Lubitz, MD, associate professor of medicine and endocrine program director at Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, told Medscape Medical News : "This opens my mind more that if there is a heart failure patient with diabetes and we're looking for sugar reduction as well as heart failure protection, [sotagliflozin] is probably just as efficacious as the SGLT2 have the indication for glucose-lowering, but we're not pulling it out as a first-line [treatment]." All eight trials in the meta-analysis had similar designs and timeframes and were at least 26 weeks in duration. The patient-level intent-to-treat population data were pooled. Patients were divided into three subgroups based on kidney function: Subgroup 1: estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 (N = 2577) (N = 2577) Subgroup 2: eGFR ≥ 30 to < 60 mL/min/1.73m 2 (N = 1046) (N = 1046) Subgroup 3: eGFR < 30 mL/min/1.73m2 (N = 271) Mean patient ages were 60.2 years in subgroup 1, versus 69.3 and 67.1 years, respectively, in subgroups 2 and 3. The treatment groups were sotagliflozin 400 mg (N = 1728), sotagliflozin 200 mg (N = 728), or placebo (N = 1440). Overall, compared with placebo, A1c was significantly lowered with 200-mg sotagliflozin (less mean squares [LMS] difference, –0.33) and 400 mg (LMS difference, –0.48). Body weight was also reduced (LMS difference, –1.48 and –1.66, respectively). The effects on both A1c and body weight of both doses were statistically significant for the overall study population and subgroup 1 (normal kidney function). In subgroup 2, the effect on body weight remained significant for both doses, but only the 400-mg dose effect was significant for lowering A1c. The 400-mg dose produced significant reductions in all kidney function subgroups for both measures except A1c reduction in subgroup 3, although there was still benefit. Hardin told Medscape Medical News , "This provides us supplemental information with regard to heart failure outcomes, and not directly focusing on whether there's an additive benefit in terms of A1c or an additive lowering of A1c in patients with chronic kidney disease." Asked about future plans for sotagliflozin, she replied, "I don't think at this point you'll likely see sotagliflozin before the FDA for a glucose-lowering indication in type 2 patients. The file remains open for type 1 at the FDA, so that work continues." Hardin is an employee of Lexicon. Lubitz is a speaker for Ascendis and has received clinical trial research funding from Ascendis, Chiasma, and Takeda.
Medscape
16-05-2025
- Health
- Medscape
Fracture Risk Lower With Semaglutide vs Sleeve
Orlando, Fla. — Fracture risk in people treated for obesity appears significantly lower with semaglutide (Wegovy) vs sleeve gastrectomy, new data suggest. Previous animal studies have suggested a dose-dependent effect of glucagon like peptide 1 (GLP-1) receptor agonists on trabecular bone, including increased osteoblast activity, reduced apoptosis, and suppressed osteoclast activity. However, human data have been limited. A recent study utilizing a real-world electronic health record (EHR) database found that individuals with obesity who were treated with semaglutide experienced a significantly lower fracture risk — 26% less — compared with those who underwent bariatric surgery. The data were presented at American Association of Clinical Endocrinology (AACE) Annual Meeting 2025 by Jairo Noreña, MD, a second-year endocrinology fellow at Stanford University, Stanford, California. 'Considering weight loss per se is a risk factor for bone loss and microarchitecture impairment, we were excited to find a positive association with lower fracture risk favoring GLP-1 agonists. This correlation suggests that there are mechanisms that play a role reducing fracture risk in people using semaglutide. We were surprised by this finding, and it's an exciting correlation that warrants further study,' Noreña told Medscape Medical News . Clinically, he said, the data imply 'that patients…may benefit from a more favorable bone outcome [with semaglutide] compared to those who undergo sleeve gastrectomy for weight loss and should guide clinicians to favor this medication class in patients at higher risk of bone loss. We need further studies to help us understand this correlation, but so far with this data, most subjects with even average bone fracture risk will have a lower fracture risk when they use semaglutide vs undergoing sleeve gastrectomy.' Asked to comment, Session Moderator Sara E. Lubitz, MD, associate professor of medicine and endocrine program director at Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, told Medscape Medical News , 'We've known for a long time that bariatric surgery leads to decreased bone density. Is semaglutide really protective, or is it just a different degree of weight loss or a different patient population that we're using the semaglutide in? There are so many other variables.' Lubitz noted that the outcomes might differ between individuals with diabetes and those without, as well as among postmenopausal women. But she said that the findings 'at least give us more things that we need to look at in general about semaglutide and fractures compared to baseline populations.' Noreña noted, 'Diabetes itself may be a risk factor for osteoporosis, but semaglutide appears to play a protective role on bone health for obese individuals with or without diabetes during their weight loss journey.' The retrospective cohort analysis used the Eversana Life Sciences EHR dataset, representing more than 130 million patients seen at community hospitals and large practices in the Unites States from January 2016 to December 2023. The authors identified 92,405 adults with obesity and no prior history of fractures who were treated with semaglutide and 16,082 similar adults who had undergone sleeve gastrectomy, both within 1 year of obesity diagnosis. After high-dimensional propensity scoring, there were 2887 individuals in each treatment group. They had a mean age of 45 years, more than three quarters were women, and about half were White individuals. The semaglutide group had a higher prevalence of diabetes than the sleeve gastrectomy group, 40.2% vs 30.1%. Over an average 3-year follow-up, there were 86 fractures (3.0%) in the semaglutide group compared with 128 fractures (4.4%) in sleeve gastrectomy group (hazard ratio 0.74, 95% CI, 0.56-0.98). Noreña told Medscape Medical News , 'Some questions to address include whether these findings are independent of the class and could be observed in terzipatide or other GLP-1 agonists.' During his presentation, Noreña said that because surgical weight-loss interventions can affect nutrient absorption and reduce the absorption of both micro- and macronutrients, his group recently conducted a new retrospective analysis evaluating fracture outcome of semaglutide compared with oral medications such as phentermine/topiramate (Qsymia) and naltrexone/bupropion (Contrave). In this study, patients were matched based on their change in body mass index. Semaglutide significantly reduced the risk for any fracture by 25%. 'This reinforces the potential protective mechanism that other weight-loss modalities may lack,' Noreña said, adding that more detailed information will be presented at a later date. Noreña is the author of the book 'el poder del ayuno intermitente' in Spanish (the power of intermittent fasting) and received royalties from it. Lubitz is a speaker for Ascendis, and received clinical trials research funding from Ascendis, Chiasma, and Takeda.
Medscape
15-05-2025
- Health
- Medscape
New Data Back Crinecerfont in Congenital Adrenal Hyperplasia
Orlando, Florida — New data add to the evidence supporting use of crinecerfont for the treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, in both adults and children. The latest findings from the company's pediatric and adult phase 3 trials suggest that crinecerfont enables the dual goals of decreasing glucocorticoid dose to physiologic range while also reducing androgen excess. In adults, the drug leads to normalization of reproductive hormone levels at 1 year. The new data were presented at the 2025 annual meeting of the American Association of Clinical Endocrinology (AACE). In classic CAH, lack of the adrenal-specific enzyme 21-hydroxylase leads to deficient production of both cortisol and aldosterone production. The absence of endogenous cortisol results in increased secretion of corticotropin-releasing factor and adrenocorticotropic hormone (ACTH), which in turn drive excess production of adrenal androgens. Untreated, excess androgens can cause accelerated growth, early puberty, advanced bone maturation, and reduced stature in children. Adolescent girls can develop irregular menses, while testicular adrenal tumors can arise in boys. Both sexes can develop hypogonadism and/or impaired fertility in adulthood. Treatment involves use of glucocorticoids to replace the missing cortisol, but supraphysiologic doses have been typically required to also control the excess androgens. High glucocorticoid exposure can result in multiple adverse outcomes including reduced bone density, obesity, insulin resistance, type 2 diabetes, hyperlipidemia, and hypertension. In December 2024, the US Food and Drug Administration approved crinecerfont in combination with glucocorticoids in adults and pediatric patients aged 4 years and older with classic CAH. Crinecerfont is an oral, selective corticotropin-releasing factor type 1 receptor antagonist that acts in the pituitary to decrease adrenal androgens production independently of glucocorticoids. Approval was based on the results of two separate phase 3 trials, CAHtalyst Pediatric and CAHtalyst Adult. In both trials, the drug enabled more physiological glucocorticoid dosing. 'The point of crinecerfont is that by taking care of suppressing the ACTH and androgens, then the steroids can potentially be dosed at the level needed to replace the missing cortisol and not additionally to suppress the ACTH and androgens, because crinecerfont is doing that part for you,' adult study investigator Vivian H. Lin, MD, executive medical director, Neurocrine Biosciences, Inc., told Medscape Medical News . Asked to comment, David C. Lieb, MD, professor of medicine at Eastern Virginia Medical School, Norfolk, told Medscape Medical News that crinecerfont appears to be 'pretty impressive,' in that the mechanism of blocking ACTH release 'is like shutting off the system from above so you can just give people the steroids they need and not more. If you can lower the amount of glucocorticoid therapy that children and adolescents or adults need, that's fantastic, because presumably it's associated with reductions in cardiovascular risk and risk for fractures and all those other things, [including] growth issues in kids.' From an adult fertility standpoint, Lieb added, 'in the past, women with CAH were sort of under the impression that they couldn't have kids, or they may have even been told that they couldn't. But the truth is that with control of their disease, they can have children. You have to make sure that they're controlled and plan it out.' During pregnancy and delivery, 'you have to watch certain things, because they're adrenally insufficient. You have to be thoughtful about preparing them for that. But this is exciting because it may help women who otherwise might have difficulty controlling their androgen production to control it better, and maybe improve their ability to have children.' In Children, Most Achieved Androstenedione and/or Glucocorticoid Reduction The new pediatric data were presented at AACE by Patricia Y. Fechner, MD, medical director of the CAH program at Seattle Children's Hospital, and professor of pediatrics at the University of Washington School of Medicine, Seattle. In CAHtalyst Pediatric, a total of 103 children aged 4-17 years were randomized, 69 to crinecerfont and 34 to placebo. All but three remained in the trial at 28 weeks. Glucocorticoid doses were kept stable for 4 weeks and then reduced if possible based on androstenedione levels to reach a target glucocorticoid dose of 8-10 mg/m2/day while maintaining or improving androstenedione relative to baseline. Changes in glucocorticoid doses and morning androstenedione levels were analyzed using waterfall charts based on individual patient data at baseline and week 28. Overall, at 28 weeks, 90% of those in the crinecerfont group vs 21% in the placebo group achieved one or more thresholds for androstenedione reduction (≥ 30% from baseline or > 1.5x to 11mg/m2/day). At week 28, 30% (n = 20/67) in the crinecerfont group reached a physiologic glucocorticoid dose while maintaining or improving androstenedione levels vs none of the 31 with placebo. The drug was generally well tolerated. The most common adverse reactions were headache (25% vs 6% for placebo), abdominal pain (13% vs 0%), fatigue (7% vs 0%), nasal congestion (7% vs 3%) and epistaxis (4% vs 0%). There were no adrenal crises reported in the double-blind treatment period. The results demonstrate 'that clinicians can focus on reducing androgens, lowering glucocorticoid doses, or both, based on the individual patient's treatment goals,' Fechner concluded. In Adults, the Potential for Improved Fertility New data from the adult study were presented by Sonal Vaid, MD, a fellow at the National Institutes of Health Clinical Center, Bethesda, Maryland. At week 24 (the end of the double-blind, placebo-controlled trial period), a higher percentage of male participants who had abnormal hormonal levels (luteinizing hormone below the lower limit of normal or above the upper limit of normal, or androstenedione/testosterone ratio ≥ 0.5) at baseline had normalization of those levels with crinecerfont compared to placebo (47% vs 22% for luteinizing hormone and 19% vs 5% for the ratio), despite greater glucocorticoid dose decreases with crinecerfont. After week 24, there was an open-label period in which all participants received crinecerfont up to 1 year. During that time, there were further increases in the percentages of patients with normalization of luteinizing hormone (65%) and the androstenedione/testosterone ratio (24%), while glucocorticoid doses remained significantly reduced from baseline. At month 12, patients randomized to placebo who switched to crinecerfont during the open-label period experienced normalization of luteinizing hormone (44%) and androstenedione/testosterone (24%), despite significant glucocorticoid dose reductions over that period. The most common adverse reactions were fatigue (25% vs 15% for placebo), headache (16% vs 15%), dizziness (8% vs 3%), arthralgia (7% vs 0%), back pain (6% vs 3%), decreased appetite (4% vs 2%), and myalgia (4% vs 3%). 'Crinecerfont, a novel therapeutic option for reducing excess androgens and enabling the lowering of glucocorticoids to more physiologic doses, may also represent a promising approach to improving reproductive hormones in adults with CAH,' Vaid concluded. Both studies were funded by Neurocrine Biosciences, Inc. Lin is a company employee. Fechner has received research support from Neurocrine Biosciences, Spruce Biosciences, and Diurnal Ltd. (now Neurocrine UK Ltd.), has served as an advisory board participant and as a consultant for Neurocrine Biosciences, and as a consultant for Eton Pharmaceuticals. Vaid and Lieb have no disclosures.
