Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency

SAN DIEGO, Jan. 21, 2025 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced publication of a classic congenital adrenal hyperplasia (CAH)-focused supplement in The Journal of Clinical Endocrinology & Metabolism (JCEM), sponsored by the company. The supplement, titled "Challenges and Opportunities in the Management of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency Throughout the Lifetime," contains eight review articles that provide a comprehensive look at the clinical, psychosocial, treatment-related and day-to-day challenges faced by individuals with classic CAH. JCEM is a leader in disseminating research that supports healthcare providers, patients and caregivers in advancing the understanding and management of various endocrinology conditions, such as CAH. "Our understanding of the genetics, pathophysiology, and complications of CAH has exploded over the last 20 years," said Dr. Richard Auchus, M.D., Ph.D., Principal Investigator, Professor of Pharmacology and Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes at the University of Michigan. "These reviews capture the many dimensions of this complex condition and its management. The limitations of traditional glucocorticoid treatment, particularly in under-resourced areas, create a large disease burden, multiple co-morbidities, and poor outcomes for many patients. The authors are optimistic that this evolving knowledge and emerging treatments, such as corticotropin-releasing factor type 1 receptor antagonists, hold great promise for more personalized care, with improved androgen control and less glucocorticoid-related health consequences in patients." The JCEM supplement is a collection of reviews authored by leading endocrinologists and researchers and sponsored by Neurocrine Biosciences. It explores various aspects of classic CAH management, including pathophysiology, clinical manifestations, treatment challenges, barriers to care, psychosocial impact and advances in treatment, including CRENESSITY™ (crinecerfont), a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist. CRENESSITY is the first and only classic CAH treatment that directly reduces excess adrenocorticotropic hormone and downstream adrenal androgen production, allowing for glucocorticoid dose reduction. The articles aim to provide healthcare professionals with up-to-date insights and evidence-based approaches that can enhance clinical practice and patient care. "We are honored to support this important educational content in collaboration with The Journal of Clinical Endocrinology & Metabolism," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "Neurocrine is committed to empowering patients, caregivers and healthcare providers with the knowledge and support to navigate the life-long challenges of treating and living with CAH." The eight reviews include: Genetics and Pathophysiology of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency (Yang M and White PC) Clinical Manifestations and Treatment Challenges in Infants and Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency (Nokoff NJ, Buchanan C and Barker JM) Challenges in Adolescent and Adult Males with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency (Claahsen-van der Grinten HL, Adriaansen BPH and Falhammar H) Clinical Manifestations and Challenges in Adolescent and Adult Females with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency (Engberg H, Nordenstrӧm A and Hirschberg AL) Mental Health Issues Associated with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency, (Sandberg DE, Gardner M and Lapham ZK) Life With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: Challenges and Burdens (Witchel SF, Miller T, McCann E and Gupta A) Barriers to the Management of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency (Eitel KB and Fechner PY) Future Directions in the Management of Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency (Sarafoglou K and Auchus RJ) About Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia (CAH) is a rare genetic condition that results in an enzyme deficiency that alters the production of adrenal steroid hormones, such as cortisol, aldosterone and adrenal androgens, which are essential for life. Approximately 95% of CAH cases are caused by variants of the CYP21A2 gene that leads to deficiency of the enzyme 21-hydroxylase. Severe deficiency of this enzyme leads to an inability of the adrenal glands to produce enough cortisol and, in approximately 75% of cases, aldosterone. Because individuals with CAH are still able to produce androgens, the unused precursors that would normally be used to make cortisol instead result in the production of excess amounts of androgens. If left untreated, CAH can result in salt wasting, dehydration and even death. Historically, exogenous glucocorticoids (GCs) have been used not only to correct the endogenous cortisol deficiency, but doses used are higher than cortisol replacement needed (supraphysiologic) to lower the levels of adrenocorticotropic hormone (ACTH) and adrenal androgens. However, GC treatment at high doses has been associated with serious and significant complications of steroid excess, including metabolic issues such as weight gain and diabetes, cardiovascular disease and osteoporosis. Additionally, long-term treatment with high-dose GCs may have psychological and cognitive impact, such as changes in mood and memory. Adrenal androgen excess has been associated with abnormal bone growth and development in pediatric patients, female health problems such as excess facial hair growth and menstrual irregularities, testicular rest tumors in males and fertility issues in both sexes. About CRENESSITY™ (crinecerfont) CRENESSITY™ is a potent and selective, oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist developed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism for the treatment of classic congenital adrenal hyperplasia (CAH). Antagonism of CRF1 receptors in the pituitary has been shown to decrease ACTH levels, which in turn decreases the production of adrenal androgens and potentially the symptoms associated with CAH. The robust clinical study data demonstrate that lowering adrenal androgen levels with CRENESSITY enables lower, more physiologic dosing of GCs to replace missing cortisol. CRENESSITY comes in capsules and an oral solution. The capsule formulation is available in 50 mg and 100 mg doses. The oral solution is available as a 50 mg/mL strength formulation. For adults 18 years and older, the recommended dosage is 100 mg twice daily taken orally with a meal. For pediatric patients four to 17 years of age weighing less than 55 kg (121 lbs), the recommended dosage is based on body weight and is administered twice daily, taken orally with a meal. For pediatric patients weighing more than 55 kg (121 lbs), the recommended dosage is 100 mg twice daily taken orally with a meal. Healthcare providers can work with patients to determine the appropriate formulation for use depending on patient needs. Patients receiving CRENESSITY should continue GC therapy for cortisol replacement. Important Information Approved Uses CRENESSITY (crinecerfont) is a prescription medicine used together with glucocorticoids (steroids) to control androgen (testosterone-like hormone) levels in adults and children 4 years of age and older with classic congenital adrenal hyperplasia (CAH). IMPORTANT SAFETY INFORMATION Do not take CRENESSITY if you: Are allergic to crinecerfont, or any of the ingredients in CRENESSITY. CRENESSITY may cause serious side effects, including: Allergic Reactions. Symptoms of an allergic reaction include tightness of the throat, trouble breathing or swallowing, swelling of the lips, tongue, or face, and rash. If you have an allergic reaction to CRENESSITY, get emergency medical help right away and stop taking CRENESSITY. Risk of Sudden Adrenal Insufficiency or Adrenal Crisis With Too Little Glucocorticoid (Steroid) Medicine. Sudden adrenal insufficiency or adrenal crisis can happen in people with congenital adrenal hyperplasia who are not taking enough glucocorticoid (steroid) medicine. You should continue taking your glucocorticoid (steroid) medicine during treatment with CRENESSITY. Certain conditions such as infection, severe injury, or shock may increase your risk for sudden adrenal insufficiency or adrenal crisis. Tell your healthcare provider if you get a severe injury, infection, illness, or have planned surgery during treatment. Your healthcare provider may need to change your dose of glucocorticoid (steroid) medicine. Before taking CRENESSITY, tell your healthcare provider about all of your medical conditions, including if you are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of CRENESSITY in adults include tiredness, headache, dizziness, joint pain, back pain, decreased appetite, and muscle pain. The most common side effects of CRENESSITY in children include headache, stomach pain, tiredness, nasal congestion, and nose bleeds. These are not all the possible side effects of CRENESSITY. Call your healthcare provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at or call 1-800-FDA-1088. Dosage Forms and Strengths: CRENESSITY is available in 50 mg and 100 mg capsules and as an oral solution of 50 mg/mL. Please see full Prescribing Information. About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids,* as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (formerly Twitter) and Facebook. (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. CRENESSITY is a trademark of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from CRENESSITY. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of CRENESSITY, including the extent to which patients and physicians accept and adopt CRENESSITY; whether CRENESSITY receives adequate reimbursement from third-party payors; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; risks associated with the company's dependence on third parties for development and manufacturing activities related to CRENESSITY, and the ability of the company to manage these third parties; risks that additional regulatory submissions for CRENESSITY may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding CRENESSITY; risks that post-approval CRENESSITY commitments or requirements may be delayed; risks that CRENESSITY may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; and other risks described in the company's periodic reports filed with the Securities and Exchange Commission, including without limitation the company's quarterly report on Form 10-Q for the quarter ended September 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. © 2025 Neurocrine Biosciences, Inc. All Rights Reserved. CAP-CFT-US-0018 01/2025 SOURCE Neurocrine Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Substantial, Rapid and Sustained Statistically Significant Reductions of Key Biomarkers Achieved Across Doses, Including up to 80% Mean Reduction of Androstenedione Meaningful Improvements Demonstrated in Multiple Clinical Signs and Symptoms of CAH Affecting Patient Health Safety and Efficacy Data Support Initiation of Phase 3 Clinical Trial Management to Host Investor Conference Call Today at 8:30 AM ET SAN DIEGO, Jan. 10, 2025 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced positive topline results from an open-label, Phase 2 congenital adrenal hyperplasia (CAH) study of investigational atumelnant, a novel, once-daily oral adrenocorticotropic hormone (ACTH) receptor antagonist candidate being developed for the treatment of classic CAH and ACTH-dependent Cushing’s syndrome. “These exciting results show atumelnant not only lowered key biomarkers, but also had a significant impact on the signs and symptoms of CAH that are important to the overall health of people living with this condition,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “We are eager to move forward with a global Phase 3 pivotal trial for adults in CAH, as we simultaneously prepare to start a Phase 2b/3 trial in pediatric patients this year. Our internally discovered pipeline now has two drug candidates with positive later stage data, and we look forward to submitting INDs for four additional candidates now in first-in-human enabling studies, as we continue our strategy for building the premier global endocrine company.” “There has been a long-standing interest in using a potent, selective antagonist of the ACTH receptor for the treatment of CAH and other diseases of ACTH excess, leading to the design of atumelnant by Crinetics scientists,” said Dr. Alan Krasner, M.D., chief endocrinologist of Crinetics. “This Phase 2 study demonstrated that atumelnant was well tolerated and resulted in a reduction of adrenal androgen levels so rapid and robust that it allowed patients to realize meaningful improvements in long-term, pre-existing medical challenges, even within the short 12-week treatment period of this study.” Highlights from the Phase 2 TouCAHn TrialThe TouCAHn trial is an open-label, global, Phase 2 study designed to evaluate the efficacy, safety, and pharmacokinetics of atumelnant when administered for 12 weeks in people with CAH caused by 21-hydroxylase deficiency. The study enrolled 28 patients across 3 dose cohorts with classic CAH on a stable dose of glucocorticoid replacement. Primary endpoints included change from baseline in morning serum androstenedione (A4) levels and incidence of treatment-emergent adverse events. Change from baseline in morning serum 17-hydroxyprogesterone (17-OHP) was also evaluated as a secondary endpoint. Results For all doses, treatment with atumelnant resulted in rapid, substantial and sustained statistically significant reduction in A4 levels, the key biomarker for disease control (results in chart below). Primary Endpoint Atumelnant, Dosed Once DailyMean A4 Baseline*(ng/dL)A4 Change from Baseline at Week 12 (ng/dL)**40 mg (n=11) 1,213-619 (p=0.0003)80 mg (n=11)1,231-774 (p<0.0001)120 mg (n=6)1,064-954 (p<0.0001) *Morning serum levels **Least square mean change Additionally, rapid, substantial and sustained statistically significant reductions in 17-OHP, a confirmatory secondary biomarker of disease control, were achieved across doses. Treatment with atumelnant also had a significant impact on CAH signs and symptoms, including: Substantial reduction and normalization of testosterone in the majority of female participants (8/13),1 with 6 of the 11 impacted participants resuming mensesConsistent reduction in total adrenal volume observed across dose cohortsResolution of androgen mediated polycythemia in 5 of the 6 impacted participants Atumelnant has been generally well tolerated with no treatment-related severe or serious adverse events to date, irrespective of disease severity or dose level. No participants required dose reduction or discontinued from the trial. All adverse events to-date have been mild to moderate and generally transient. No consistent clinically important trends were observed across key safety parameters, including clinical safety laboratory values, physical examination, electrocardiogram or vital signs. The most common treatment-emergent adverse events included headache (7/28) and fatigue (5/28). Conference Call and WebcastCrinetics will host an investor conference call on January 10, 2025, at 8:30 am Eastern Time to discuss the topline results from this study. Following the live event, a replay will be available on the Investors section of the Company’s website. Dial-in Details:Domestic: 1-800-445-7795 International: 1-785-424-1699 Conference ID: CRNXQ4 Webcast: https://viavid.webcasts.com/starthere.jsp?ei=1703675&tp_key=d409cb44ff ABOUT ATUMELNANT Atumelnant, Crinetics’ second investigational compound, is the first once-daily, oral adrenocorticotropic hormone (ACTH) receptor antagonist that acts selectively at the melanocortin type 2 receptor (MC2R) on the adrenal gland. Diseases associated with excess ACTH can have significant impact on physical and mental health. Atumelnant has exhibited strong binding affinity for MC2R in preclinical models and has demonstrated suppression of adrenally derived glucocorticoids and androgens that are under the control of ACTH. Data from a 12-week Phase 2 study demonstrated compelling treatment benefits of atumelnant, evidenced by the rapid, substantial and sustained statistically significant reductions in key CAH disease related biomarkers, including androstenedione and 17-hydroxyprogesterone, in a diverse population. Atumelnant is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome. For more information about the Phase 2 TouCAHn study in classic CAH, please visit clinicaltrials.gov (NCT05907291). ABOUT CRINETICS PHARMACEUTICALS Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Crinetics’ lead development candidate, paltusotine, is the first investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist that is in clinical development for acromegaly and carcinoid syndrome associated with neuroendocrine tumors. Atumelnant is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome. All of the company’s drug candidates are orally delivered, small molecule, new chemical entities resulting from in-house drug discovery efforts, including additional discovery programs addressing a variety of endocrine conditions such as hyperparathyroidism, polycystic kidney disease, Graves’ disease (including thyroid eye disease), diabetes, obesity and GPCR-targeted oncology indications. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of atumelnant, including the therapeutic potential and clinical benefits or safety profile thereof; the expected timing of additional data and topline results from studies of atumelnant in CAH and ACTH-dependent Cushing’s syndrome; the expected timing and initiation of Phase 3 studies of atumelnant in CAH; the therapeutic potential and clinical benefits or safety profile of paltusotine; and the future development and focus of Crinetics. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential,” “upcoming” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including, without limitation, initial or topline data that we report may change following completion or a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, and the FDA and other regulatory authorities may not agree with our interpretation of such results; unexpected adverse side effects or inadequate efficacy of the company’s product candidates that may limit their development, regulatory approval and/or commercialization; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development or be approved for marketing; and the other risks and uncertainties described in the company’s periodic filings with the Securities and Exchange Commission (SEC). The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2023 and its Quarterly report on Form 10-Q for the quarter ended March 31, 2024, June 30, 2024, and September 30, 2024. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: Investors: Gayathri Diwakar Head of Investor Relations gdiwakar@crinetics.com (858) 345-6340 Media: Natalie Badillo Head of Corporate Communications nbadillo@crinetics.com (858) 345-6075  1 Sample size includes female participants not on hormonal contraceptives with intact uterus. Those with restored menses following atumelnant treatment included three previously amenorrheic participants and three with previously irregular menses.

PITTSBURGH, Dec. 23, 2024 /PRNewswire/ -- PANTHERx® Rare, a leader in rare disease product patient access and support services in the United States, is pleased to announce that it was selected by Neurocrine Biosciences, Inc. for the distribution of CRENESSITY™ (crinecerfont), an oral selective corticotropin-releasing factor type 1 (CRF1) receptor antagonist indicated to improve androgen control and enable a reduced glucocorticoid dose in patients 4 years of age and older with classic congenital adrenal hyperplasia (CAH). CRENESSITY is the first non-steroidal treatment approved for classic CAH and a first-in-class therapy that provides a novel approach to treatment for this rare disorder. CAH is a rare, autosomal recessive genetic disorder that results from deficiency of one of the enzymes needed for adrenal hormone production. The most common cause of CAH is 21-hydroxylase (21-OHD) deficiency, which accounts for approximately 95% of cases.2 21-OHD deficiency prevents the body from producing cortisol, which is essential to respond to stress and illness. In about 75% of cases, aldosterone production is also affected, which impairs the body's ability to regulate salt and water levels, and thereby blood pressure.2,3 In response to low levels of cortisol and aldosterone, the hypothalamus-pituitary-adrenal (HPA) axis is activated, leading to overproduction of androgens.2 Excess androgen production can cause a variety of symptoms, including anxiety, acne, hirsutism, atypical genital development in affected females, fertility issues, early-onset puberty, and rapid growth followed by premature completion resulting in short stature.3 These symptoms can significantly impact both the physical and mental health of those affected with CAH. "We are proud to partner with Neurocrine Biosciences for the distribution of CRENESSITY. This collaboration underscores PANTHERx's dedication to providing personalized care and seamless access to transformative therapies for patients with rare and complex conditions," said Rob Snyder, Executive Chair, PANTHERx® Rare Pharmacy. About PANTHERx Rare PANTHERx Rare is a dual-accredited specialty pharmacy focused on rare and orphan disease, distributing several orphan products and providing access and support services to those needing them most. PANTHERx transforms lives by delivering medicine breakthroughs, clinical excellence, and access solutions to people living with rare and devastating conditions. While each rare condition affects few people, together all rare diseases impact an estimated 25 to 30 million Americans.3 Currently over 7,000 rare diseases have been identified and more than 90% of rare diseases are still without an FDA-approved treatment. 3 Changes in federal policy and advances in science have led to a surge in FDA orphan drug approvals, providing tremendous hope to the rare disease community. PANTHERx is a dual-accredited specialty pharmacy, holding distinctions in rare disease including the Accreditation Commission for Health Care (ACHC) Distinction in Orphan Drugs and Utilization Review Accreditation Commission (URAC) Rare Disease Center of Excellence. As a pharmacy focused on patient satisfaction, PANTHERx is now a six-time winner of the prestigious MMIT Patient Choice Award, including the 2023 honor. PANTHERx is headquartered in Pittsburgh, Pennsylvania and is licensed in all 50 states and US territories. 1. CRENESSITY™ (crinecerfont) [package insert]. Neurocrine Biosciences, Inc. 2024. 2. Congenital Adrenal Hyperplasia (CAH). Neurocrine Biosciences, Inc. Accessed October 21, 2024. 3. Congenital Adrenal Hyperplasia. NORD (National Organization for Rare Disorders). Published June 8, 2023. Accessed October 21, 2024. For more information, please contact [email protected] SOURCE PANTHERx Rare Pharmacy WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED