Last update 17 Dec 2024

Crinecerfont

Last update 17 Dec 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine, Crinecerfont Hydrochloride, NBI-74788

+ [4]

Target

CRHR1

Mechanism

CRHR1 antagonists(Corticotropin-releasing factor receptor 1 antagonists)

Therapeutic Areas

Congenital DisordersEndocrinology and Metabolic DiseaseUrogenital Diseases+ [1]

Active Indication

Classic Congenital Adrenal HyperplasiaCongenital Adrenal Hyperplasia Due to 21 Hydroxylase DeficiencyAdrenal Hyperplasia, Congenital

Inactive Indication

Depressive Disorder, Major

Originator Organization

Sanofi

Active Organization

Neurocrine Biosciences, Inc.

Inactive Organization

Sanofi SA

Drug Highest PhaseApproved

First Approval Date

US (13 Dec 2024),

Classic Congenital Adrenal Hyperplasia

RegulationPriority Review (US), Fast Track (US), Rare Pediatric Disease (US), Orphan Drug (EU), Breakthrough Therapy (US), Orphan Drug (US)

Structure

Molecular FormulaC27H29Cl2FN2OS

InChIKeyBMXALUHUEGRRCH-JIDHJSLPSA-N

CAS Registry321839-75-2

Clinical Trials associated with Crinecerfont

NCT04806451 / Active, not recruitingPhase 3

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Crinecerfont (NBI-74788) in Pediatric Subjects With Classic Congenital Adrenal Hyperplasia, Followed by Open-Label Treatment

This is a Phase 3 study to evaluate the efficacy, safety, and tolerability of crinecerfont versus placebo administered for 28 weeks in approximately 81 pediatric participants with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The study consists of a 28-week double blind, placebo-controlled period, followed by 24 weeks of open-label treatment with crinecerfont. Subsequently, participants may elect to participate in the open-label extension (OLE) period. The duration of participation in the study is approximately 14 months for the core study and will be a variable amount of time per participant for the OLE (estimated to be approximately 3 years).

Start Date25 Jun 2021

Sponsor / Collaborator

Neurocrine Biosciences, Inc.

NCT04490915 / Active, not recruitingPhase 3

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Crinecerfont (NBI-74788) in Adult Subjects With Classic Congenital Adrenal Hyperplasia, Followed by Open-Label Treatment

This is a Phase 3 study to evaluate the efficacy, safety, and tolerability of crinecerfont versus placebo administered for 24 weeks in approximately 165 adult participants with classic CAH due to 21-hydroxylase deficiency. The study consists of a 6-month randomized, double-blind, placebo-controlled period, followed by 1 year of open-label treatment with crinecerfont. Subsequently, participants may elect to participate in the open-label extension (OLE) period. The duration of participation in the study is approximately 20 months for the core study and will be a variable amount of time per subject for the OLE (estimated to be approximately 3 years).

Start Date16 Nov 2020

Sponsor / Collaborator

Neurocrine Biosciences, Inc.

NCT04045145 / CompletedPhase 2

A Phase 2, Open-Label, Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Pediatric Subjects With Congenital Adrenal Hyperplasia

This is a Phase 2, open-label, multiple-dose, study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NBI-74788 (crinecerfont) in pediatric participants (14 to 17 years of age) with a documented medical diagnosis of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH).

Start Date12 Dec 2019

Sponsor / Collaborator

Neurocrine Biosciences, Inc.

100 Clinical Results associated with Crinecerfont

100 Translational Medicine associated with Crinecerfont

100 Patents (Medical) associated with Crinecerfont

Literatures (Medical) associated with Crinecerfont

24 Oct 2024·NEW ENGLAND JOURNAL OF MEDICINE

Crinecerfont in Adult Congenital Adrenal Hyperplasia

Letter

Author: Auchus, Richard J ; Lin, Vivian H ; Sturgeon, Julia

08 Aug 2024·NEW ENGLAND JOURNAL OF MEDICINE

Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia

Article

Author: Falhammar, Henrik ; Sarafoglou, Kyriakie ; Russo, Gianni ; Auchus, Richard J ; Lin, Vivian H ; Witchel, Selma F ; Hamidi, Oksana ; Roberts, Eiry ; Rodien, Patrice ; Srirangalingam, Umasuthan ; Cutler, Gordon B ; Sturgeon, Julia ; Pivonello, Rosario ; Farber, Robert H ; Reisch, Nicole ; Bancos, Irina ; Merke, Deborah P ; Kiefer, Florian W ; Chan, Jean L ; Isidori, Andrea M

BACKGROUND:

Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control of adrenal-derived androgen excess usually requires supraphysiologic glucocorticoid dosing, which predisposes patients to glucocorticoid-related complications. Crinecerfont, an oral corticotropin-releasing factor type 1 receptor antagonist, lowered androstenedione levels in phase 2 trials involving patients with CAH.

METHODS:

In this phase 3 trial, we randomly assigned adults with CAH in a 2:1 ratio to receive crinecerfont or placebo for 24 weeks. Glucocorticoid treatment was maintained at a stable level for 4 weeks to evaluate androstenedione values, followed by glucocorticoid dose reduction and optimization over 20 weeks to achieve the lowest glucocorticoid dose that maintained androstenedione control (≤120% of the baseline value or within the reference range). The primary efficacy end point was the percent change in the daily glucocorticoid dose from baseline to week 24 with maintenance of androstenedione control.

RESULTS:

All 182 patients who underwent randomization (122 to the crinecerfont group and 60 to the placebo group) were included in the 24-week analysis, with imputation of missing values; 176 patients (97%) remained in the trial at week 24. The mean glucocorticoid dose at baseline was 17.6 mg per square meter of body-surface area per day of hydrocortisone equivalents; the mean androstenedione level was elevated at 620 ng per deciliter. At week 24, the change in the glucocorticoid dose (with androstenedione control) was -27.3% in the crinecerfont group and -10.3% in the placebo group (least-squares mean difference, -17.0 percentage points; P<0.001). A physiologic glucocorticoid dose (with androstenedione control) was reported in 63% of the patients in the crinecerfont group and in 18% in the placebo group (P<0.001). At week 4, androstenedione levels decreased with crinecerfont (-299 ng per deciliter) but increased with placebo (45.5 ng per deciliter) (least-squares mean difference, -345 ng per deciliter; P<0.001). Fatigue and headache were the most common adverse events in the two trial groups.

CONCLUSIONS:

Among patients with CAH, the use of crinecerfont resulted in a greater decrease from baseline in the mean daily glucocorticoid dose, including a reduction to the physiologic range, than placebo following evaluation of adrenal androgen levels. (Funded by Neurocrine Biosciences; CAHtalyst ClinicalTrials.gov number, NCT04490915.).

08 Aug 2024·NEW ENGLAND JOURNAL OF MEDICINE

Phase 3 Trial of Crinecerfont in Pediatric Congenital Adrenal Hyperplasia

Article

Author: Martinerie, Laetitia ; Speiser, Phyllis W ; Nokoff, Natalie J ; Kim, Mimi S ; Chan, Jean L ; Rosales, Gelliza B G ; Sarafoglou, Kyriakie ; Fechner, Patricia Y ; Lodish, Maya ; Roberts, Eiry ; Farber, Robert H ; Vogiatzi, Maria G ; Auchus, Richard J ; Clemente, María ; Felner, Eric I ; Jeha, George S

BACKGROUND:

Children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency require treatment with glucocorticoids, usually at supraphysiologic doses, to address cortisol insufficiency and reduce excess adrenal androgens. However, such treatment confers a predisposition to glucocorticoid-related complications. In 2-week phase 2 trials, patients with CAH who received crinecerfont, a new oral corticotropin-releasing factor type 1 receptor antagonist, had decreases in androstenedione levels.

METHODS:

In this phase 3, multinational, randomized trial, we assigned pediatric participants with CAH, in a 2:1 ratio, to receive crinecerfont or placebo for 28 weeks. A stable glucocorticoid dose was maintained for 4 weeks, and the dose was then adjusted to a target of 8.0 to 10.0 mg per square meter of body-surface area per day (hydrocortisone dose equivalents), provided that the androstenedione level was controlled (≤120% of the baseline level or within the reference range). The primary efficacy end point was the change in the androstenedione level from baseline to week 4. A key secondary end point was the percent change in the glucocorticoid dose from baseline to week 28 while androstenedione control was maintained.

RESULTS:

A total of 103 participants underwent randomization, of whom 69 were assigned to crinecerfont and 34 to placebo; 100 (97%) remained in the trial at 28 weeks. At baseline, the mean glucocorticoid dose was 16.4 mg per square meter per day, and the mean androstenedione level was 431 ng per deciliter (15.0 nmol/liter). At week 4, androstenedione was substantially reduced in the crinecerfont group (-197 ng per deciliter [-6.9 nmol/liter]) but increased in the placebo group (71 ng per deciliter [2.5 nmol/liter]) (least-squares mean difference [LSMD], -268 ng per deciliter [-9.3 nmol/liter]; P<0.001); the observed mean androstenedione value, obtained before the morning glucocorticoid dose, was 208 ng per deciliter (7.3 nmol/liter) in the crinecerfont group, as compared with 545 ng per deciliter (19.0 nmol/liter) in the placebo group. At week 28, the mean glucocorticoid dose had decreased (while androstenedione control was maintained) by 18.0% with crinecerfont but increased by 5.6% with placebo (LSMD, -23.5 percentage points; P<0.001). Headache, pyrexia, and vomiting were the most common adverse events.

CONCLUSIONS:

In this phase 3 trial, crinecerfont was superior to placebo in reducing elevated androstenedione levels in pediatric participants with CAH and was also associated with a decrease in the glucocorticoid dose from supraphysiologic to physiologic levels while androstenedione control was maintained. (Funded by Neurocrine Biosciences; CAHtalyst Pediatric ClinicalTrials.gov number, NCT04806451.).

News (Medical) associated with Crinecerfont

30 Sep 2024

·www.prnewswire.com

Neurocrine Biosciences's Crinecerfont is Set to Transform the Congenital Adrenal Hyperplasia Treatment Market | DelveInsight

Neurocrine Biosciences has announced that the US Food and Drug Administration (FDA) has accepted its two New Drug Applications (NDA) for crinecerfont, granting them Priority Review designations. The applications cover the treatment of children, adolescents, and adults with classic congenital adrenal hyperplasia (CAH). If approved, crinecerfont would represent the first new treatment for CAH in 70 years and the first-in-class therapy offering a novel mechanism of action to address this rare and serious endocrine disorder. LAS VEGAS, Sept. 30, 2024 /PRNewswire/ -- CAH refers to a rare set of inherited autosomal recessive disorders that impair hormone production in the adrenal glands, which sit on top of the kidneys. Normally, these glands produce three types of hormones: corticosteroids, mineralocorticoids, and androgens. CAH is mostly caused by mutations in the 21-hydroxylase gene, which accounts for more than 90% of cases. In rare instances, mutations in the 11-hydroxylase gene can also lead to CAH. In the 7MM, the US accounted for the highest prevalent cases of congenital adrenal hyperplasia in 2023, with around 50% of the total prevalent cases across the 7MM; these numbers are expected to increase during the forecast period (2024–2034). DelveInsight's analysis reveals that a higher prevalence of diagnosed congenital adrenal hyperplasia is observed in the 18-year-old and above age group across the 7MM. Among mutation-based congenital adrenal hyperplasia cases, 21 OHD (CYP21A2 gene mutation) represents a higher prevalence compared to 11-Beta hydroxylase (CYP11B1 gene mutation), and others. The approach to managing CAH differs significantly based on its type and severity. While CAH cannot be completely cured, it can be managed effectively. For classical CAH, treatment begins shortly after birth and continues throughout the individual's life. Those with classical CAH should work with a team of healthcare professionals, including experts in pediatric endocrinology, uro-gynecologic surgery, psychology, and genetics. With appropriate care, individuals with classical CAH can lead normal and satisfying lives. In contrast, treatment for non-classical CAH may not be necessary, depending on the severity of symptoms. The management of classic CAH focuses on three main objectives: correcting adrenal insufficiency, lowering adrenal androgens to appropriate levels, and preventing iatrogenic hypercortisolism. Hydrocortisone is the primary glucocorticoid used, administered two to three times daily with higher doses in the morning and lower doses in the evening to align with the body's natural circadian rhythm. For NC-CAH, cortisol replacement is generally unnecessary, except in specific situations such as adult women with hyperandrogenism and fertility problems, or pediatric patients experiencing rapidly advancing precocious puberty. Currently, the only medication approved in Europe for CAH treatment is EFMODY (Hydrocortisone Modified-release Hard Capsules) by Neurocrine Biosciences. Learn more about the FDA-approved congenital adrenal hyperplasia drugs @ Drugs for Congenital Adrenal Hyperplasia Treatment EFMODY replicates the natural circadian rhythm of cortisol secretion. It compensates for low cortisol levels in patients with congenital adrenal hyperplasia, aiding in the management of the condition's symptoms. Approved for use in adolescents aged 12 and older, as well as adults, EFMODY uses hydrocortisone—a glucocorticoid that affects various tissues through intracellular steroid receptors. Containing synthetic cortisol, EFMODY gradually releases it in the intestines to mimic the body's natural cortisol release, helping to restore hormone balance and alleviate condition-related issues. In May 2021, the EMA approved EFMODY for treating congenital adrenal hyperplasia in patients aged 12 and above. Diurnal launched the drug in Germany and Austria in September 2021, and later in the United Kingdom. In November 2022, Neurocrine Biosciences acquired Diurnal for approximately USD 55 million. To know more about congenital adrenal hyperplasia treatment options, visit @ New Treatment for Congenital Adrenal Hyperplasia The congenital adrenal hyperplasia pipeline is strong with many companies working in the domain. Various potential therapies that are projected to enter during the forecast period include Neurocrine Biosciences' Crinecerfont, Spruce Biosciences' Tildacerfont (SPR001), Crinetics Pharmaceuticals' Atumelnant (CRN04894), BridgeBio's BBP-631, Lundbeck's Lu AG13909, and others. Discover which therapies are expected to grab major congenital adrenal hyperplasia market share @ Congenital Adrenal Hyperplasia Market Report Crinecerfont is an investigational oral medication that acts as a selective antagonist for the corticotropin-releasing factor Type 1 receptor (CRF1). It's being developed to manage and regulate high levels of Adrenocorticotropic Hormone (ACTH) and adrenal androgens without relying on glucocorticoids, specifically for treating congenital adrenal hyperplasia caused by 21-hydroxylase deficiency. By blocking the CRF1 receptor, Crinecerfont reduces the overproduction of ACTH, which in turn decreases the excess production of androgens seen in CAH patients. This mechanism aims to normalize hormone levels and address the root cause of the condition. In July 2024, Neurocrine Biosciences announced that the FDA has accepted its two New Drug Applications (NDAs) for crinecerfont, both with Priority Review designations. These applications are for treating classic congenital adrenal hyperplasia in children, adolescents, and adults. If approved, crinecerfont would become the first new treatment for CAH in 70 years and a pioneering therapy with a novel approach for this rare endocrine disorder. The NDAs for crinecerfont include (1) a capsule formulation (NDA# 218808) and (2) an oral solution formulation (NDA# 218820), both addressing the efficacy and safety of crinecerfont for classic CAH. The FDA has set Prescription Drug User Fee Act (PDUFA) target action dates for these applications as December 29 and December 30, 2024, respectively. The FDA has indicated it does not plan to hold an advisory committee meeting regarding these NDAs. Crinecerfont received an Orphan Drug designation (ODD) in March 2019 and a Breakthrough Therapy designation (BTD) in December 2023. The results from the CAHtalyst Phase III trial, involving both pediatric and adult patients with CAH caused by 21-OHD, were published online in The New England Journal of Medicine on June 2 and June 1, respectively, and were also presented at ENDO 2024. BBP-631 is a gene therapy in development using adeno-associated virus (AAV) to target the root cause of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. This therapy aims to deliver a functional copy of the 21-hydroxylase gene directly to the adrenal glands, where hormones are produced. Animal studies have demonstrated its effectiveness in providing consistent and long-term delivery to the adrenal glands. If successful, BBP-631 could help restore natural hormone and steroid levels in people with CAH, allowing them to produce cortisol and aldosterone—something no current treatments or clinical trials can achieve. BridgeBio envisions this gene therapy as a potential solution to correct the hormonal imbalance caused by CAH. Tildacerfont is a new-generation antagonist targeting the Corticotropin-releasing factor (CRF1) receptor. It aims to significantly enhance disease management and decrease reliance on steroids for patients with classic congenital adrenal hyperplasia and other conditions associated with high ACTH levels. By binding to CRF1 receptors, tildacerfont reduces the overproduction of ACTH and, consequently, lowers the production of adrenal androgens like androstenedione in patients with CAH and Polycystic Ovary Syndrome (PCOS). In August 2024, Spruce Biosciences announced that the top-line results from the CAHmelia-204 study, which evaluates tildacerfont in adult CAH patients, and the CAHptain-205 study, which assesses the drug in both adult and pediatric CAH patients, are expected to be released in the fourth quarter of 2024. Discover more about drugs for congenital adrenal hyperplasia in development @ Congenital Adrenal Hyperplasia Clinical Trials The anticipated launch of these emerging therapies for congenital adrenal hyperplasia are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the congenital adrenal hyperplasia market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for congenital adrenal hyperplasia is expected to grow from USD 20 billion in 2023 with a tremendous CAGR of ~40% by 2034. This growth can be attributed to the introduction of upcoming therapies and the rising prevalence of the disease. DelveInsight's latest published market report titled as Congenital Adrenal Hyperplasia Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the congenital adrenal hyperplasia country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The congenital adrenal hyperplasia market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of Congenital Adrenal Hyperplasia Gender-specific Cases of Congenital Adrenal Hyperplasia Age-specific Cases of Congenital Adrenal Hyperplasia Mutation-based Cases of Congenital Adrenal Hyperplasia Type-specific Cases of Congenital Adrenal Hyperplasia The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM congenital adrenal hyperplasia market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis up to 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this congenital adrenal hyperplasia market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the congenital adrenal hyperplasia market. Also, stay abreast of the mitigating factors to improve your market position in the congenital adrenal hyperplasia therapeutic space. Related Reports Congenital Adrenal Hyperplasia Pipeline Congenital Adrenal Hyperplasia Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key CAH companies, including Spruce Biosciences, Lundbeck, among others. Congenital Adrenal Hyperplasia Epidemiology Forecast Congenital Adrenal Hyperplasia Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and CAH epidemiology trends. Adrenal Crisis Market Adrenal Crisis Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key adrenal crisis companies including Eton Pharmaceuticals, Antares Pharma , among others. Adrenal Crisis Pipeline Adrenal Crisis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key adrenal crisis companies, including Eton Pharmaceuticals, Antares Pharma, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Drug ApprovalBreakthrough TherapyPriority Review

01 Aug 2024

·www.prnewswire.com

Neurocrine Biosciences Reports Second Quarter 2024 Financial Results and Raises 2024 INGREZZA Sales Guidance

INGREZZA® (valbenazine) Second Quarter Net Product Sales of $580 Million Representing 32% Year-Over-Year Growth INGREZZA ® (valbenazine) 2024 Net Product Sales Guidance Raised to $2.25 - $2.3 Billion Top-Line Phase 2 Data Readouts for NBI-'568 and Luvadaxistat Remain On Track in Q3 SAN DIEGO, Aug. 1, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced its financial results for the second quarter ended June 30, 2024 and provided an update on its 2024 financial guidance. "At Neurocrine, we are energized by the tremendous opportunity we see to help many more patients, and we are encouraged by our recent progress, including INGREZZA's continued success in treating tardive dyskinesia and Huntington's disease chorea and the FDA's decision to grant Priority Review for crinecerfont to treat congenital adrenal hyperplasia," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "We are in the process of building our endocrinology team and expanding the INGREZZA salesforce, positioning our company for continued strong growth in the years ahead." Kevin Gorman added, "As I look ahead to my planned retirement in October, I have never been more confident in Neurocrine's future. I am incredibly proud of all that we have achieved together and excited to see what this team will continue to accomplish for patients under Kyle Gano's leadership." Financial Highlights INGREZZA Net Product Sales Highlights INGREZZA second quarter 2024 net product sales were $580 million and grew 32% compared to the second quarter 2023 Year-over-year growth driven by strong underlying patient demand and improvement in gross-to-net dynamics Other Key Financial Highlights Differences in second quarter 2024 GAAP and Non-GAAP operating expenses compared with second quarter 2023 were driven by: Increased R&D expense in support of an expanded and advancing clinical portfolio including investments in muscarinic compounds, gene therapy programs and second generation VMAT2 inhibitors. R&D expense for the second quarter 2024 includes $27 million for development milestones achieved under our collaborations with Nxera Pharma UK Limited (Nxera, formerly known as Sosei Heptares), Takeda Pharmaceutical Company Limited (Takeda) and Voyager Therapeutics, Inc. (Voyager) Increased SG&A expense includes incremental investment in crinecerfont-related headcount, crinecerfont-related pre-launch activities, and continued investment in INGREZZA. GAAP SG&A expense also includes impairment charges of $14 million associated with leased office space that has been vacated as we continue to occupy our new campus facility Second quarter 2024 GAAP net income and earnings per share were $65 million and $0.63, respectively, compared with $96 million and $0.95, respectively, for second quarter 2023 Second quarter 2024 Non-GAAP net income and earnings per share were $169 million and $1.63, respectively, compared with $126 million and $1.25, respectively, for second quarter 2023 Differences in second quarter 2024 GAAP and Non-GAAP net income compared with second quarter 2023 driven by: Higher INGREZZA net sales and improved operating margin Second quarter 2024 includes $50 million charge associated with the settlement of convertible senior notes conversions (Non-GAAP adjustment) Second quarter 2024 includes $20 million loss from changes in fair value of equity security investments compared to $37 million gain the second quarter 2023 (Non-GAAP adjustment) Second quarter 2024 includes $27 million of development milestones expense achieved under collaborations Second quarter 2024 includes $14 million leased office space impairment charge (Non-GAAP adjustment) At June 30, 2024, the Company had cash, cash equivalents and marketable securities totaling approximately $1.7 billion which reflects the $309 million payment to fully retire our convertible senior notes A reconciliation of GAAP to Non-GAAP financial results can be found in Table 3 and Table 4 at the end of this news release. Recent Developments Announced Kevin Gorman, Ph.D., will retire as Chief Executive Officer on October 11, 2024. Kyle Gano, Ph.D., currently Neurocrine's Chief Business Development and Strategy Officer, will succeed him in the CEO role. Dr. Gano will also join the Company's Board of Directors at that time, and Dr. Gorman will continue to serve on the Company's Board. Announced positive topline data for the Phase 2 SAVITRI™ study. This randomized, double-blind, placebo-controlled dose-finding study assessed the efficacy and safety of NBI-1065845 in adult subjects with major depressive disorder (MDD). NBI-1065845 is an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development as a potential treatment for patients with MDD who have not benefited from treatment with at least one antidepressant in their current episode of depression. Announced FDA accepted New Drug Applications (NDAs) and granted Priority Review for crinecerfont for adult and pediatric patients with congenital adrenal hyperplasia (CAH). The agency set Prescription Drug User Fee (PDUFA) target actions dates of December 29, 2024 for the capsule formulation and December 30, 2024 for the oral solution formulation. At the Endocrine Society Annual Meeting (ENDO 2024), presented new Phase 3 clinical study data from the CAHtalyst™ registrational studies of crinecerfont in pediatric and adult patients with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. In parallel, announced that the primary study results from the CAHtalyst™ registrational studies of crinecerfont in pediatric and adult patients with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have been published in The New England Journal of Medicine. Initiated Phase 2 study of NBI-1070770 in adults with major depressive disorder. NBI-1070770 is a novel, selective and orally active, negative allosteric modulator (NAM) of the NR2B subunit-containing N-methyl-D-aspartate (NMDA NR2B) receptor. Initiated Phase 1 study of NBI-1117567 in healthy adult participants. NBI-1117567 is an investigational, oral, M1/M4 (M1 preferring) selective muscarinic agonist for the potential treatment of neurological and neuropsychiatric conditions. Initiated Phase 1 study of NBI-1076968 in healthy adult participants. NBI-1076968 is an investigational, oral, M4 subtype-selective muscarinic antagonist for the potential treatment of movement disorders. Received notification from the Centers for Medicare and Medicaid Services that INGREZZA qualified for the Specified Small Manufacturer Exception pertaining to the Part D redesign of the Inflation Reduction Act. Settled the convertible senior notes due May 15, 2024 in full in cash upon maturity. Announced planned expansion of the INGREZZA psychiatry and long-term care sales teams to better serve patients by accelerating the number of people who are diagnosed and treated for tardive dyskinesia and chorea associated with Huntington's disease. Launched new sprinkle formulation of INGREZZA® (valbenazine) capsules for the treatment of adults with tardive dyskinesia and chorea associated with Huntington's disease. Raised 2024 Net Sales Guidance and Updated Expense Guidance 2024 Pipeline Milestones and Key Activities Key: AMPA = alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; CFR1 = Corticotropin-Releasing Factor Type 1; M4 = M4 Muscarinic Receptor; DAAO = d-amino acid oxidase; NMDA NR2B NAM = n-methyl-d-aspartate Receptor Subtype 2B Negative Allosteric Modulator; VMAT2 = Vesicular Monoamine Transporter 2; M1 = M1 Muscarinic Receptor Neurocrine Biosciences Partners: * Partnered with Takeda Pharmaceutical Company Limited; ** In-Licensed from Nxera Pharma UK Limited (formerly Sosei Heptares) Conference Call and Webcast Today at 8:00 AM Eastern Time Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-445-7795 (US) or 785-424-1699 (International) using the conference ID: NBIX. The webcast and accompanying slides can also be accessed at approximately 8:00 a.m. Eastern Time on Neurocrine Biosciences' website under Investors at . A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month. About Neurocrine Biosciences Neurocrine Biosciences is a neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. 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, 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) NEUROCRINE BIOSCIENCES, NEUROCRINE and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. The Neurocrine logo is a trademark of Neurocrine Biosciences, Inc. Non-GAAP Financial Measures In addition to the financial results and financial guidance that are provided in accordance with accounting principles generally accepted in the United States (GAAP), this press release also contains the following Non-GAAP financial measures: Non-GAAP R&D expense, Non-GAAP SG&A expense, and Non-GAAP net income and net income per share. When preparing the Non-GAAP financial results and guidance, the Company excludes certain GAAP items that management does not consider to be normal, including recurring cash operating expenses that might not meet the definition of unusual or non-recurring items. In particular, these Non-GAAP financial measures exclude: non-cash stock-based compensation expense, charges associated with convertible senior notes, impairment charges associated with leased properties, non-cash amortization expense related to acquired intangible assets, acquisition and integration costs, changes in fair value of equity security investments, changes in foreign currency exchange rates and certain adjustments to income tax expense. These Non-GAAP financial measures are provided as a complement to results provided in accordance with GAAP as management believes these Non-GAAP financial measures help indicate underlying trends in the Company's business, are important in comparing current results with prior period results and provide additional information regarding the Company's financial position. Management also uses these Non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally and to manage the Company's business and evaluate its performance. The Company provides guidance regarding combined R&D and SG&A expenses on both a GAAP and a Non-GAAP basis. A reconciliation of these GAAP financial results to Non-GAAP financial results is included in the attached financial information. 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 related to: the benefits to be derived from our products and product candidates; the value our products and/or our product candidates may bring to patients; the continued success of INGREZZA; our financial and operating performance, including our future revenues, expenses, or profits; our collaborative partnerships; expected future clinical and regulatory milestones; and the timing of the initiation and/or completion of our clinical, regulatory, and other development activities and those of our collaboration partners. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: our future financial and operating performance; risks and uncertainties associated with the commercialization of INGREZZA; risks that the crinecerfont New Drug Applications (NDAs) may not obtain regulatory approval, such approval may be delayed, or may not receive the benefits associated with priority review; risks related to the development of our product candidates; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates 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 associated with government and third-party regulatory and/or policy efforts which may, among other things, impose sales and pharmaceutical pricing controls on our products or limit coverage and/or reimbursement for our products; risks associated with competition from other therapies or products, including potential generic entrants for our products; and other risks described in our periodic reports filed with the SEC, including our Quarterly Report on Form 10-Q for the quarter ended June 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than as required by law. SOURCE Neurocrine Biosciences, Inc.

Phase 1Financial StatementPhase 2Clinical ResultPhase 3

02 Jul 2024

·www.pharmaceutical-technology.com

FDA grants priority review for Neurocrine’s crinecerfont NDAs

The asset is intended to treat congenital adrenal hyperplasia in paediatric and adult patients. Credit: YURIMA / Shutterstock. The US Food and Drug Administration (FDA) has accepted Neurocrine Biosciences ’ new drug applications (NDAs) for crinecerfont to treat classic congenital adrenal hyperplasia (CAH), and has granted priority review. Crinecerfont is the first new CAH treatment option in paediatric and adult patients in seven decades. The NDAs for crinecerfont include a capsule formulation (NDA# 218808) and an oral solution formulation (NDA# 218820). The applications are supported by data from the CAHtalyst Pediatric and CAHtalyst Adult Phase III clinical trials. A regulatory decision on the approvals for the asset is expected by 29 and 30 December 2024 respectively. See Also: Eisai and Bristol Myers Squibb terminate ADC development deal Orion to hand over exclusive rights to MSD for prostate cancer therapy The priority review status aids in reducing the regulator’s review period by four months. Approval of crinecerfont would also allow Neurocrine to utilise its rare paediatric disease designation priority review voucher, which was awarded in September 2020. In March 2019 and December 2023, crinecerfont received orphan drug and breakthrough therapy designations. The FDA granted the breakthrough therapy status based on the results and safety profile of the asset in the Phase III CAHtalyst studies. Neurocrine Biosciences chief medical officer Eiry Roberts said: “Receipt of a priority review reflects the FDA’s agreement that CAH is a serious condition and there is an urgent need for patients to have access to new treatments. “Crinecerfont’s compelling efficacy results and excellent safety profile support our filing, and we look forward to working with the FDA as we head toward the PDUFA dates at the end of 2024.” In May 2024 the FDA approved an alternative formulation for Neurocrine Biosciences’ Huntington’s disease therapy, Ingrezza (valbenazine).

Priority ReviewPhase 3NDABreakthrough TherapyOrphan Drug

100 Deals associated with Crinecerfont

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Classic Congenital Adrenal Hyperplasia	US	Neurocrine Biosciences, Inc.	13 Dec 2024

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	US	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	BE	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	CA	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	FR	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	DE	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	GR	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	IT	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	PL	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	ES	Neurocrine Biosciences, Inc.	25 Jun 2021
Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency	Phase 3	GB	Neurocrine Biosciences, Inc.	25 Jun 2021

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04045145 (CTgov)	Phase 2	Adrenal Hyperplasia, Congenital	8	Crinecerfont	ojbuvcwxbi(bgtgdqcted) = ehsswydnsi udibrgrebq (njhzppytmo, bbyfdrdgkx - kphwlquoep) View more	-	18 Jul 2024
NCT04490915 (CAHtalyst, Pubmed)	Phase 3	Adrenal Hyperplasia, Congenital 21-hydroxylase deficiency	182	Crinecerfont	muuhxmxlsq(phadycgrry) = Fatigue were the most common adverse events in the two trial groups wdkhghwycs (bxfyxoixyx ) View more	Positive	01 Jun 2024
NCT04490915 (CAHtalyst, Pubmed)	Phase 3	Adrenal Hyperplasia, Congenital 21-hydroxylase deficiency	182	Placebo		Positive	01 Jun 2024
CAHtalyst (PRNewswire) Manual	Phase 3	Adrenal Hyperplasia, Congenital	-	crinecerfont	lohckmunso(iguuhzekwz) = a statistically significant decrease in serum androstenedione from baseline with crinecerfont at Week 4 over baseline, while both studies showed crinecerfont treatment led to statistically significant reductions in daily glucocorticoid from baseline while maintaining androgen control at Week 28 and Week 24, respectively mxqllwkqpr (htlmheruci ) View more	Positive	05 Dec 2023
NCT03525886 (CTgov)	Phase 2	Adrenal Hyperplasia, Congenital	18	NBI-74788 (Cohort 1 (50 mg QHS))	kgxbvsbdzs(nobvipuodl) = uuelyzlbmk nzpxkjkqex (gtjgjawlci, cpldmffvfl - fjltddusja) View more	-	03 May 2022
NCT03525886 (CTgov)	Phase 2	Adrenal Hyperplasia, Congenital	18	NBI-74788 (Cohort 2 (100 mg QHS))	kgxbvsbdzs(nobvipuodl) = soefobzyyb nzpxkjkqex (gtjgjawlci, cusekwiqwn - duiydujvkl) View more	-	03 May 2022
NCT03525886 (Pubmed \| J Clin Endocrinol Metab) Manual	Phase 2	Adrenal Hyperplasia 2	18	Crinecerfont	xwcrcilhlc(teglsldkpl) = nczetpnodf gmmchjpama (blkmfyvlxi ) View more	Positive	17 Feb 2022
NCT03525886 (PRNewswire) Manual	Phase 2	Adrenal Hyperplasia, Congenital	30	Crinecerfont	mvglwisutc(giydlpivfe) = cegebqoarn gjkkhlabmy (drjwnkprde ) View more	Positive	12 Mar 2019
SFN2003	Not Applicable	Aggression	-	SSR125543A 30 mg/kg	ntwmeoromj(lonfetdbii) = wyflwwgfkx jrrhwscwjj (mbgcnzzdnt ) View more	-	09 Nov 2003

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis