Spruce Biosciences Announces Topline Results from CAHmelia-204 in Adult CAH and CAHptain-205 in Adult and Pediatric CAH
Spruce Biosciences (NASDAQ: SPRB) announced disappointing topline results from two clinical trials evaluating tildacerfont for Congenital Adrenal Hyperplasia (CAH). The CAHmelia-204 Phase 2b study failed to meet its primary endpoint of reducing glucocorticoid usage in adult CAH patients. The trial showed a minimal placebo-adjusted reduction of 0.7mg in daily glucocorticoid dose.
The CAHptain-205 Phase 2 study suggested that higher doses and twice-daily (BID) dosing may be necessary for efficacy. While tildacerfont was generally safe and well-tolerated in both trials, the company will discontinue these clinical trials and wind down its investment in tildacerfont for CAH treatment while evaluating strategic options and implementing cost-reduction measures.
Spruce Biosciences (NASDAQ: SPRB) ha annunciato risultati deludenti dai due studi clinici che valutano il tildacerfont per l'ipoadrenalismo congenito (CAH). Lo studio CAHmelia-204 di Fase 2b non ha raggiunto l'obiettivo primario di ridurre l'uso di glucocorticoidi nei pazienti adulti con CAH. Lo studio ha mostrato una riduzione minima, corretta per il placebo, di 0,7 mg nella dose giornaliera di glucocorticoidi.
Lo studio CAHptain-205 di Fase 2 ha suggerito che dosi più elevate e somministrazione due volte al giorno (BID) potrebbero essere necessarie per l'efficacia. Sebbene il tildacerfont si sia dimostrato generalmente sicuro e ben tollerato in entrambi gli studi, l'azienda interromperà questi studi clinici e ridurrà il suo investimento nel tildacerfont per il trattamento della CAH, valutando opzioni strategiche e implementando misure di riduzione dei costi.
Spruce Biosciences (NASDAQ: SPRB) anunció resultados decepcionantes de dos ensayos clínicos que evalúan el tildacerfont para la hiperplasia suprarrenal congénita (CAH). El estudio CAHmelia-204 de Fase 2b no logró cumplir con su objetivo principal de reducir el uso de glucocorticoides en pacientes adultos con CAH. El ensayo mostró una reducción mínima ajustada por placebo de 0.7 mg en la dosis diaria de glucocorticoides.
El estudio CAHptain-205 de Fase 2 sugirió que podrían ser necesarias dosis más altas y una dosificación dos veces al día (BID) para lograr eficacia. Aunque el tildacerfont fue generalmente seguro y bien tolerado en ambos ensayos, la empresa decidirá discontinuar estos ensayos clínicos y disminuir su inversión en tildacerfont para el tratamiento de la CAH mientras evalúa opciones estratégicas e implementa medidas de reducción de costos.
Spruce Biosciences (NASDAQ: SPRB)는 선천적 부신 과형성증(CAH) 치료를 위한 tildacerfont에 대한 두 개의 임상 시험에서 실망스러운 주요 결과를 발표했습니다. CAHmelia-204 2b상 연구는 성인 CAH 환자에서 글루코코르티코이드 사용을 줄이는 주요 목표를 달성하지 못했습니다. 이 시험은 일일 글루코코르티코이드 용량에서 0.7mg의 최소한의 위약 조정 감소를 보여주었습니다.
CAHptain-205 2상 연구는 효능을 위해 더 높은 용량과 하루 두 번(BID)의 투여가 필요할 수 있음을 시사했습니다. tildacerfont는 두 응시 모두에서 일반적으로 안전하고 잘 견뎌내는 반면, 회사는 이러한 임상 시험을 중단하고 CAH 치료를 위한 tildacerfont에 대한 투자를 축소하며 전략적 옵션을 평가하고 비용 절감 조치를 시행할 것입니다.
Spruce Biosciences (NASDAQ: SPRB) a annoncé des résultats décevants de deux essais cliniques évaluant le tildacerfont pour l'hyperplasie surrénale congénitale (CAH). L'étude CAHmelia-204 Phase 2b n'a pas atteint son objectif principal de réduction de l'utilisation des glucocorticoïdes chez les patients adultes atteints de CAH. L'essai a montré une réduction minimale corrigée par placebo de 0,7 mg dans la dose quotidienne de glucocorticoïdes.
L'étude CAHptain-205 Phase 2 a suggéré que des doses plus élevées et une posologie deux fois par jour (BID) pourraient être nécessaires pour l'efficacité. Bien que le tildacerfont ait été généralement sûr et bien toléré dans les deux essais, l'entreprise va interrompre ces essais cliniques et réduire son investissement dans le tildacerfont pour le traitement de la CAH tout en évaluant des options stratégiques et en mettant en œuvre des mesures de réduction des coûts.
Spruce Biosciences (NASDAQ: SPRB) gab enttäuschende Ergebnisse aus zwei klinischen Studien bekannt, die tildacerfont zur Behandlung der kongenitalen adrenalen Hyperplasie (CAH) untersuchten. Die CAHmelia-204 Phase 2b-Studie erreichte nicht das primäre Ziel, den Glukokortikoidverbrauch bei Erwachsenen mit CAH zu reduzieren. Die Studie zeigte eine minimale placebo-korrigierte Reduktion von 0,7 mg in der täglichen Glukokortikoiddosis.
Die CAHptain-205 Phase 2-Studie deutete darauf hin, dass höhere Dosen und eine zweimal tägliche (BID) Dosierung für die Wirksamkeit notwendig sein könnten. Obwohl tildacerfont in beiden Studien im Allgemeinen sicher und gut verträglich war, wird das Unternehmen diese klinischen Studien einstellen und seine Investitionen in tildacerfont zur Behandlung von CAH zurückfahren, während es strategische Optionen evaluiert und Kostensenkungsmaßnahmen umsetzt.
- Tildacerfont demonstrated good safety profile with no serious adverse events
- High patient compliance rate of 98% in CAHmelia-204 study
- CAHmelia-204 Phase 2b trial failed to meet primary endpoint
- Company discontinuing clinical trials and winding down tildacerfont investment
- Need for higher doses and more frequent dosing indicates current formulation ineffectiveness
- Strategic review and cost-reduction activities signal potential financial concerns
Insights
CAHmelia-204 Study of 200mg Once-Daily (QD) Tildacerfont in Adult Congenital Adrenal Hyperplasia (CAH) Did Not Achieve Primary Endpoint of Glucocorticoid (GC) Reduction
Dose-Ranging Data from CAHptain-205 Study of Tildacerfont in Adult and Pediatric CAH Suggests Higher Doses and Twice-Daily (BID) Dosing May Be Necessary for Efficacy in CAH
Evaluation of Strategic Opportunities and Cost-Reduction Activities Underway
“We are very grateful to all the patients, families, investigators, and the entire CAH community who supported the CAHmelia-204 and CAHptain-205 clinical trials. We garnered invaluable safety and exposure response data on tildacerfont from these studies, which suggests that higher doses and more frequent dosing may be necessary for efficacy in CAH,” said Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer of Spruce. “Moving forward, we plan to evaluate a full range of strategic options for Spruce in addressing diseases with serious unmet need for patients. In the interim, the CAHmelia-204 and CAHptain-205 clinical trials will be discontinued, and we will be winding down Spruce’s investment in tildacerfont for the treatment of CAH as we conserve financial resources and look to maximize shareholder value.”
CAHmelia-204 was a Phase 2b, randomized, double-blind, placebo-controlled clinical trial that evaluated the safety and efficacy of tildacerfont in reducing supraphysiologic GC usage in 100 adults with classic CAH on a mean GC dose of 35mg/day of hydrocortisone equivalents (HCe) (19mg/m2/day) and mean androstenedione (A4) level of 214 ng/dL at baseline.
The clinical trial did not achieve the primary efficacy endpoint of the absolute change in daily GC dose from baseline at week 24. 200mg QD of tildacerfont demonstrated a placebo-adjusted reduction from baseline in daily GC dose of 0.7mg HCe (
“Although the study missed its primary endpoint, the data offers valuable insights that will shape the future of CAH management and research,” said Jung Hee Kim, M.D., M.S., Ph.D., Principal Investigator and Associate Professor of Internal Medicine, Seoul National University Hospital and College of Medicine. “I am grateful to the nearly 400 CAH patients who shared their information with us and look forward to presenting our findings at upcoming conferences in 2025.”
CAHptain-205 was a Phase 2 open-label, 4-week, sequential cohort clinical trial, that evaluated the safety, pharmacodynamics (changes in A4 levels), and pharmacokinetics of QD and BID doses of tildacerfont from 50mg QD to 400mg BID in pediatric and adult patients with CAH. A trend was observed of larger reductions from baseline in A4 levels with higher BID doses of tildacerfont. Tildacerfont was generally safe and well tolerated across all doses with no drug-related SAEs.
“This study was well-run with excellent compliance,” said Paul Thornton, M.B.B.S., Principal Investigator and Medical Director of the Endocrine and Diabetes Program at a CAH Center of Excellence. “The data suggests that a twice-daily dosing may be more effective.”
About CAHmelia-204
CAHmelia-204 was a Phase 2b, randomized, double-blind, placebo-controlled clinical trial that evaluated the safety and efficacy of tildacerfont in reducing supraphysiologic glucocorticoid (GC) usage in 100 adults with classic congenital adrenal hyperplasia (CAH) on supraphysiologic doses of GCs with normal or near normal levels of androstenedione (A4) at baseline. In the first part of the clinical trial, patients were randomized to receive 200mg of tildacerfont once-daily (QD) or placebo for 24 weeks. During the second part of the clinical trial, all patients received 200mg of tildacerfont QD for 52 weeks. Throughout the trial, tapering of GCs was guided according to a pre-specified algorithm based on A4 normalization. The primary endpoint of the clinical trial was the absolute change in daily GC dose in hydrocortisone equivalents (HCe) from baseline through week 24.
About CAHptain-205
CAHptain-205 was a Phase 2 open-label clinical trial, which utilized a sequential nine cohort design, to evaluate the safety, efficacy, and pharmacokinetics of tildacerfont in adults and children between two and 17 years of age with CAH. Cohorts 1-3 evaluated weight-adjusted doses of tildacerfont between 50mg QD and 200mg QD in pediatric CAH patients between two and 17 years of age and assessed changes in androgen levels over 12 weeks of treatment as well as the ability to reduce daily GC dose based on A4 normalization. Cohorts 4-9 evaluated weight-adjusted doses of tildacerfont of 200mg twice-daily (BID) and 400mg BID in adults and children between two and 17 years of age with CAH to assess changes in androgen levels over four weeks of treatment.
About Congenital Adrenal Hyperplasia (CAH)
CAH is an autosomal recessive disease, driven by a mutation in the gene that encodes an enzyme necessary for the synthesis of key adrenal hormones. In CAH patients, the body is not able to produce cortisol, leading to serious health consequences. The absence of cortisol alters the normal feedback cycle of the hypothalamic-pituitary-adrenal (HPA) axis and leads to excess secretion of adrenocorticotropic hormone (ACTH), hyperplasia of the adrenal gland, and consequently high levels of adrenal androgen production. As a result, CAH patients may suffer from premature puberty, impaired fertility, hirsutism, acne, the development of adrenal rest tumors, and an impaired quality of life, and additionally for females, virilized genitalia and menstrual irregularities. Currently, the only way to downregulate the production of excess androgens in CAH patients is to administer supraphysiologic doses of GCs, which present specific side effects, including increased risks of developing diabetes, cardiovascular disease, stunted growth, osteoporosis, thin skin, gastrointestinal disorders, and decreased lifespan.
About Tildacerfont
Tildacerfont is a potent and highly selective, non-steroidal, once-daily oral antagonist of the CRF1 receptor, which is the receptor for corticotropin-releasing factor (CRF), a hormone that is secreted by the hypothalamus. The CRF1 receptor is abundantly expressed in the pituitary gland where it is the primary regulator of the HPA axis. By blocking the CRF1 receptor, tildacerfont has the potential to address the uncontrolled cortisol feedback regulatory pathway in CAH, and in turn reduce the production of ACTH in the pituitary, limiting the amount of androgen produced downstream from the adrenal gland. By controlling excess adrenal androgens through an independent mechanism, tildacerfont has the potential to reduce the unwanted clinical symptoms associated with high androgen exposure and could also enable treating physicians to lower the supraphysiologic GC doses given to CAH patients to near physiologic levels. No drug-related serious adverse events have been reported related to tildacerfont treatment in completed studies.
About Spruce Biosciences
Spruce Biosciences is a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological and endocrine disorders with significant unmet medical need. To learn more, visit www.sprucebio.com and follow us on X, LinkedIn, Facebook and YouTube.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the Company’s plans to evaluate a full range of strategic options, the discontinuance of the CAHmelia-204 and CAHptain-205 clinical trials, and the wind-down of the Company’s investment in tildacerfont for the treatment of CAH. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “anticipate”, “will”, “potential”, “plan” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Spruce’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Spruce’s business in general, the impact of geopolitical and macroeconomic events, and the other risks described in Spruce’s filings with the
View source version on businesswire.com: https://www.businesswire.com/news/home/20241210266378/en/
Media
Katie Beach Oltsik
Inizio Evoke Comms
(937) 232-4889
Katherine.Beach@inizioevoke.com
media@sprucebio.com
Investors
Samir Gharib
President and CFO
Spruce Biosciences, Inc.
investors@sprucebio.com
Source: Spruce Biosciences, Inc.
FAQ
What were the results of Spruce Biosciences' CAHmelia-204 trial for SPRB stock?
What is happening to tildacerfont development at Spruce Biosciences (SPRB)?
What were the safety results for tildacerfont in SPRB's clinical trials?
