MedPath

Zuranolone

Generic Name
Zuranolone
Drug Type
Small Molecule
Chemical Formula
C25H35N3O2
CAS Number
1632051-40-1
Unique Ingredient Identifier
7ZW49N180B
Background

Zuranolone is a neuroactive steroid that acts as a positive allosteric modulator of the GABA receptors. Unlike other more common GABA positive allosteric modulators on the market like benzodiazepines, zuranolone can modulate both synaptic and extrasynaptic GABA conductance due to binding to a non-benzodiazepine site on the receptor. Zuranolone was designed with a pharmacological profile of a neuroactive steroid in mind while also possessing a pharmacokinetics profile of an oral, once-daily dosing formulation.

Zuranolone was approved by the FDA on August 4th, 2023, and it is currently the only approved treatment for women with postpartum depression. This approval was based on favorable results from 2 phase 3 clinical trials.

Indication

Zuranolone is indicated for the treatment of postpartum depression (PPD) in adults.

Associated Conditions
Postpartum Depression

Tenax Therapeutics Appoints Gillian Andor as VP of Clinical Operations to Bolster Phase 3 Program

• Tenax Therapeutics has appointed Gillian Andor as Vice President of Clinical Operations to support its Phase 3 program for oral levosimendan (TNX-103). • Ms. Andor brings over 20 years of experience in clinical operations, including NDA submissions and approvals, to accelerate the Phase 3 LEVEL study. • Her expertise will be crucial as Tenax Therapeutics advances oral levosimendan for pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). • The appointment signifies Tenax's commitment to strengthening its clinical development capabilities as it prepares for potential global regulatory filings.

FDA Approves J&J's Spravato as First Monotherapy for Treatment-Resistant Depression

• The FDA has approved Spravato (esketamine) nasal spray as a standalone treatment for adults with major depressive disorder who have not responded to other antidepressants. • Spravato demonstrated rapid and superior improvement in depressive symptoms compared to placebo, with benefits observed as early as 24 hours after administration. • The approval is based on a Phase IV study showing that 22.5% of Spravato-treated patients achieved remission at four weeks, compared to 7.6% in the placebo group. • Spravato's label includes warnings about sedation, dissociation, and potential for misuse, and it is only available through a restricted program with medical supervision.

FDA Extends Review Period for Biogen's SOD1-ALS Therapy Tofersen

The FDA has extended its review timeline for Biogen's tofersen, an experimental therapy for SOD1-mutated ALS, by three months, pushing the decision date from January to April. The delay follows Biogen's submission of additional information deemed a "major amendment" by the FDA, while the company continues to provide the drug through its early-access program.

Sage and Biogen's Zuranolone Shows Promise in Phase 3 Trials but Faces Commercial Uncertainty

Sage Therapeutics and Biogen's antidepressant zuranolone has shown efficacy in phase 3 trials, with a significant reduction in depression symptoms at three days. However, concerns about the durability of its effects and commercial viability remain, despite plans to file for marketing approval.

FDA Panel Approves Sage's Novel Antidepressant for Postnatal Depression, Rejects Alkermes' Treatment

An FDA advisory committee has voted in favor of Sage's Zulresso (brexanolone) for the treatment of postnatal depression, marking a significant step towards its approval as the first specific drug for this condition. However, the same panel rejected Alkermes' ALKS 5461 for major depressive disorder, citing concerns over its benefit-risk profile and trial design.

Key Advances in Neuromuscular and Movement Disorder Treatments Highlighted in 2024

• AbbVie's Vyalev, a 24-hour subcutaneous levodopa infusion, gained FDA approval for managing motor fluctuations in advanced Parkinson's, offering a novel therapeutic approach. • Intellia's CRISPR therapy, NTLA-2001, demonstrated safe redosing in ATTR amyloidosis patients, achieving additive pharmacodynamic effects on the target protein. • A phase 3 study revealed that buntanetap is a safe and well-tolerated drug which improves motor, nonmotor, and cognitive symptoms of Parkinson's disease. • The FDA supported using αSyn-SAA biomarker in Parkinson's clinical trials, enhancing therapeutic development through improved diagnostic precision.

Sage Therapeutics' Dalzanemdor Fails in Huntington's Disease Trial, Pipeline Thins

• Sage Therapeutics' dalzanemdor failed in the Phase II DIMENSION trial for Huntington's disease, leading to the discontinuation of its development. • This setback follows previous failures of dalzanemdor in Parkinson's and Alzheimer's, further impacting Sage's clinical pipeline. • Sage is now heavily reliant on Zurzuvae for postpartum depression, with strategic reorganizations aimed at supporting its commercial launch. • Analysts express concerns about Sage's path to profitability despite cost-cutting measures and the initial success of Zurzuvae.

Cybin's CYB003 Shows Sustained Remission in Major Depressive Disorder After 12 Months

• Cybin's CYB003, a deuterated psilocin drug, demonstrates a 71% sustained remission rate in patients with major depressive disorder (MDD) after 12 months. • The Phase 2 trial results showed a 100% response rate at 12 months following two administrations of 16 mg doses of CYB003 spaced three weeks apart. • CYB003 has received Breakthrough Therapy Designation from the FDA, potentially expediting its review process for treating MDD due to its significant improvement over existing therapies. • Cybin has initiated the Phase 3 PARADIGM program to further evaluate the efficacy and safety of CYB003 in a broader MDD patient population globally.

Cybin's CYB003 Shows Sustained Efficacy in Phase 2 Depression Study

• Cybin's CYB003 demonstrated a 100% response rate and 71% remission rate in MDD patients after two 16mg doses, three weeks apart. • The Phase 2 study showed sustained treatment benefits through 12 months, validating the dosing regimen and durable effects of CYB003. • CYB003 has received Breakthrough Therapy Designation from the FDA, potentially expediting its review pathway for MDD treatment. • Cybin is advancing CYB003 into Phase 3 trials, expected to begin by the end of 2024, to further evaluate its efficacy in a larger MDD population.

Biogen's Growth Prospects Face Challenges Amidst Leqembi's Slow Uptake

• Needham downgraded Biogen, projecting flat revenue until 2026 due to slow sales growth of Alzheimer's drug Leqembi and the time needed for new products to offset declines. • Leqembi's global sales reached $67 million in Q3, with $39 million from the U.S., but physician feedback suggests a continued gradual increase in sales, tempering market expectations. • Skyclarys' Q4 sales are projected to reach $116 million, with $608 million expected for 2025, while Zurzuvae's Q3 sales were reported at $22 million, contributing to Biogen's revenue diversification. • Despite a positive recommendation for Leqembi in the EU, Needham anticipates Biogen's revenues to remain flat or slightly decline until 2026, leading to a downgrade of the stock.

Biogen's Revenue Growth Stalled: Analyst Downgrade Cites Slow Leqembi Uptake

• Needham downgraded Biogen, projecting flat revenue until 2026 due to limited growth catalysts and slow sales of Alzheimer's drug Leqembi. • Leqembi's Q3 global sales reached $67 million, with $39 million in the U.S., but physician feedback suggests a continued gradual uptake. • Skyclarys is projected to reach $116 million in Q4 sales and $608 million in 2025, while Zurzuvae's Q3 sales were $22 million. • Despite EMA's positive opinion on lecanemab, Biogen faces challenges in meeting market expectations and offsetting declines in existing business.

AbbVie's Emraclidine Fails in Phase II Schizophrenia Trials, Shares Plummet

• AbbVie's emraclidine failed to demonstrate statistically significant improvement in schizophrenia symptoms compared to placebo in two Phase II trials. • The failure led to a 12% drop in AbbVie's shares, raising concerns about the company's long-term growth strategy and neuroscience pipeline. • Analysts highlight the surprisingly high placebo response in the trials, while others point to potential implications for the broader CNS drug development landscape. • Bristol Myers Squibb's recently approved Cobenfy (KarXT) for schizophrenia may benefit from AbbVie's setback, potentially reaching peak sales of $4 billion.

Sage Therapeutics Restructures, Cuts Workforce Amid Pipeline Setbacks

• Sage Therapeutics is laying off one-third of its workforce and streamlining its early-stage drug pipeline after clinical and regulatory setbacks. • The restructuring follows the FDA's limited approval of Zurzuvae for postpartum depression and clinical failures of dalzanemdor in Alzheimer's and Parkinson's diseases. • Sage will prioritize the commercial launch of Zurzuvae and focus its pipeline development efforts on dalzanemdor for Huntington's disease. • The company anticipates incurring $26-28 million in restructuring costs in Q4 2024 to strengthen its financial position.

Zuranolone Offers Rapid Relief for Rural Iowa Mothers with Postpartum Depression

• Zuranolone, the first oral medication for postpartum depression (PPD), is being prescribed in Iowa, offering a new treatment option. • Rural Iowa mothers face increased odds of PPD due to limited access to mental healthcare and stigma, making zuranolone a crucial advancement. • Clinical trials showed zuranolone can be effective within days, a significant improvement over previous treatments like lengthy intravenous infusions. • Risk factors for PPD include a history of anxiety or mood disorders, family history of depression, and being from underserved communities.

Sage Therapeutics Navigates Pipeline Hurdles Amidst Zurzuvae Launch

• Sage Therapeutics is focused on the launch of Zurzuvae for postpartum depression, with early metrics tracking in line with expectations. • Dalzanemdor (SAGE-718) is a key pipeline drug in Phase II trials for Huntington's and Alzheimer's diseases, bearing high risk and potential reward. • Financial projections indicate revenue growth, but profitability remains uncertain, emphasizing the need for expense management. • Analysts highlight the competitive CNS market and the importance of Zurzuvae's market penetration and pipeline advancements for Sage's future.

Shionogi Submits Zuranolone NDA in Japan for Major Depressive Disorder

• Shionogi has submitted a New Drug Application (NDA) in Japan for zuranolone, targeting the treatment of major depressive disorder (MDD). • The NDA is supported by Phase 3 trial data in Japan, which demonstrated statistically significant improvements in MDD symptoms. • Zuranolone, a neuroactive steroid GABA-A receptor modulator, has shown rapid efficacy, potentially addressing the need for faster-acting treatments. • Zuranolone is already approved in the U.S. for postpartum depression and could offer a novel treatment option for MDD in Japan.

FDA Approves Zuranolone: First Oral Treatment for Postpartum Depression

• The FDA has approved zuranolone, marketed as a once-daily oral medication, marking the first treatment specifically for postpartum depression (PPD). • Clinical trials demonstrated significant improvements in depressive symptoms for women taking zuranolone compared to placebo, offering a new therapeutic option. • Zuranolone represents a novel approach to PPD treatment, potentially improving access and reducing the burden of this common complication after pregnancy. • The approval of zuranolone provides a much-needed alternative to existing treatments, addressing a significant unmet need in women's healthcare.
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