-=Sage Therapeutics (SAGE) : positive data from ongoing Phase 3 open-label SHORELINE Study

 

SAGE Therapeutics announces positive interim, topline zuranolone safety and tolerability data from open-label shoreline study in patients with MD

Co reported interim, topline results from a July data cut of the ongoing Phase 3 open-label SHORELINE Study. This clinical study was designed to naturalistically follow patients with major depressive disorder (MDD) and evaluate the safety and tolerability of zuranolone 30 mg in adults for up to one year. In May 2020, the protocol was amended to include a 50 mg dose of zuranolone. For the primary endpoint of safety and tolerability, the data analyzed to date show that zuranolone was generally well-tolerated in the 30 mg dose and among the initial patients treated with the 50 mg dose. Adverse events reported in the trial during the period analyzed were generally consistent with results seen in previous clinical trials.

Secondary endpoints included response and remission as evaluated by the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the number of times a patient received retreatment. At the time of this analysis, patients with a clinical response (decrease in HAMD-17 baseline score of =50%) to the initial 14-day course of zuranolone 30 mg used a mean number of 1.9 treatments per year.

-=Sage Therapeutics (SAGE) : Depression drug unexpectedly fails

• Reports top-line results from pivotal Phase 3 MOUNTAIN Study evaluating the effect of SAGE-217 on depressive symptoms in adults with major depressive disorder; study did not meet primary endpoint at Day 15.

Sage Therapeutics (SAGE) collapsed Thursday after the biotech company's depression treatment failed to pass muster in a Phase 3 study. In early action on today's stock market, Sage stock plunged near 60%, and stood at roughly 60 a share.

This is the first time Sage's depression treatment, SAGE-217, missed its key goal in a test for major depressive disorder, SVB Leerink analyst Marc Goodman said in a note to clients. He has an underperform rating on Sage stock.

"The stock in premarket trading is down in the $60 range that we had previously outlined ($55-$90) as the worst case scenario," he said.

Depression Treatment Misses Its Mark

Patients took a daily pill of SAGE-217 as a depression treatment. The drug showed a statistically significant improvement on the symptoms of depression compared to a placebo on days three, eight and 12. Researchers used a scale called the Hamilton Rating Scale for Depression.

But on day 15, the depression treatment showed an average reduction of 12.6 points on that scale, compared to an average reduction of 11.2 points for the placebo. The results were not statistically significant.

In an analysis following the study, the biotech company noted two key issues. It appeared 9% of patients weren't compliant in taking a daily dose of the depression treatment. In addition, the study enrolled patients with milder symptoms than previous studies.

Sage suggested if these patients were excluded, the study would have hit its mark.

Treatment Well Tolerated

Sage noted the depression treatment was generally well tolerated. Overall adverse events in the 14-day treatment window and during 28 days of follow-up were similar between SAGE-217 and the placebo.

Chief Executive Jess Jonas reiterated his hopes for the depression treatment, noting SAGE-217 displays "good activity on most measures."

"We understand the drug development is an iterative process," he said in a written statement. "In the study, we've gathered new data on SAGE-217, data we believe support our hypothesis that SAGE-217 has a unique profile with the potential for rapid and robust onset with durable effect."

-=SAGE Therapeutics (SAGE) : expedited development plan for SAGE-217 following a Breakthrough Therapy meeting with the FDA

SAGE Therapeutics announces expedited development plan for SAGE-217 following a Breakthrough Therapy meeting with the FDA 

This development plan is intended to support a potential filing for approval of SAGE-217 in the U.S. for the treatment of major depressive disorder (MDD) and postpartum depression (PPD).

• The expedited development plan for SAGE-217 includes a single additional placebo-controlled Phase 3 pivotal trial in patients with MDD and the ongoing placebo-controlled trial in women with PPD, now designated a pivotal trial. Both clinical trials are designed to evaluate the novel concept of episodic dosing, or short course treatment, with SAGE-217 and its effect on the reduction of depressive symptoms compared to placebo. An open-label study will evaluate the potential of episodic treatment for recurrent or new major depressive episodes and provide additional safety data.
• Sage plans to initiate the placebo-controlled Phase 3 trial in MDD during the second half of 2018. Further, Sage anticipates announcing top-line data from the placebo-controlled pivotal trial of SAGE-217 in PPD in the fourth quarter of 2018. This expedited pivotal program is supported by the results of a positive placebo-controlled trial in patients with MDD announced in December 2017.

=Incyte (INCY) and Merck (MRK) : failed key Phase 3 melanoma study

• Biotech stocks (XBI) lower after important immune-oncology combo data (Incyte's IDO inhibitor plus Merck's Keytruda) fails in key Phase 3 melanoma study:  NLNK (IDO inhibitor peer) -37.57%,  INCY -18.23%,  NKTR -9.84%,  JNCE -10.20%,  LABU -5.14%,  FPRX -3.84%,  ONCS -3.72%,  SAGE -2.21%,  SGEN -1.81%,  BLUE -4.85%,  PBYI-1.85%,  SPPI -2.46%,  CRVS -9.17%,  TSRO +0.37%,  BMRN -2.01%, GLYC-2.03%, MRK-1.19% 
• IBB -1.99%,  XBI -1.78%

Incyte announces that the External Data Monitoring Committee determined that the Phase 3 ECHO-301/KEYNOTE-252 study did not meet the primary endpoint 

The co and Merck (MRK) announced that an external Data Monitoring Committee review of the pivotal Phase 3 ECHO-301/KEYNOTE-252 study results evaluating Incyte's epacadostat in combination with Merck's KEYTRUDA in patients with unresectable or metastatic melanoma determined that the study did not meet the primary endpoint of improving progression-free survival in the overall population compared to KEYTRUDA monotherapy.

• The study's second primary endpoint of overall survival also is not expected to reach statistical significance. Based on these results, and at the recommendation of the eDMC, the study will be stopped. The safety profile observed in ECHO-301/KEYNOTE-252 was consistent with that observed in previously reported studies of epacadostat in combination with KEYTRUDA.

Incyte and Merck will inform investigators of the results and work with investigators to appropriately conclude the study in a manner consistent with the best interests of each patient. Data from this study will be analyzed and submitted for presentation at an upcoming scientific congress.

Sage Therapeutics (SAGE) reported earnings on Thur 3 Aug 2017 (a/h)

** charts after earnings **

  

 

Sage Therapeutics, Inc. (SAGE), a clinical-stage biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, today reported business highlights and financial results for the second quarter ended June 30, 2017.

“Throughout our six-year history, we have explored innovative methods of drug discovery and development, as well as clinical trial design, in pursuit of novel treatments for CNS disorders that may address gaps in the efficacy and safety profile of current therapies,” said Jeff Jonas, M.D., chief executive officer of Sage. “Our deliberate, thoughtful, and disciplined approach facilitated the potential for two Phase 3 data readouts and multiple other clinical milestone events in the second half of this year. I’m extremely proud of the progress our team has made in a diverse set of disease areas with the goal of positioning Sage for success as a multi-product CNS leader.”

Recent Updates:

Brexanolone in SRSE - Completion of Enrollment in Phase 3 STATUS Trial

Sage recently completed enrollment in the Phase 3 STATUS Trial, the first ever global, randomized, double-blind, placebo-controlled trial in super-refractory status epilepticus (SRSE). Sage continues to expect to report top-line results from the STATUS Trial in the third quarter of 2017, following completion of all study follow-up periods and data analysis.

Brexanolone in PPD – Positive Scientific Advice from European Medicines Agency

In 2016, the European Medicines Agency (EMA) granted PRIority MEdicines (PRIME) designation to brexanolone for the treatment of postpartum depression (PPD). Sage conducted its PRIME meeting with EMA authorities earlier this year and recently received positive scientific advice. Incorporating the scientific advice from the EMA, Sage believes its proposed Phase 3 program, if successful, will be sufficient to support a European Marketing Authorization Application (MAA) to the EMA for the PPD indication. Scientific Advice is a procedure offered by the EMA to stakeholders for clarification of questions arising during development of medicinal products and focuses on development strategies rather than pre-evaluation of data to support an MAA.

SAGE-217 in MDD – Phase 2 Trial Update

Sage is currently conducting a multi-center, double-blind, placebo-controlled, randomized Phase 2 clinical trial of SAGE-217 in major depressive disorder (MDD). Due to the robust pace of enrollment, Sage now plans to increase expected enrollment to approximately 88 patients with moderate to severe MDD, from approximately 66 patients. Sage anticipates reporting top-line results from the Phase 2 trial in the second half of 2017, rather than in 2018.

SAGE-217 in Parkinson’s Disease – Phase 2 Trial Update

Based on a positive activity signal observed in the Part A open-label portion of the Phase 2 program of SAGE-217 in Parkinson's disease, Sage recently initiated an open-label Part B study to evaluate SAGE-217 as an adjunctive treatment in approximately 10 tremor-predominant Parkinson's disease patients. Top-line results from the Part B study are expected in the second half of 2017.

Expected Near-Term Clinical Milestones

• Top-Line Data Readouts:
  • Phase 3 STATUS Trial of brexanolone in SRSE (Q3 2017)
  • Phase 3 Hummingbird Study (202B) of brexanolone in severe postpartum depression (PPD) (2H 2017)
  • Phase 3 Hummingbird Study (202C) of brexanolone in moderate PPD (2H 2017)
  • Phase 2 trial (Part B) of SAGE-217 in MDD (2H 2017)
  • Phase 2 trial of SAGE-217 in essential tremor (2H 2017)
  • Phase 2 trial of SAGE-217 in PPD (2H 2017)
  • Phase 2 trial (Part B) of SAGE-217 in Parkinson’s disease (2H 2017)
  • Phase 1 single-ascending dose trial of SAGE-718 (2H 2017)

Pipeline Overview

Sage is advancing a portfolio of novel CNS product candidates targeting the GABA and NMDA receptor systems. Dysfunction in these systems is known to be at the core of numerous psychiatric and neurological disorders. Sage is pursuing a data-driven approach to CNS drug development by employing efficient human proof-of-concept studies both to uncover activity signals and to help understand future trial methodology, before investing in larger clinical programs.

• Brexanolone (SAGE-547): Sage is currently developing brexanolone in separate Phase 3 clinical programs as an acute interventional treatment for SRSE and PPD. Brexanolone is Sage’s proprietary intravenous (IV) formulation of allopregnanolone, a naturally occurring neuroactive steroid that acts as a synaptic and extrasynaptic modulator of the GABAAreceptor.
  • SRSE: Sage is evaluating brexanolone in the Phase 3 STATUS Trial, a global, randomized, double-blind, placebo-controlled trial, designed to evaluate brexanolone as a potential adjunctive therapy for SRSE, a life-altering and persistent seizure condition with no treatments currently approved by the U.S. Food and Drug Administration (FDA). The Phase 3 clinical program is being conducted in agreement with the FDA under a Special Protocol Assessment (SPA). Sage has also received positive scientific advice from the European Medicines Agency (EMA) with respect to development of brexanolone for SRSE. Based on this advice, the Company believes the Phase 3 clinical program, if successful, will be sufficient to support submission of a marketing authorization application (MAA) to the EMA seeking approval of brexanolone for SRSE in the EU. Top-line results from the Phase 3 STATUS Trial are expected in Q3 2017.
  • PPD: Sage is currently enrolling its Phase 3 clinical program evaluating brexanolone as a potential treatment for PPD, consisting of separate placebo-controlled trials in severe PPD patients (202B) and in moderate PPD patients (202C), collectively known as the Hummingbird Study. In 2016, the FDA granted Breakthrough Therapy Designation and the EMA granted PRIority MEdicines (PRIME) designation to brexanolone for the treatment of PPD. Earlier this year, Sage conducted its PRIME meeting with EMA authorities and recently received positive scientific advice. Top-line results from the Phase 3 clinical trials of brexanolone in PPD are expected in the second half of 2017.
• SAGE-217: Sage’s most advanced, next-generation product candidate is SAGE-217, a novel, orally-active neuroactive steroid that, like brexanolone, is a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. SAGE-217 is currently in Phase 2 development in both mood and movement disorders, with four Phase 2 clinical programs underway.
  • Mood Disorders:
    • MDD: Sage is currently conducting Part B of a Phase 2 clinical trial of SAGE-217 in MDD. Part B of Phase 2 development is a multi-center, double-blind, placebo-controlled, randomized clinical trial of SAGE-217 in MDD. Earlier this year, Sage reported positive clinical results from the open-label Part A portion of the Phase 2 clinical program evaluating SAGE-217 in patients with moderate to severe MDD. The Part B study is expected to evaluate up to approximately 88 patients with moderate to severe MDD for two weeks of treatment with SAGE-217 compared to placebo, with follow-up out to Day 42. Top-line results from the Part B study are expected in the second half of 2017.
    • PPD: Sage is currently conducting a Phase 2 clinical trial of SAGE-217 in PPD. The Phase 2 multi-center, double-blind, placebo-controlled, randomized trial will evaluate the efficacy, safety, tolerability, and pharmacokinetics of SAGE-217 in the treatment of patients with severe PPD. Top-line results from the SAGE-217 PPD study are expected in the second half of 2017.
  • Movement Disorders:
    • Essential tremor: Sage is currently conducting a Phase 2 clinical trial of SAGE-217 in essential tremor. The efficacy, safety, tolerability, and pharmacokinetics of SAGE-217 are being evaluated in a Phase 2 multi-center, double-blind, placebo-controlled, randomized withdrawal trial in the treatment of patients with essential tremor. Top-line results from the SAGE-217 essential tremor study are expected in the second half of 2017.
    • Parkinson's disease: Sage recently initiated an open-label Part B study to evaluate SAGE-217 as an adjunctive treatment in tremor-predominant Parkinson's disease patients. Top-line results from the Part B study are expected in the second half of 2017.
• Other GABA Programs: Sage is currently evaluating a series of novel GABAA receptor modulators in pre-clinical development, including SAGE-324, a novel, orally-active next-generation positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. SAGE-324 is currently in IND-enabling studies, and is intended to be developed with a focus on orphan epilepsies and indications involving GABA hypofunction.
• NMDA Programs: Sage is also developing novel compounds that target the NMDA receptor. The first product candidate selected for development from this program is SAGE-718, a novel, oral, first-in-class oxysterol-based positive allosteric modulator of the NMDA receptor. SAGE-718 is currently in Phase 1 clinical development and Sage expects top-line results from a Phase 1 single-ascending dose trial of SAGE-718 in healthy volunteers in the second half of 2017. Positive modulation of NMDA receptors may have potential in the treatment of a range of neurological disorders associated with a variety of cognitive, neurological and behavioral symptoms.

Financial Results for the Second Quarter of 2017

• Cash Position: Cash, cash equivalents and marketable securities as of June 30, 2017 were $285.9 million, compared with $397.5 million at December 31, 2016.
• R&D Expenses: Research and development expenses were $55.9 million, including $5.2 million of non-cash stock-based compensation expense, in the second quarter of 2017, compared to $26.1 million, including $2.0 million of non-cash stock-based compensation expense, for the same period of 2016. The increase in R&D expense was primarily due to the ongoing clinical development of brexanolone in SRSE and PPD, the ongoing Phase 2 development of SAGE-217, the Phase 1 development of SAGE-718 and investments in R&D headcount to support the growth in Sage’s pipeline and operations.
• G&A Expenses: General and administrative expenses were $15.0 million, including $4.1 million of non-cash stock-based compensation expense, in the second quarter of 2017, compared to $8.9 million, including $2.4 million of non-cash stock-based compensation expense, for the same period of 2016. The increase in G&A expenses was primarily due to the increase in personnel-related expenses, professional fees to support expanding operations, costs related to continued preparations for a potential commercial launch, and facilities-related costs to support expanding operations.
• Net Loss: Net loss was $70.2 million for the second quarter of 2017, compared to a net loss of $34.7 million for the same period of 2016.
• Financial Guidance: Sage expects that its existing cash, cash equivalents and marketable securities will fund operating expenses and capital expenditure requirements, based on its current operating plan, into the second quarter of 2018.

Long trade : SAGE +25% (6/17)

 

SAGE Therapeutics (SAGE) reports Phase 2 Brexanolone clinical data

  

monthly

SAGE Therapeutics reports Phase 2 Brexanolone (SAGE-547) clinical data published in The Lancet:

Co announced that The Lancet has published results from a Phase 2, double-blind, randomized and placebo-controlled study of brexanolone (SAGE-547) in women with severe postpartum depression.

• The study found that treatment with brexanolone resulted in a clinically meaningful and statistically significant mean reduction in the 17-item Hamilton Rating Scale for Depression total score, a common measure of depression severity, that began at 24 hours and was maintained at similar magnitude until the 30-day follow-up.
• Brexanolone was well-tolerated in this study with no observations of deaths, serious adverse events or discontinuations.
• Overall, fewer patients who received brexanolone experienced adverse events compared with placebo (4 of 10 on brexanolone and 8 of 11 on placebo).