Zuranolone shows improvements in symptoms in PPD and MDD patients
CAMBRIDGE, Mass., Oct 17: Sage Therapeutics, Inc. (Nasdaq: Sage) and Biogen Inc. (Nasdaq: BIIB) has presented additional data from the Phase 3 SKYLARK Study of zuranolone in adult women with postpartum depression (PPD), at the 35th European College of Neuropsychopharmacology (ECNP) Congress, taking place October 15-18, 2022, in Vienna, Austria. This was the first time the SKYLARK Study was presented at a medical congress. Zuranolone is an investigational therapy being evaluated as a once-daily, 14-day oral short course treatment in adults with major depressive disorder (MDD) and PPD.
The SKYLARK Study, as previously reported, achieved the primary and all key secondary endpoints, with study participants demonstrating rapid and significant improvements in depressive symptoms as early as Day 3 that were sustained through Day 45. Women with PPD who were treated with zuranolone 50 mg (n=98) showed a statistically significant and clinically meaningful improvement in depressive symptoms at Day 15, the primary endpoint, compared to placebo (n=97) as measured by a change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score (least-squares mean ±SE: zuranolone 50 mg −15.6 ±0.82 vs. placebo −11.6 ±0.82; [p=0.0007]). The study population was diverse, including approximately 22% Black or African American women and 38% identifying ethnically as Hispanic or Latina women.
In the presentation at ECNP, additional secondary endpoint data demonstrated that a higher proportion of patients in the zuranolone 50 mg arm achieved a HAMD-17 response (≥ 50% decrease from baseline HAMD-17 total score) as compared with the placebo arm at Days 3, 8, 15, 21, and 28 (p5% in the zuranolone 50 mg arm) were somnolence, dizziness, sedation, headache, diarrhea, nausea, urinary tract infection and COVID-19.
Sage Therapeutics and Biogen have initiated a rolling submission of a New Drug Application (NDA) to the US Food and Drug Administration for zuranolone in the treatment of MDD and PPD, and plan to complete the NDA filing in the second half of 2022.
Complications
Postpartum depression (PPD) is one of the most common medical complications during and after pregnancy. 1 PPD can have a serious negative impact on a woman, including significant functional impairment, depressed mood and/or loss of interest in her newborn, and associated symptoms of depression such as loss of appetite, difficulty sleeping, motor challenges, lack of concentration, loss of energy and poor self-esteem. PPD is estimated to affect approximately one in eight women who have given birth in the US or approximately 500,000 women annually. 2
Zuranolone (Sage-217/BIIB125) is a once-daily, 14-day, investigational drug in development for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an oral neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and central nervous system and contributes to regulating brain function. Zuranolone has been granted Fast Track and Breakthrough Therapy Designation for MDD and Fast Track Designation for PPD by the U.S. Food & Drug Administration.
Zuranolone is being evaluated in the LANDSCAPE and NEST clinical development programs. The two development programs include multiple studies examining use of zuranolone in several thousand people with a variety of dosing, clinical endpoints, and treatment paradigms. The LANDSCAPE program includes five studies of zuranolone in people with MDD (MDD201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL Studies). The NEST program includes two placebo-controlled studies of zuranolone in women with PPD (ROBIN and SKYLARK Studies). Additionally, Shionogi completed a Phase 2 study of zuranolone in Japan in people with MDD.
Submission
Sage Therapeutics and Biogen have initiated a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration for zuranolone in the treatment of MDD and PPD, and plan to complete the NDA filing in the second half of 2022. If approved, zuranolone would be the first oral medication specifically indicated to treat PPD.
Sage Therapeutics is a biopharmaceutical company fearlessly leading the way to create a world with better brain health. Our mission is to pioneer solutions to deliver life-changing brain health medicines, so every person can thrive.
As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industry’s most diversified pipeline in neuroscience that will transform the standard of care for patients in several areas of high unmet need.
In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil fuels across the company’s operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.
Various statements in this release concern Sage’s future expectations, plans and prospects, including without limitation our statements regarding: plans for completing the NDA filing for zuranolone in MDD and PPD, and the anticipated timing of such filing; the potential profile and benefit of zuranolone in the treatment of PPD; our belief that the data from the SKYLARK Study support the potential of zuranolone in the treatment of PPD; and other statements as to our mission and goals. These statements constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995.
These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, which could cause actual results to differ materially from those contemplated in these forward-looking statements, including the risks that: we may experience delays or unexpected hurdles in our efforts to complete the NDA submission for zuranolone in MDD and PPD, and we may not be able to complete such filing on the timelines we expect or at all; the FDA may find inadequacies and deficiencies in our NDA for zuranolone, including in the data we submit, despite prior discussions, and may decide not to accept the NDA for filing; even if the FDA accepts the NDA for filing, the FDA may find that the data included in the NDA are not sufficient for approval and may not approve the NDA; the FDA may decide that the design, conduct or results of our completed and ongoing clinical trials for zuranolone, even if positive, are not sufficient for approval in MDD or PPD and may require additional trials or data which may significantly delay and put at risk our efforts to obtain approval and may not be successful; the FDA may not meet expected review timelines for our NDA; other decisions or actions of the FDA or other regulatory agencies may affect our efforts with respect to zuranolone and our plans, progress or results; results of ongoing or future studies may impact our ability to obtain approval of zuranolone or impair the potential profile of zuranolone; unexpected concerns may arise from additional data, analysis or results from any of our completed studies; we may encounter adverse events at any stage that negatively impact further development or the potential or scope of approval or that require additional nonclinical and clinical work which may not yield positive results; the need to align with our collaborators may hamper or delay our development and commercialization efforts or increase our costs.
Treatment
The number of patients with PPD, the unmet need for additional treatment options and the potential market for zuranolone in the treatment of PPD, if approved, may be significantly smaller than we expect; and we may encounter technical and other unexpected hurdles which may delay our timing or change our plans, increase our costs or otherwise negatively impact our efforts to gain approval of zuranolone and to make it available as a treatment option for MDD and PPD or to accomplish other aspects of our mission and goals; as well as those risks more fully discussed in the section entitled “Risk Factors” in our most recent quarterly report with the Securities and Exchange Commission (SEC), as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements.
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to the potential, benefits, safety and efficacy of zuranolone; the potential clinical effects of zuranolone; the clinical development program for zuranolone; clinical development programs, clinical trials and data readouts and presentations for zuranolone; the potential treatment of MDD and PPD; the potential of Biogen’s commercial business and pipeline programs, including zuranolone.
LOS ANGELES: No matter how you look at the numbers, “Halloween Ends” had a good opening weekend.
Touted as the final showdown between Laurie Strode and Michael Myers, the slasher pic earned $41.3 million in ticket sales from 3,901 theaters in North America, according to studio estimates Sunday. It’s the first film to open higher than $40 million since “Nope” debuted in July and it surpassed its production budget, which has been reported to be between $20 and $30 million. Including international showings, it boasts a global total of $58.4 million.
“We are extraordinarily excited that Blumhouse once again delivered an incredible film and another No. 1 opening,” said Jim Orr, Universal’s head of domestic distribution. “Jamie Lee Curtis had audiences across North America engaged and terrified.”
The film also renewed an evergreen debate about day-anddate movie releases and some in Hollywood are wondering whether it could have been even bigger if it hadn’t debuted simultaneously on Peacock, NBC Universal’s streaming service.
Going into the weekend, some analysts had pegged “Halloween Ends” for an opening in the $50 to $55 million range. “Halloween Kills,” the previous installment in the David Gordon Green-directed “Halloween” trilogy,” opened day-and-date last year and still grossed $49 million on opening weekend.
Green’s first “Halloween,” by contrast, debuted to $76.2 million in 2018. But that was pre-pandemic, theatrical release only and the highly anticipated revival of a beloved franchise with good reviews. His subsequent “Halloween” films were more divisive among critics and fans, however. “Kills” had a 39% Rotten Tomatoes score while “Ends” has a 40% and still opened over $40 million.
“The day-and-date model was put to the test again, but I think this is a mandate in favor of the movie theater,” said Paul Dergarabedian, the senior media analyst for Comscore. “Audiences had the option to watch it at home but they chose to go to the theater.”
Many studios experimented with day-and-date releases during the second year of the pandemic to varying results, but 2022 has seen most returning to traditional theatrical-first releases — especially for their most valuable brands and franchises.
Still, it triggered a self-proclaimed “rant” from filmmaker Christopher Landon, who tweeted this weekend that he felt his horror film “Freaky” was hurt by its simultaneous release in theaters and streaming in November 2020.
“Stop doing this. Please. It doesn’t work. Studios: stop gambling with filmmakers and their movies to try and prop up your fledgling streaming services,” Landon wrote on Twitter. “I begged the studio not to do this... We got hosed.”
Though there was likely some financial impact on “Halloween
Ends,” it’s hard to glean exactly how much money was left on the table with the release. Peacock is notably smaller than many of its streaming competitors, with 13 million paid subscribers reported at the end of July. Studios also rarely release specific streaming data.
“Smile,” meanwhile, has continued to defy horror-movie odds with another strong weekend. Paramount’s original thriller added $12.4 million, bringing its domestic total to $71.2 million after three weeks.
Dergarabedian noted that it’s rare two have two R-rated horror movies at the top of the box office charts. (AP)