Amylyx Sheds More Light on Relyvrio’s Late-Stage Trial Failure in ALS

 Amylyx Pharmaceuticals on Tuesday unveiled more data from the Phase III PHOENIX study, providing additional context on the recently announced failure of its now-withdrawn amyotrophic lateral sclerosis drug Relyvrio (sodium phenylbutyrate and taurursodiol).

Amylyx first announced that Relyvrio failed the Phase III PHOENIX trial in March 2024, though the company did not reveal specific data from the trial then. The data presented on Tuesday at the 2024 American Academy of Neurology (AAN24) annual meeting showed that at 48 weeks patients who received Relyvrio saw a 14.98-point drop in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), a validated tool that measures the severity of amyotrophic lateral sclerosis (ALS) including the progression of disability and respiratory impairment.

In the late-stage trial, those patients in the placebo arm saw a 15.32-point decrease in scores from baseline. The resulting treatment effect was 0.343, which was in favor of Relyvrio, though not significantly with a p-value of 0.667.

Relyvrio also failed its secondary endpoints. After 48 weeks of follow-up, Amylyx’s drug outperformed placebo by 2.02 points in terms of slow vital capacity and by 1.41 points in the Amyotrophic Lateral Sclerosis Assessment Questionnaire. Both treatment effects fell short of statistical significance. Subgroup analyses likewise did not spot signals of significant efficacy.

As of the AAN24 annual meeting, overall survival data had not yet matured, according to Amylyx. PHOENIX will continue to collect data in this regard.

Amylyx co-CEO Joshua Cohen told Endpoints News that the company is still trying to figure out what caused the failure. “Might there be certain biomarkers, might there be certain biological differences, or otherwise? Or is it just statistical chance? I think all of those are possibilities and things we want to keep learning more about.”

Relyvrio is a combination of two compounds: sodium phenylbutyrate and taurursodiol. Its exact mechanism is still unknown but it is believed to reduce endoplasmic reticulum stress and mitochondrial dysfunction, improving cellular function and lowering cell death. The FDA approved Relyvrio in September 2022.

Prior to Relyvrio’s approval, Cohen and co-CEO Justin Klee pledged that Amylyx would pull the drug from the market if its late-stage results fell flat. “The commitment we made at the advisory committee meeting is we’ll do what’s right for patients,” Klee said at the time.

The CEOs made good on their promise earlier this month, when they voluntarily withdrew Relyvrio from the U.S. and Canadian markets. Reeling from the failure of PHOENIX, Amylyx also instituted a sweeping restructuring plan that saw 70% of its workforce laid off.

https://www.biospace.com/article/amylyx-sheds-more-light-on-relyvrio-s-late-stage-trial-failure-in-als/

Sage Axes Parkinson’s Program for Dalzanemdor After Phase II Flop

 Sage Therapeutics faced another disappointment on Wednesday as the company’s oral drug candidate dalzanemdor stumbled in a Phase II trial and is scrapping its Parkinson’s disease program. The announcement resulted in a 19% drop in Sage’s stock price in Wednesday's premarket trading, according to Seeking Alpha. 

In the Phase II PRECEDENT study, 86 patients with Parkinson’s disease with mild cognitive impairment were enrolled and randomized to receive the oral drug or placebo. Dalzanemdor, an investigational drug in development for cognitive disorders associated with NMDA receptor dysfunction, did not demonstrate a significant difference in the Wechsler Adult Intelligence Scale Fourth Edition-IV (WAIS-IV) Coding Test score compared to placebo at day 42. 

Overall, the drug was found to be safe in the mid-stage trial but did not show any meaningful differences over placebo in any of the exploratory endpoints, including a cognition test. Based on the results, Sage said the company “does not plan any further development of dalzanemdor” in Parkinson’s. 

However, the candidate will continue in Phase II studies in Huntington’s disease and another in mild cognition impairment and mild dementia in Alzheimer's disease. Topline results for the studies are expected in mid-2024 and late 2024, respectively. 

While “disappointed” by the PRECEDENT study, Sage CEO Barry Green said in a statement that "these results do not necessarily predict results with dalzanemdor in other neurodegenerative conditions.” Green also clarified that although it is targeting the cognitive impairment associated with these conditions, the underlying pathophysiology between the diseases is distinct. 

Wednesday’s announcement is the latest setback for Sage. 

In August 2023, the company laid off 40% of its staff—around 188 people—after the FDA rejected the major depressive disorder indication for zuranolone. The Biogen-partnered oral medication was approved only in postpartum depression (PPD), the smaller of the two markets the companies had hoped for and is now branded for the indication as Zurzuvae. It's the second PPD drug approved for Sage, the first being an intravenous injection. 

https://www.biospace.com/article/-sage-axes-parkinson-s-program-for-dalzanemdor-after-phase-ii-flop-/

Lilly Eyes Zepbound Label Expansion After Clearing Phase III Sleep Apnea Study

 Eli Lilly on Wednesday released topline data from the Phase III SURMOUNT-OSA study, which showed that its top-selling weight-loss drug Zepbound (tirzepatide) substantially improved obstructive sleep apnea symptoms in patients.

The pharma will submit these data to the FDA and other global health regulatory agencies by mid-year, according to Lilly’s announcement. Tirzepatide has previously earned the FDA’s Fast Track designation for moderate-to-severe obstructive sleep apnea (OSA).

More than 20 million adults in the U.S. suffer from moderate-to-severe OSA and the vast majority of these cases are undiagnosed and thus untreated, Jeff Emmick, senior vice president of product development at Lilly, said in a statement.

If approved in this indication, tirzepatide could address this unmet medical need, Emmick added, noting that “while there are pharmaceutical treatments for the excessive sleepiness associated with OSA, tirzepatide has the potential to be the first pharmaceutical treatment for the underlying disease.”

SUMOUNT-OSA is a randomized, double-blinded and placebo-controlled study of 469 participants with OSA and obesity. The trial was divided into two main parts: the first focused on patients who were unable or unwilling to use positive airway pressure (PAP), while the second included those who were on and planned to stay on PAP during the duration of the study.

At 52 weeks, patients in the first part of the study saw a mean reduction of 27.4 events per hour in the apnea-hypopnea index (AHI), which measures OSA severity and refers to how many times the patient’s breathing is restricted or blocked per hour of sleep. In placebo counterparts, AHI dropped by 4.8 events per hour.

A similar trend was reported in the second part of the study, with tirzepatide-treated patients reaching a mean AHI reduction of 30.4 events per hour while placebo comparators only showing an average decrease of 6.0 events per hour.

In both parts of the study, tirzepatide treatment triggered greater weight loss versus placebo.

In terms of safety, tirzepatide’s adverse event profile in SURMOUNT-OSA was consistent with what had been established in prior trials. The most common side effects were gastrointestinal in nature and were mild to moderate in severity.

Wednesday’s readout adds to the ever-expanding list of diseases that GLP-1 receptor agonists appear to be effective against.

Last month, the FDA approved Novo Nordisk’s Wegovy (semaglutide) to lower the risk of cardiovascular death, heart attack and stroke in overweight and obese adult patients with cardiovascular disease. A few days earlier, Novo released data from the Phase III FLOW study showing that semaglutide can also significantly preserve kidney health in type 2 diabetes patients with chronic kidney disease.

In February 2024, Boehringer Ingelheim’s obesity hopeful survodutide demonstrated strong potential for metabolic dysfunction-associated steatohepatitis in a Phase II study.

https://www.biospace.com/article/lilly-eyes-zepbound-label-expansion-after-clearing-phase-iii-sleep-apnea-study-/

Sage cut to Underperform from Neutral by B of A

 Target to $14 from $24

https://finviz.com/quote.ashx?t=SAGE&p=d

INVO stock is up alongside earnings results

 Invo Bioscience (NASDAQ:INVO) stock is rocketing higher on Wednesday alongside its earnings report for the fourth quarter of 2023.

The healthcare services fertility company reported a net loss of $2 million during the quarter. That’s an improvement over its net loss of $2.8 million from the same period of the year prior.

Invo Bioscience reported revenue of $1.38 million for Q4 2023, a massive 397% increase over its Q4 2022 revenue of $278,142.

Invo Bioscience CEO Steve Shum said the following in the earnings report:

“During 2023, our revenue increased to more than $3.0 million, a 267% increase from the previous year, and included approximately 4.5 months of revenue from our Wisconsin revenue. In total, revenue from all clinics, inclusive of both those accounted for as consolidated and under the equity method, was more than $4.3 million.”

https://investorplace.com/2024/04/why-is-invo-bioscience-invo-stock-up-85-today/

Vanda Pharmaceuticals Adopts Limited Duration Stockholder Rights Plan

 Vanda Pharmaceuticals Inc. ("Vanda" or the "Company") (Nasdaq: VNDA) today announced that its Board of Directors (the "Board") has adopted a limited duration stockholder rights plan (the "Rights Plan") to protect stockholder interests and maximize value for all stockholders. The Rights Plan is effective immediately.

The Board adopted the Rights Plan in response to the unsolicited acquisition proposal made by Future Pak, LLC ("Future Pak") on April 1, 2024. The Board, in consultation with its independent financial and legal advisors, consistent with its fiduciary duties, carefully reviewed the unsolicited acquisition proposal and concluded that it is not in the best interests of the Company and its stockholders, as it significantly undervalues the Company in light of its robust clinical development pipeline, expanding commercial presence, significant cash balance and long-term future growth prospects.

The Rights Plan is intended to enable stockholders to realize the full value of their investment in Vanda and will reduce the likelihood that any entity, person or group gains control of the Company through open-market accumulation without paying all stockholders an appropriate control premium or providing the Board sufficient opportunity to make informed judgments and take actions that are in the best interests of all stockholders. The Rights Plan applies equally to all current and future stockholders and is not intended to deter offers or preclude the Board from considering offers that are fair and otherwise in the best interest of the Company's stockholders.

https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-adopts-limited-duration-stockholder-rights-plan-302119627.html

Jewish student suspended for using ‘fart sprays’ during anti-Israel protest sues Columbia

 A Jewish Columbia University student claims he was improperly suspended for discharging two “novelty fart sprays” during a campus anti-Israel rally — arguing the substances were “non-toxic” and his actions were harmless, a lawsuit says.

The student, named “John Doe” in court papers, sprayed gag gifts called “Liquid Ass” and “Wet Farts” that he bought on Amazon for $10.99 into the air and not at any particular person during the Jan. 19 protest, the lawsuit, obtained by The Post, claims.

“[The] plaintiff’s actions were a harmless expression of speech to demonstrate discontent with the pro-Hamas pro-Palestine message through the use of a gag gift, and nothing further,” the lawsuit says.

Following the rally, members of the suspended university groups Students for Justice in Palestine and Jewish Voice for Peace claimed that two unknown men approached them outside the Low Library and sprayed an unknown, smelly chemical that caused them to experience headaches, fatigue, and nausea, according to reports.

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Two students at the rally were seen spraying an unknown smelly chemical into the air.@itslaylas/X
Students then described the scent as “raw sewage” and “dead mouse” and said the two men responsible seemed “especially aggressive” toward students holding up signs saying “Jews for ceasefire,” whom they called “self-hating Jews.”

The student, who is a former member of the Israeli military, was suspended for a year and a half following the smelly stunt, his lawyer Jeff Lichtman said in a statement to The Post.

“As a result of Columbia’s flawed and biased investigation and adjudication process, Plaintiff was found responsible for disruptive behavior, harassment, and endangerment, and sanctioned to suspension from the University, forever marring his educational file with an improper finding of responsibility,” the lawsuit reads.

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Columbia suspended the student for a year and a half following the incident.Getty Images

Columbia charged the plaintiff with disruptive behavior, harassment, and endangerment and suspended them for a year and a half, the lawsuit, first reported by Columbia’s student newspaper, reads.

The lawsuit accuses Columbia of a breach of contract, claiming the university violated Title VI of the Civil Rights Act of 1964, New York Executive Law, and New York Civil Rights Law, and New York City Administrative Code.

The suit was filed one day before Columbia President Minouche Shafik is expected in Washington DC for a hearing on the university’s troubles combatting antisemitism on campus.

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Students reported the putrid smell following the march, with some filing formal complaints with the school.@ColumbiaSJP/X

The filing alleges that the student received death threats on social media and was forced to leave his apartment and “distance himself from loved ones.”

“Students have doxed Plaintiff on social media and also created fake FBI ‘wanted’ posters with Plaintiff’s face stating Plaintiff is ‘armed and dangerous,’ creating a hostile environment for Plaintiff and creating a grave safety risk if Plaintiff were to return to campus,” the lawsuit claims.

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The student claims in the suit that they have received death threats ever since the protest.SARAH YENESEL/EPA-EFE/Shutterstock

Students who filed reports with campus public safety following the incident allegedly declined medical evaluation, counseling and psychological services, according to the lawsuit.

“To date, there has been no medical or physical evidence to support the assertions of any of the students that claimed they were harmed and/or impacted by the spray,” the lawsuit reads. “Indeed, the spray is harmless, non-toxic, and can be purchased by anyone on Amazon.”

In the wake of the alleged attack, Columbia’s student newspaper spoke to dozens of students and found 18 reported the sour smell during or after the protest, 10 reported symptoms including burning eyes, headaches, and nausea — with three having sought medical attention — and eight reported damage to their personal belongings.

https://nypost.com/2024/04/17/us-news/jewish-columbia-student-sues-university-following-pro-palestine-march/