Regulatory Pathway for a Potential NDA Submission Clarified Following Recent Interactions with the FDA
• FDA Acknowledged that SHIELD I Pre-specified Subgroup Results May Provide Supportive Evidence and Proposed that Current SHIELD II Trial Could Potentially Serve to Complete Clinical Testing for NDA
• FDA Also Recognized that D-PLEX100’s Proposed Indication is for the Prevention of Infection and Has the Potential for Wide Use
The strength and frequency of COVID variants have created a whack-a-mole approach for pharmaceutical companies trying to provide effective pre-exposure protection and therapies for both the general public and immunocompromised individuals. A new variant pops up, and doctors must essentially go back to the drawing board to develop new monoclonal antibodies to counter the new variant effectively.
Tonix Pharmaceutical’s (NASDAQ: TNXP) CEO Seth Lederman, MD told the audience at the 2023 Biotech Showcase earlier this month in San Francisco that a new class of more mutant-resistant pre-exposure antibody therapies for patients at high-risk of Covid-19 is urgently needed and their development is within reach of Tonix’s technology.
For immunocompromised individuals, SARS-CoV-2 is especially a real and dangerous threat. People who are immunocompromised are more likely to get COVID, could be sick for an extended period of time and have higher rates of hospitalization.
Due to these increased comorbidity factors, pharmaceutical companies came out with therapeutic and pre-exposure monoclonal antibody-based medicines for people with higher risk factors. However, with the onslaught of new variants almost all of the monoclonal antibody drugs have become obsolete. Currently, the only monoclonal antibody therapy remaining on the market is EVUSHELDTM, which is the pre-exposure drug that can be taken every six months to help prevent COVID.
“Although four therapeutic monoclonals and one preventative monoclonal were approved under the FDA’s Emergency Use regulations, the four therapeutic monoclonal antibodies are no longer marketed in the U.S. because SARS-CoV-2 variants have rendered them ineffective. Only the single preventative monoclonal remains on the market, Now that remaining antibody drug, EVUSHELD, appears to be nearing the end of its utility because of new variants,” Dr. Lederman said.
Small U.S. Phase 1 trial with newly optimized formulation to confirm favorable safety profile from three previous clinical trials and facilitate Phase 2B development of PH10 as a stand-alone treatment for major depressive disorder
VistaGen Therapeutics, Inc. (NASDAQ: VTGN) a late clinical-stage biopharmaceutical company aiming to transform the treatment landscape for individuals living with anxiety, depression and other central nervous system (CNS) disorders, today announced the first cohort of healthy volunteers has been dosed in its U.S. Phase 1 clinical trial of PH10, the Company’s investigational pherine nasal spray in development for the treatment of major depressive disorder (MDD).
The primary objective of this U.S. single center, randomized, double-blinded, placebo-controlled Phase 1 study is to investigate the safety and tolerability of PH10 in healthy adult subjects (n=12). The study is intended to confirm the favorable safety profile of PH10 established in three previous clinical studies conducted in Mexico, including a published Phase 2A study for the treatment of MDD, as well as facilitate Vistagen’s plans for Phase 2B development of PH10 as a stand-alone treatment for MDD. Vistagen anticipates completion of the study by the end of Q1 2023, with top line results expected before the end of the first half of 2023.
A gynecologist who molested patients during a decades long career was convicted of federal sex trafficking charges Tuesday after nine former patients told a New York jury how the doctor they once trusted attacked them sexually when they were most vulnerable.
A Manhattan federal court jury returned its verdict after deliberating less than a day in the case against Robert Hadden, 64, who worked at two prestigious Manhattan hospitals — Columbia University Irving Medical Center and New York-Presbyterian Hospital — until complaints about his attacks shut down his career a decade ago.
The institutions have already agreed to pay more than $236 million to settle civil claims by more than 200 former patients.
Hadden’s lawyers admitted that their client had sexually abused patients, but they said his guilty plea to charges in state court seven years ago put those crimes behind him.
Prosecutors said federal charges were appropriate because Hadden, of Englewood, New Jersey, enticed women to cross state lines so he could attack them.
Defense lawyers argued that he didn’t know patients were coming from other states, including New Jersey and Nevada.
After the verdict, U.S. Attorney Damian Williams issued a statement in which he called Hadden “a predator in a white coat.”
“For years, he cruelly lured women who sought professional medical care to his offices in order to gratify himself. Hadden’s victims trusted him as a physician, only to instead become victims of his heinous predilection,” he said.
The verdict capped a two-week trial that featured a procession of former patients who described how the doctor questioned them about their personal lives, including their sexual experience, before touching them inappropriately on the breasts or between their legs.
An indictment charged Hadden with sexually abusing patients from 1993 through at least 2012, although a prosecutor noted during a closing argument on Monday that a nurse testified that he was molesting patients in the late 1980s.
“He donned his white coat and took the oath all doctors do to ‘do no harm’ and then he did the exact opposite,” Assistant U.S. Attorney Jane Kim told the jury.
She said he tried to “hide behind his white coat” and the prestige of Columbia University as he won over vulnerable patients before sexually abusing them.
In her closing, defense attorney Kathryn Wozencroft said what some of Hadden’s patients endured at his hands was “disgusting and horrible,” but that his state court convictions covered those crimes.
She argued that the federal charges were inappropriate because they required that Hadden entice his victims to cross state lines when he was unaware in advance of which patients he would treat each day and where they were coming from.
Among former patients who have spoken publicly was Evelyn Yang, whose husband, Andrew Yang, ran unsuccessfully as a Democrat for president in 2020 and for New York City mayor in 2022.
In 2020, she said Hadden sexually assaulted her eight years prior, even when she was seven months pregnant. She had called the sentence in the state case a “slap on the wrist.”
The Associated Press generally withholds the names of sexual abuse victims from stories unless they have decided to tell their stories publicly, which Yang and others have done.
Tofersen, an experimental therapy being developed by Biogen and Ionis for superoxide dismutase 1 (SOD1) ALS will face the FDA’s Peripheral and Central Nervous System Drugs advisory committee on March 22nd.
Biogen is seeking accelerated approval of tofersen based on the use of neurofilament light chain (NfL) as a surrogate biomarker that is reasonably likely to predict clinical benefit.
In July 2022, the FDA accepted the New Drug Application for tofersen under priority review. This, despite the candidate’s failure to meet the primary endpoint in the Phase III VALOR trial.
The adcomm was expected, as the FDA noted it planned to hold one at the time of the NDA approval.
In a statement e-mailed to BioSpace, a Biogen spokesperson said the company could not speculate on the focus of the adcomm. However, it is likely the committee will focus on the validity of neurofilament as a surrogate biomarker in ALS.
Tofersen was originally scheduled to go before the FDA on Jan. 25, 2023, but in October the regulator extended the date to April 25. This was to allow additional time for review based on Biogen’s responses to questions raised by the FDA.
A Controversial History
SOD1-ALS is caused by a mutation in the SOD1 gene. It accounts for up to 20% of familial ALS cases and 2% of all cases. Tofersen, an antisense drug, is thought to reduce the synthesis of SOD1 protein production.
If successful, it would be the first therapy approved for a genetic cause of ALS.
Tofersen first captured the attention of the general public when Lisa Stockman Mauriello sought access to the drug in March 2021. Stockman Mauriello, who had a particularly devastating A5V mutation that typically claims its victims within 12 months, requested access under the Right to Try act. This legislation, signed into law in 2018, allows terminally ill patients to appeal for access to experimental medications that could save or extend their lives.
At the time, VALOR had yet to be completed and Biogen took the position that expanding access outside the confines of the study would not be fair to the placebo cohort.
Biogen opened applications for a compassionate use program on June 25, 2021, and Stockman Mauriello received her first treatment a month later. She succumbed to the disease 11 days after that.
In October 2021, tofersen failed to meet the primary endpoint of change from baseline to week 28 on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). At the time, Biogen pointed to “trends favoring tofersen” across secondary and exploratory measures.
Neurofilament as a Neurodegenerative Biomarker
Eleven months later, Biogen elaborated on these trends with the publication of detailed 12-month data from VALOR in the New England Journal of Medicine. The review included a combined analysis of the trial and accompanying open-label extension study.
The longer-term data showed that earlier initiation of tofersen slowed decline in function and strength in SOD1-ALS patients. Secondly, Biogen reported “substantial lowering” of neurofilament levels, which Timothy Miller, M.D., Ph.D., principal investigator and ALS Center co-director at Washington University School of Medicine, St. Louis interpreted as potentially slowing the underlying disease process.
Biogen will present an overview of this data, which includes the 12-month integrated results from the VALOR study and OLE, the same spokesperson said.
In a previous interview with BioSpace, Kasper Roet, Ph.D., founder and CEO of QurAlis, pointed to the rise of neurofilament as a biomarker in ALS, noting that it had been part of the discussion during the advisory committee meetings for Amylyx’s Relyvrio.
“I think there’s more confidence in the use of that biomarker for ALS, and we have a big need for biomarkers in neurodegeneration,” he said.
ALS isn’t the only indication where neurofilament is gaining traction. In December 2022, Athira Pharma presented biomarker data from the Phase II ACT-AD study showing that its Alzheimer’s disease candidate fosgonimeton caused reductions in both neurofilament and neuroinflammation.
For ALS – and many more neurodegenerative diseases – the upcoming tofersen adcomm is certain to have implications for the use of neurofilament as a surrogate biomarker of efficacy.
https://www.biospace.com/article/biogen-s-sod1-als-drug-to-face-march-22-adcomm/
Cassava Sciences Inc (NASDAQ: SAVA) announced topline Phase 2 results for simufilam, its oral drug candidate for Alzheimer's disease dementia.
Study participants were administered open-label simufilam tablets 100mg twice daily for one year or more. Endpoints were measured at baseline (study entry) and month 12.
In the mild sub-group, ADAS-Cog (cognitive scale) scores improved, from 15.0 (±6.3) to 12.6 (±7.8)
In the moderate sub-group, ADAS-Cog scores worsened, from 25.7 (±9.2) to 30.1 (±13.1). Investors are probably reacting to this.
MMSE scores (cognitive impairment) changed from 21.5 (±3.6) - 20.2 (±6.4).
NPI10 scores (symptom Severity and Distress score) changed from 3.2 (±4.6) to 2.9 (±4.6).
Simufilam 100 mg twice daily was safe and well-tolerated. There were no drug-related serious adverse events.
CSF biomarkers of disease pathology, t-tau, and p-tau181, decreased by 38% and 18%, respectively. CSF biomarkers of neurodegeneration, neurogranin, and neurofilament light chain decreased by 72% and 55%, respectively.
CSF biomarkers of neuroinflammation, sTREM2, and YKL-40, decreased by 65% and 44%.
Cassava Sciences is evaluating simufilam tablets for Alzheimer's disease dementia in two Phase 3 studies.
Most recently, FDA struck off Eli Lilly And Co's (NYSE: LLY) donanemab for early symptomatic Alzheimer's disease due to the limited number of patients. The agency asked for additional data.
New solution scans and compares direct-to-consumer pricing with insurance pricing to give members the best available price
Prescription drug purchases automatically included in members’ deductibles to maximize their benefits
Optum Rx, UnitedHealth Group’s (NYSE: UNH) pharmacy services company, has launched Price Edge, a tool that seamlessly compares available direct-to-consumer pricing for traditional generic drugs with insurance pricing to ensure members always get the lowest prescription drug price. Price Edge is being offered to all Optum Rx clients.
Compared to most direct-to-consumer prescription drug prices, Optum Rx already offers a lower price nearly 90% of the time and Price Edge ensures a competitive consumer price on generic drugs with every transaction. Price Edge scans available prices and automatically provides the lowest available pricing to the member. If there is a lower cost to the member outside of their insurance benefit, Price Edge automatically applies that price.
Unlike other direct-to-consumer pharmacy solutions or cash market pricing, transactions initiated through Price Edge count toward the member’s deductible and out-of-pocket maximum. Plan sponsors also do not incur additional administrative fees for implementing Price Edge and their members automatically access the tool within their plan at no cost. Additionally, by capturing all transactions within the member benefit, Price Edge maintains continuity of safety protocols and safeguards against contraindications between medications.
https://finance.yahoo.com/news/optum-rx-launches-price-edge-140000366.html
