FDA sets August date for Adaptimmune’s sarcoma drug verdict

 The FDA is due to decide by 4th August whether to approve Adaptimmune’s engineered T-cell therapy for advanced synovial sarcoma, afamitresgene autoleucel (afami-cel), after a priority review.

If the biologics license application (BLA) is approved, afami-cel will become the first engineered T-cell therapy for solid tumours and the first effective treatment option for advanced synovial sarcoma in more than a decade, according to the Anglo-American company.

Synovial sarcoma is a rare soft tissue sarcoma, one of around 50 that appear in fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues that can be hard to diagnose and treat. The cancer accounts for around 5% to 10% of all soft tissue sarcoma types with around 13,400 new cases in the US every year, mainly in people aged 30 or less. It tends to metastasise easily to other tissues and has a five-year survival rate of just 20% if diagnosed at an advanced stage.

In the pivotal SPEARHEAD-1 trial, afami-cel demonstrated an objective response rate (ORR) of around 39% among heavily pre-treated patients with advanced synovial sarcoma, along with a 17-month median overall survival (OS) that Adaptimmune says represents a “significant advance” in treatment for this patient population.

Typically, ORRs for second-line therapies have ranged between 14% and 18%, with an OS range of between nine and 12 months, but around 70% of patients who responded to afami-cel in the study are alive two years after treatment, according to the company.

First-line therapy for synovial sarcoma generally relies on anthracycline-based chemotherapy with or without ifosfamide, and the last drug approved for second-line therapy was GSK’s kinase inhibitor Votrient (pazopanib) in 2012.

Eli Lilly’s anti-PDGFR-α antibody drug Lartruvo (olaratumab) was granted accelerated approval in 2016 as an option for newly diagnosed patients with soft tissue sarcomas who could not be treated with chemo, but was pulled from the market in 2019 after it failed a post-marketing confirmatory study.

$400m franchise

Adaptimmune has estimated that MAGE-A4-targeted afami-cel and a companion cell therapy for synovial sarcoma and myxoid/round cell liposarcoma (MRCLS) called letetresgene autoleucel (lete-cel) collectively have the potential to make sales of around $400 million a year with upside if they expand into earlier lines of therapy and additional sarcoma types.

Lete cel is a NY-ESO-targeting therapy, partnered with GSK, that recently generated positive results in the pivotal IGNYTE-ESO as a third-line treatment, with full data due to be presented in the third quarter.

“The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for people with synovial sarcoma,” commented Adrian Rawcliffe, Adaptimmune’s chief executive,

“Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-cel – the first engineered T-cell therapy on the market for a solid tumour cancer,” he added.

https://pharmaphorum.com/news/fda-sets-date-adaptimmunes-sarcoma-drug-verdict

'Latest COVID-19 Shots 54-57% Effective for Adults'

 The updated 2023-2024 COVID-19 vaccine was approximately 54% effective against symptomatic SARS-CoV-2 infection in adults, and was also effective against the JN.1 variant, which became predominant in January, CDC researchers said.

Overall, vaccine effectiveness against symptomatic COVID was 57% for people ages 18 to 49 years and 46% for people ages 50 and older, reported Ruth Link-Gelles, PhD, of the CDC's National Center for Immunization and Respiratory Diseases, and colleagues in the Morbidity and Mortality Weekly Reportopens in a new tab or window.

The updated vaccine is a monovalent XBB.1.5-derived vaccine, and there have been few estimates regarding its effectiveness, the authors noted. This study is the first to look at the vaccine's effectiveness against symptomatic COVID caused by the JN.1 variantopens in a new tab or window, a derivative of BA.2.86.

The data came from the CDC's Increasing Community Access to Testing program that provided no-cost SARS-CoV-2 nucleic acid amplification tests (NAAT) to uninsured people at participating CVS and Walgreens pharmacies from Sept. 21, 2023 to Jan. 14, 2024.

Vaccine effectiveness was 58% among those who received testing 7 to 59 days after receiving the updated vaccine, and 49% among those who received testing 60 to 119 days after receipt.

In a subanalysis, the researchers also looked at spike gene amplification results from reverse transcription-polymerase chain reaction (RT-PCR) COVID tests to differentiate XBB lineages from JN.1 and other Omicron BA.2.86 lineages.

For those who had received the updated vaccine 60 to 119 days earlier, vaccine effectiveness was 49% for tests indicating infection with JN.1 lineages, and 60% for tests indicating infection with non-JN.1 lineages.

"Whereas the goal of the U.S. COVID-19 vaccination program is to prevent severe disease, vaccine effectiveness against symptomatic infection can provide useful insights into protection early after introduction of updated vaccines and during the emergence of new lineages," Link-Gelles and colleagues wrote.

The study only looked at data through 119 days since vaccination -- a relatively brief period of time, the authors pointed out. "Waning of effectiveness is expected with additional elapsed time since vaccination, especially against less severe disease," they noted.

In September 2023, the CDC's Advisory Committee on Immunization Practices (ACIP) recommendedopens in a new tab or window that everyone 6 months of age and older get the 2023-2024 updated COVID vaccine.

This analysis looked at 9,222 NAAT COVID test results over the study period among people with COVID-like symptoms. Most people tested were women (61%), about 40% were white, 30% were Hispanic or Latino, and 16% were Black or African American.

Of available NAAT tests, 36% were positive for SARS-CoV-2. The researchers calculated vaccine effectiveness by comparing odds of receipt versus nonreceipt of the updated COVID vaccine among those who tested positive (case patients) and those who tested negative (control patients). Of the 1,125 individuals who had received an updated COVID vaccine at least 7 days before testing, 14% were SARS-CoV-2-negative and 9% were positive.

Notably, only 12% of all people tested reported that they had received an updated vaccine dose, and over 26% had never received any COVID vaccine. Sixty percent reported a previous SARS-CoV-2 infection more than 3 months before the current test.

Link-Gelles and team pointed out that vaccination status, previous infection history, and underlying medical conditions were self-reported and subject to bias. Since there is a high prevalence of infection-induced SARS-CoV-2 immunity among adults in the U.S., previous infection was probably underreported and likely provided some protection against repeat infection.

Disclosures

Link-Gelles and co-authors reported no potential conflicts of interest.

Primary Source

Morbidity and Mortality Weekly Report

Source Reference: opens in a new tab or windowLink-Gelles R, et al "Early estimates of updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection attributable to co-circulating Omicron variants among immunocompetent adults -- Increasing Community Access to Testing program, United States, September 2023-January 2024" MMWR 2024; DOI: 10.15585/mmwr.mm7304a2.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/108537

HHS Expands Access to Methadone, Buprenorphine

 As part of a broader overdose prevention strategy, the Biden administration announced changes to decades-old federal rules, which aim to simplify and expand access to addiction treatment in order to save more lives.

Specifically, the final ruleopens in a new tab or window, issued by HHS, makes permanent pandemic-era flexibilitiesopens in a new tab or window that allow eligible patients with an opioid use disorder (OUD) to receive take-home methadone doses. Studies have suggested that take-home doses improve treatment adherence and reduce patients' risk of illicit opioid use, according to a Substance Abuse and Mental Health Services Administration (SAMHSA) press releaseopens in a new tab or window.

"At HHS, we believe there should be no wrong door for people who are seeking support and care to manage their behavioral health challenges, including when it comes to getting treatment for substance use disorder. The easier we make it for people to access the treatments they need, the more lives we can save," said HHS Deputy Secretary Andrea Palm in the press release.

In addition, the administration announced that grant dollars can now be used to buy xylazine test strips, providing one more mechanism for preventing overdose deaths. Xylazine, a veterinary tranquilizer thought to be involved in a growing number of overdose deaths, is approved by the FDA for use in animals, but has not been approved for use in humans. HHS released a specific plan to address fentanyl-laced xylazineopens in a new tab or window in July 2023.

The new final rule also includes the following additional provisions:

• Allows the use of telehealth to initiate treatment for an OUD and to reduce transportation barriers; for treatment with methadone, audio-visual telehealth is allowed, and for treatment using buprenorphine, audio-only technologies are permitted
• Allows nurse practitioners and physician assistants to order medications in opioid treatment programs, where state laws permit such a practice
• Eliminates "stringent admission criteria," which previously restricted eligibility for treatment to those with at least a 1-year history of addiction
• Increases access to "interim treatment" by enabling patients to start medications while waiting for additional services to become available

"While this rule change will help anyone needing treatment, it will be particularly impactful for those in rural areas or with low income for whom reliable transportation can be a challenge, if not impossible," said Miriam E. Delphin-Rittmon, PhD, the HHS Assistant Secretary for Mental Health and Substance Use, who leads SAMHSA, in the press release.

"In short, this update will help those most in need," she added.

Delphin-Rittmon also highlighted SAMHSA's updated "Overdose Prevention and Response Toolkit,opens in a new tab or window" which was released earlier this week and provides guidance on the role of opioid overdose reversal medications, and how to respond to an overdose.

Importantly, in January 2023, the Biden administration also eliminated the X-waiver requirementopens in a new tab or window for clinicians who use medications to treat patients with substance use problems.

The Biden administration aims to invest $83 billion in treatment, which is 42% more than under the Trump administration, according to a White House press releaseopens in a new tab or window.

"Under President Biden's leadership, we have invested more funding and broken more barriers to treatment than any previous administration," noted Rahul Gupta, MD, MPH, director of the Office of National Drug Control Policy. "As a physician who has provided addiction treatment firsthand, I know these actions can mean the difference between life or death."

Bobby Mukkamala, MD, chair of the American Medical Association's Substance Use and Pain Care Task Force, hailed the final rule as a "step in the right direction in the fight against the worsening overdose epidemic." The task force was especially pleased to see the administration's focus on increasing equitable access to care and reducing the stigma around treatment, he said.

"Whether audio-only, video visits, or in-person appointments, physicians provide high-quality, evidence-based care for OUD, including prescribing medication that can save lives," he noted. "Modernizing rules and regulations for prescribing these medications continues to be of paramount importance."

The final rule takes effect April 2, with a compliance date of October 2.

https://www.medpagetoday.com/publichealthpolicy/healthpolicy/108561

What Is Tianeptine and Why Is It in Demand?

 An uptick in adverse events connected to unregulated tianeptine products -- often referred to as "gas station heroin" -- along with the voluntary recall of a popular product have brought renewed attention to the atypical tricyclic antidepressant.

Earlier this week, the company that makes a product called Neptune's Fix issued a voluntary recallopens in a new tab or window of several of its products due to "undeclared tianeptine." The move follows a warningopens in a new tab or window from FDA last November urging consumers not to purchase or use Neptune's Fix products or products with tianeptine, given reports of seizures, loss of consciousness, and death.

So what is tianeptine and why is it becoming so popular?

Daniel Lasoff, MD, emergency medicine physician and toxicologist at University of California San Diego Health, told MedPage Today that the compound "has some opioid receptor activity, which is unusual for a tricyclic antidepressant."

"We've had a pretty large migration away from tricyclic antidepressants as a first-line drug," Lasoff said, noting that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have taken their place.

Some tricyclic antidepressants, such as nortriptyline (Pamelor), imipramine, and amitriptyline are still commonly used, though "those drugs don't typically have any opioid agonism," he said.

Tianeptine was developed in the 1960sopens in a new tab or window and is used in some parts of Europe, Asia, and South America to treat depression and pain. Some brand names include Coaxil, Stablon, and Tatinol.

But in order for tianeptine to ever be used clinically here in the U.S., there would need to be solid research and clinical trials, Lasoff said.

"I don't think it's a particularly effective drug with a good safety profile compared to what's already available out there," he said.

Since tianeptine is not regulated and is easily available in powder, liquid, or capsule form at gas stations and online, its popularity has surged. According to the FDAopens in a new tab or window, there were only 11 total tianeptine exposure cases at poison control centers from 2000 to 2013, but in 2020 alone there were 151 cases.

A recent report from New Jersey's poison control center published in Morbidity & Mortality Weekly Reportopens in a new tab or window highlighted an "uncharacteristic spike" in patients who became critically ill after ingesting contaminated tianeptine products.

Among the 17 patients identified, 14 took products made by Neptune's Fix, Christopher Counts, MD, of Rutgers New Jersey Medical School, and colleagues reported. Thirteen of the 17 patients were admitted to the ICU and seven required intubation. Patients reported symptoms such as tachycardia, hypotension, seizure, and cardiac arrest.

After testing six bottles of the product, the CDC found "variable composition," and some were contaminated with emerging synthetic cannabinoids, they reported.

"It's important for members of the public and healthcare professionals to be aware that readily purchased tianeptine products might be adulterated with synthetic cannabinoid receptor agonists or other drugs and can produce severe adverse effects," the researchers cautioned.

Lasoff also warned that people who buy and use tianeptine products "tend to develop dependency or addiction" and then doctors "see people develop withdrawal syndromes from them."

In a 2023 narrative review of tianeptine's pharmacology and abuse potential published in Pain and Therapyopens in a new tab or window, Amber Edinoff, MD, and co-authors wrote that tianeptine can act as a full agonist at the mu-opioid receptor and "its short half-life can lead to rapid withdrawal, increasing its potential for addiction and misuse."

Reddit has a "quitting tianeptineopens in a new tab or window" forum with more than 5,200 members. Some people share stories of trying to stop using tianeptine while others post about using tianeptine to lessen dependency on other substances, like kratomopens in a new tab or window.

Lasoff said he's heard of both situations, and rather than trading one drug for another, "the smart thing to do would be to use some sort of replacement therapy that is already approved and has good research behind it -- things like buprenorphine or methadone," which both have long half-lives. He also urged fellow doctors to talk to their patients about supplements and substances.

Last month, five members of Congress, including emergency physician Rep. Rich McCormick, MD, (R-Ga.) wrote a letter to FDA commissioneropens in a new tab or window Robert Califf, MD, urging the FDA to issue guidance on tianeptine.

Specifically, they wanted the FDA to research the health effects of using and overusing tianeptine and investigate whether it should be a controlled substance.

A few days after the letter, Rep. Jimmy Panetta (D-Calif.) introduced a bill to Congressopens in a new tab or window to "amend the Controlled Substances Act to provide for the scheduling of tianeptine as a schedule III substance, and for other purposes."

https://www.medpagetoday.com/special-reports/features/108541

Over 500 Arrested In California Human Trafficking Operation

 by Marc Olsen via The Epoch Times (emphasis ours),

A statewide human trafficking crackdown this month netted more than 500 arrests and rescued dozens of people, including juveniles, authorities said Jan. 31 during a news conference in downtown Los Angeles.

The 539 suspects included 40 alleged sex traffickers and 271 alleged “sex buyers,” officials said. Among the rescued were 54 adults and 11 minors, including a 14-year-old girl.

“This week-long operation demonstrates that if you engage in human trafficking activities, harm our children, and destroy lives, there will be absolute consequences, and there is no refuge for predators in the state of California,” Los Angeles County Sheriff Robert Luna said during the press conference in front of City Hall.

The operation was conducted from Jan. 21 to Jan. 27.

It was unclear how many suspects were from Los Angeles, but Mr. Luna described one undercover sting along Holt Avenue in Pomona, about 30 miles east of downtown Los Angeles, that nabbed 12 men on suspicion of soliciting prostitutes.

Mr. Luna also told of a San Diego County incident in which a man approached a teenage girl at an El Cajon mall, urged her to become a model, and gave her a business card.

When she called, she learned the work involved “date sex” at hotels. She told her mother, who called authorities, and the man was arrested.

Mr. Luna said the operation—known as Reclaim and Rebuild—is conducted every January. This year, it included 95 federal, state, and local agencies, including the Los Angeles Police Department and LA County Sheriff’s Department.

Joining Mr. Luna at the news conference was LA County District Attorney George Gascón.

Mr. Gascón told local television station KABC that prosecuting sex traffickers and sex buyers is difficult because victims sometimes are afraid to testify.

https://www.zerohedge.com/political/more-500-arrested-california-human-trafficking-operation

Speaker Johnson says Biden not ‘allowed’ by staff to take action on border

 Speaker Mike Johnson (R-La.) speculated Friday that President Biden’s staff is keeping him from taking executive action to stem the flow of migrants on the southern border.

“He knows that he has the authority. We’ve documented it for him. I’ve read to him the law myself — to the president. Read him the provisions of the law and said, ‘Mr. President, please take action,’” Johnson said on Fox Business on Friday morning.

“I don’t think he’s allowed to do it. I’m not sure Joe Biden is actually making these decisions. I think it’s staff around him, and they’re pushing him to hold the — or to keep the border open,” Johnson said.

Johnson has been pressing Biden for weeks to take executive action on border and migration policy — including by reinstating the Trump-era “Remain in Mexico” policy and restarting construction of the wall on the U.S.-Mexico border — and arguing he does not need new authority from Congress to do so. 

The push comes as Johnson criticizes a deal being crafted by a bipartisan group of senators pairing an increase in Ukraine aid with border and migration policy changes. While the text is not yet out, Johnson said that if the bill’s contents are as reported in the press, it is “dead on arrival” in the House. 

The White House has disputed that Biden can do more through executive authority and accused the Speaker of resisting the Senate border deal and pushing for executive actions — despite previously calling for enactment of other border legislation — for political reasons. Former President Trump has urged Republicans, and Johnson specifically, to reject the Senate border deal.

“Speaker Johnson claimed he believes action should be taken to secure the border. Yet it is House Republicans who are saying they will block an historic bipartisan border security deal supported by President Biden that will deliver much-needed law enforcement hiring and investments in cutting-edge technology to stop fentanyl trafficking,” White House spokesperson Andrew Bates said in a statement earlier this week.

Senate Majority Leader Chuck Schumer (D-N.Y.) said Thursday that the text of the border-Ukraine deal will be released by Sunday.

Johnson, despite his criticism of the reported details, is not completely shutting down the bill.

“The devil is in the details. We’ll check it out,” Johnson said on Fox Business. “I’m not prejudging anything, but I’ve told them the necessary elements of H.R. 2 are what are required to get control of the border. I’ve been consistent, and that’s our standard. We’ll be looking for that.”

https://thehill.com/homenews/house/4444512-speaker-johnson-says-biden-not-allowed-by-staff-to-take-action-on-border/

'Questions linger over cost of OTC birth control pills'

 

Over-the-counter (OTC) birth control pills are on the way, but the potential price for these contraceptives is raising concerns that accessibility may be lost if they aren’t affordable.

Perrigo via AP

Perrigo Company’s Opill birth control pill is set to become available in the first quarter of this year. The company has not disclosed the retail price of the pill, with a spokesperson saying it is committed to making sure its product is “accessible to people who need it.”    Stakeholders hope to avoid a similar situation to when OTC hearing aids became available in 2022. The ultimate cost of the products was much higher than what people would have paid with insurance.    In anticipation of the product hitting retail locations, lawmakers and activists are calling on the federal government to make sure that Opill is affordable for most consumers.     California Gov. Gavin Newsom (D) led other Democratic governors in calling on the Department of Health and Human Services to expand private insurance coverage to OTC products.    “Without coverage that includes low or no out-of-pocket costs, over-the-counter birth control products become much less accessible,” the governors wrote.      Surveys have indicated a large share of reproductive-aged women — about 40 percent — would be willing to pay between $1 and $10 a month, but only 16 percent would pay more than $20 a month.   The steering committee for the Free the Pill campaign called on Perrigo this week to price a 3-month supply of Opill at $15.    “Though we are also advocating for OTC birth control to be fully covered by insurance without a prescription or cost sharing, we know that because US health insurance is often tied to employment, a high retail price could also put Opill out of reach for people who don’t have employer-based insurance,” the group wrote.  https://thehill.com/newsletters/health-care/4445504-price-questions-linger-for-over-the-counter-birth-control-pills/