FDA Cautions Against Using OTC Products to Remove Skin Spots, Moles

 Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the US Food and Drug Administration (FDA). The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include "skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment," according to the alert, which adds that the agency has received reports of people "who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. "

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, DC, who notes that bloodroot is another ingredient found in these products.

Friedman explained that using these products without the supervision of a healthcare provider can create a chemical burn in the skin, leading to scarring. He's treated patients for open wounds and infected ulcers caused by these products. "Over my career, I've seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms," he told Medscape Medical News.

Another concern is that these spots on the skin are often the only sign of a serious issue — cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer — effectively killing the canary in the coal mine.

There's a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. "If people aren't going to a dermatologist to be properly diagnosed and properly managed, they're going to cause more harm by thinking that they've taken care of a problem," he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you'll be healed in no time.

Anyone who has experienced an adverse event with one of these products, and healthcare professionals, should report cases to the FDA's MedWatch Adverse Event Reporting Program.

https://www.medscape.com/viewarticle/975373

Positive Topline Results for Novel Probiotic in Autism

 Scioto Biosciences has announced positive topline results from their phase 1b trial evaluating the novel probiotic SB-121 (Lactobacillus reuteri with dextran microparticles and maltose) in individuals with autism spectrum disorder (ASD).

The trial represents the first clinical validation of the company's proprietary Activated Bacterial Therapeutics (ABT) platform for delivering "best-in-class, live therapeutic bacteria to the gut," the company noted in a news release.

"This study is an important milestone in the microbiome field, particularly as it relates to the gut-brain axis," Joe Trebley, PhD, founder and CEO of Scioto, said in the release.

"Gastrointestinal disorders are common in people with autism, and we think this product will have a very enviable safety profile," Trebley told Medscape Medical News.

Compelling Data?

Neurologic and gastrointestinal disorders often coexist. Recent evidence suggests a bacterial imbalance in the gut may be associated with, precede, or exacerbate core symptoms of autism.

This first-in-human study of SB-121 was a randomized, double-blind, placebo-controlled, 28-day daily-dose crossover study that evaluated the safety and tolerability of the novel product in 15 people aged 15 to 45 years who had been diagnosed with ASD.

Results showed that SB-121 was safe and well tolerated, which was the primary goal of the phase 1b trial.

The most common adverse events (AEs), irrespective of treatment group, were abdominal pain, vomiting, and diarrhea. Most AEs were mild, and none were serious or severe. No participant discontinued the trial because of AEs.

The study provides preliminary evidence of SB-121-associated improvements in the Vineland-3 adaptive behavior assessment and in objective measures of eye tracking, the company reported.

"Looking at some of the secondary endpoints, the Vineland and also the objective measures, we think we have a really compelling dataset," Trebley said.

Craig Erickson, MD, director at the Kelly O'Leary Center for Autism Spectrum Disorders, Cincinnati Children's Medical Center, Ohio, served as principal investigator for the trial.

The fact that the study enrolled "very rapidly [is] a testament to the unmet medical need and patient/caregiver interest in potentially safe, well tolerated, and effective medicines in this field," Erickson said in the release.

The company plans to publish full results of the phase 1b trial and will launch a phase 2 study sometime later this year or in early 2023.

https://www.medscape.com/viewarticle/975389

CMS Slaps First Hospitals With Fines for Lack of Price Transparency

 This week, CMS handed down their first penalties to two hospitals in Georgia for failing to comply with the price transparency law that went into effect Jan. 1, 2021.

Northside Hospital Atlanta in Sandy Springs and Northside Hospital Cherokee in Canton were both fined for a lack of readily available standard charges for hospital services online, despite warnings.

As part of the Hospital Price Transparency Final Rule, items and services like supplies, room and board, and medical procedures must be posted online, in one machine-readable file that is "consumer-friendly" (e.g., services grouped together that are normally provided together). The two Northside hospitals had neither machine-readable files published digitally (specifically, their standard charges were not posted in a single file), nor were they in a "consumer-friendly" list.

The hospitals were fined $883,180 and $214,320, respectively, based on the number of days they were noncompliant with the law, and a set amount per hospital bed per day.

Both had previously received warning notices, requests for a "corrective action plan," and received technical assistance calls and emailed recaps from CMS from May 2021 to January 2022, but did not take steps to post online price lists that met the requirements.

According to the letters from CMS to the hospitals, during the technical assistance calls, representatives from the hospital "confirmed that the previous violations had not been corrected and, in fact, the hospital system had intentionally removed all previously posted pricing files."

In 2019, HHS established rules for hospitals to make their pricing more transparent, in an effort to give patients, employers, and clinicians the information to make better decisions about care. According to the final rule, "As healthcare costs continue to rise, healthcare affordability has become an area of intense focus." Making hospital pricing available, they wrote, directly relates to lower healthcare costs.

"CMS expects hospitals to comply with the Hospital Price Transparency regulations that require providing clear, accessible pricing information online about the items and services they provide," said Meena Seshamani, MD, PhD, deputy administrator of CMS and director of the Center for Medicare, in a statement. "This enforcement action affirms the Biden-Harris Administration's commitment to making health care pricing information accessible to people across the country and we are committed to ensuring that consumers have the information they need to make fully informed decisions regarding their health care."

The hospitals are far from alone in their lack of transparency, however. According to a JAMA analysis published this week, among 5,239 hospitals, 13.9% had a machine-readable file, 29.4% had a shoppable display of services and pricing, and 50.9% (2,668 hospitals) had neither. Only a sliver of hospitals -- 5.7% -- had both the machine-readable file and the list of services and prices 6 to 9 months after the rule went into effect.

Furthermore, a review of 1,000 U.S. hospitals by PatientRightsAdvocate.org estimated that only 14.3% of hospitals were fully complying with the transparency rule.

Hospitals in lower-concentration markets, more urban areas, and those with higher per-patient per-day revenue were more likely to be in compliance, the analysis found. Most had posted some standard charges, but 85.7% did not have a complete machine-readable file.

CMS has issued 352 warning notices to hospitals who were out of compliance, and 157 "corrective action plan" requests; 171 hospitals have addressed the citations and closed their cases, according to a CMS spokesperson.

With so many noncompliant hospitals to choose from, it's unclear why CMS chose the Northside hospitals to fine first. CMS did not address this question in their emailed statement, and MedPage Today had not yet heard back from the Northside Hospital system for comment by the time of publication.

Both hospitals must pay the penalty within 60 days, but can appeal the civil monetary penalty decision by requesting a hearing within 30 days. If they don't pay, the noncompliance fees will continue to accrue until the hospital corrects their pricing information and notifies CMS.

https://www.medpagetoday.com/special-reports/exclusives/99176

Caribou's allogeneic CAR-T hit by durability doubts as half of patients relapse

 Caribou Biosciences is nursing a hangover. Weeks after celebrating a 100% overall response rate, the CRISPR biotech has revealed 50% of patients relapsed within six months of receiving its allogeneic CAR-T cell therapy, sending shares into a sudden 13% dive that largely erased earlier gains.

Durability has emerged as a sectorwide issue for developers of allogeneic CAR-Ts, with Allogene, CRISPR Therapeutics and Precision Biosciences all seeing significant numbers of cancer patients relapse in the six months after treatment. Caribou has removed the PD-1 receptors from its anti-CD19 candidate, CB-010, in an attempt to reduce CAR-T cell exhaustion and maintain high anti-tumor activity for a longer duration.

The non-Hodgkin lymphoma results from the phase 1 Antler trial, presented at the European Hematology Association (EHA) congress, raise questions about the impact of Caribou’s work to increase durability. As of May 13, three of the six complete responders had relapsed. 

A diffuse large B- cell lymphoma patient relapsed at Month 3. The two other relapses, in patients with mantle cell lymphoma and follicular lymphoma, happened at Month 6. Two of the three patients with ongoing responses were at or approaching the six-month mark as of the data cutoff. The other responder was approaching, and has now passed, the 12-month mark.

The relapses overshadowed other, more encouraging aspects of the data, causing shares in Caribou to fall 13% to around $7.60 in premarket trading. The initial complete response rate rose after the pre-EHA data, climbing from four out of five in the original analysis to six out of six in the poster presentation. 

Caribou achieved that 100% complete response rate at the starting dose of 40 million CAR-T cells. Safety looks good so far. One patient suffered grade 3 immune effector cell-associated neurotoxicity syndrome that resolved in 39 hours, but none of the patients experienced graft-versus-host disease or grade 2 or greater cytokine release syndrome (CRS). Two patients had grade 1 CRS. 

Based on the data, Caribou has begun enrolling patients at the second dose level, 80 million CAR-T cells. Doubling the dose could drive longer-lasting responses, enabling Caribou to differentiate itself from the rest of the allogeneic CAR-T space and renew confidence in its approach for increasing durability.

SVB Securities came down on the side of the "bulls" on the "Cari-boo" debate, pointing to the low dose with room to escalate and the favorable complete response rate at six months. The Antler study is also "early but competitive," the firm noted. 

"The efficacy signal despite a low dose and reasonable safety paint a mosaic that for us supports dosing up as the strategy most likely to produce the best profile for an eventual regulatory filing," SVB Securities wrote. 

https://www.fiercebiotech.com/biotech/hangover-caribous-allogeneic-car-t-hit-durability-doubts-half-patients-relapse

Alpha Tau: FDA Approves IDE to Initiate Multi-Center Pivotal Carcinoma Study

 Alpha Tau Medical Ltd. (Nasdaq: DRTS and DRTSW), ("Alpha Tau" or the "Company"), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT™, announced today that the U.S. Food and Drug Administration (FDA) has conditionally approved the Company's Investigational Device Exemption (IDE) application to initiate its multi-center pivotal study for the treatment of recurrent cutaneous Squamous Cell Carcinoma (SCC) using the Alpha DaRT.

https://finance.yahoo.com/news/alpha-tau-announces-fda-approval-131000328.html

U.S. House Votes to Give FDA More Power Over Accelerated Approvals

 On Wednesday, the House of Representatives voted on a bill that would give the U.S. Food and Drug Administration more power to ensure biopharma companies run large follow-up trials to confirm accelerated approvals. The bill must be passed by September, or the FDA will face funding gaps.

Over the last couple of years, the use of accelerated approvals has received more scrutiny. Typically, accelerated approvals are granted to drugs with a high unmet need and require the biopharma companies to conduct post-marketing studies to determine if the drugs are as effective as they appeared to be in earlier trials. Often, these accelerated approvals are based not on clinical efficacy, but on biomarkers indicating physiological improvement.

The now-classic example is Biogen’s Aduhelm (aducanumab) for Alzheimer’s disease. The drug was approved on the basis that it cleared beta-amyloid plaques, not on improving cognition or memory. The clinical trials that Aduhelm’s approval was based on gave inconsistent and complex data that suggested at the highest dose, the drug might slow the progression of the disease.

In March 2021, BioSpace noted the FDA appeared to be cracking down on accelerated approvals, due to a trend of accelerated approvals being rescinded and unexpected rejections. It wasn’t clear if this was related to a COVID-19-related backlog or potentially, the agency’s lack of a permanent commissioner. At the time, Dr. Janet Woodcock, M.D., was the interim commissioner.

Examples of accelerated approvals that were rescinded include Merck voluntarily withdrawing Keytruda for metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other previous line of therapy. Only a week later, AstraZeneca withdrew its own checkpoint inhibitor, Imfinzi, in bladder cancer over a similar response. The Imfinzi accelerated approval was to be confirmed by the Danube study but did not hit the overall survival endpoints compared to the standard of care.

Of accelerated approvals, companies have voluntarily withdrawn 28. The FDA has only pulled one.

House members voted 392-28 to pass H.R. 7667, which would set a $1.15 billion base fee for human prescription drugmakers for the fiscal year 2023. It would overhaul the accelerated approval process and include provisions for improving clinical trial diversity.

It is a major step required to reauthorize the FDA’s user fees it receives from drug and medical device companies for fiscal years 2023 through 2027. The current authorization will expire on September 30, 2022. Congress hopes to finalize the new package before the August recess.

In terms of accelerated approvals, the package passed by the House allows the FDA to remove any drugs from the market that received accelerated approval if they don’t demonstrate a clinical benefit. Accelerated approvals typically require companies to run confirmatory clinical studies, but they are often given long periods of time to do so.

For example, Sarepta Therapeutics’ Exondys 51 (eteplirsen) received accelerated approval for Duchenne muscular dystrophy (DMD). It was required to conduct a two-year, randomized controlled trial to verify the drug’s benefits. The confirmatory trial isn’t expected to wrap until 2026, a full 10 years since it was first approved.

A study by Evaluate Vantage in 2021 found that of 23 accelerated approvals granted from 2010 to 2020 in non-oncology drugs, only four had converted to full approvals by way of clinical confirmation. And those took an average of 3.5 years to do so.

Woodcock herself recently told the Wall Street Journal, “Accelerated approval has really proved itself as a very effective tool. People pick out the failures, but when we did accelerated approval, we said there would be more uncertainty. If accelerated approval had the same success rate as regular approval, we wouldn’t be doing anything special at all.”

One of the aspects of the new bill is the FDA would have the legal authority to require that confirmatory trials are underway before granting accelerated approval. It would also decrease the number of steps the agency requires to get the drug withdrawn. The bill would also allow the agency to set enrollment targets for clinical trial participants, protocols and milestones, including the date the trials would target for completion.

https://www.biospace.com/article/fda-nears-having-more-power-to-pull-accelerated-drugs/

ADC: Results from Pivotal Phase 2 Trial of Camidanlumab Tesirine in Hodgkin Lymphoma

 Overall response rate of 70.1% and complete response rate of 33.3% in heavily pretreated patients; median duration of response of 13.7 months

Safety profile substantially consistent with prior findings

Preparing for potential submission of a Biologics License Application to the FDA

Cami data and diffuse large B-cell lymphoma posters to be presented today at the European Hematology Association 2022 Hybrid Congress

https://finance.yahoo.com/news/adc-therapeutics-announces-results-pivotal-070000963.html