Tobacco companies now have to display signs at retail locations stating health effects of smoking

 The Department of Justice (DOJ) announced this week that tobacco companies in the U.S. will now be required to set up signs in retail locations stating the health risks and effects of cigarettes, following through on a corrective measure issued as part of a lawsuit filed more than 20 years ago.

In 1999, the DOJ filed a lawsuit against several major tobacco companies, accusing them of violating the Racketeer Influenced and Corrupt Organizations Act (RICO). The suit alleged that the tobacco companies had purposely misled the public on the risks of smoking for decades.

A federal judge in 2006 found the companies liable for the alleged RICO violations and ordered the defendants to issue corrective measures, stating that the companies were likely to continue violating RICO going forward without such orders.

However, the tobacco companies challenged this finding in court, delaying the implementation of the ordered measures. The initial decision was ultimately upheld and an agreement between the two parties was reached, with the corrective measures going into effect in 2017.

These corrective measures included issuing statements about the dangers of smoking tobacco in print, online and on major television networks in both English and Spanish.

The measure announced this week is the final remedy that has yet to be issued as part of this decades-long legal debacle. It affects the defendants in the case, including Altria, R.J. Reynolds Tobacco Company and four cigarette brands owned by ITG Brands LLC.

When reached for comment, a Reynolds Spokesperson said, “We firmly support raising public awareness of the harms of smoking cigarettes but these must respect the First Amendment protections that apply to all speakers, including manufacturers of tobacco products. We cannot comment further on pending litigation.”

Beginning on July 1, 2023, statements on the risks of smoking tobacco will be displayed on “eye-catching” signs at thousands of retail locations. As the DOJ noted in its announcement, roughly 200,000 retailers have merchandising agreements with the aforementioned tobacco companies allowing them to control how their cigarettes are displayed in-store.

The signs will include statements conveying the numerous diseases linked to tobacco, the estimated number of people who die from smoking as well as the addictive nature of cigarettes.

These signs are expected to stay up for two years, according to an agreement reached with tobacco retailers earlier in May.

“Cigarette companies misled the public for decades about the health risks of smoking and were ordered by a federal court to implement a series of corrective measures,” Brian Boynton, the principal deputy assistant attorney general, said in a statement.

“All of these measures have been implemented, except one—the display of corrective statements in retail stores that sell cigarettes. Today’s order requiring implementation of that remaining remedy is a major achievement that will educate American consumers and save lives,” Boynton added.

https://thehill.com/policy/healthcare/3765887-tobacco-companies-now-required-to-display-signs-at-retail-locations-stating-health-effects-of-smoking/

Biden administration to appeal ruling striking Title 42, pledges new regulation from CDC

 The Biden administration on Wednesday said it plans to appeal a court ruling striking down the Title 42 policy limiting asylum, forecasting that public health authorities plan to write a new regulation to replace it.

The coming appeal puts the Department of Homeland Security at the center of conflicting court cases on Title 42, which allows border officials to rapidly expel migrants without allowing them to seek asylum.

“CDC’s Title 42 Orders were lawful…[and] this Court erred in vacating those agency actions,” the government wrote in a filing before the District Court for the District of Columbia, which on Nov. 15 struck down Title 42.

In appealing the case, the Biden administration seeks to challenge a ruling that mooted a decision by another court in a case brought by the state of Louisiana, which had blocked the Centers for Disease Control and Prevention (CDC) from rescinding the policy with its April order.

Title 42, crafted in the early days of COVID-19 by the Trump administration, was marketed as a pandemic response policy, but most observers deemed it a transparent attempt to use the pandemic as an excuse to gut asylum.

The latest twist in the litigation continues the Biden administration’s complex relationship with the policy, which they have now used to expel far more migrants than under Trump.

“We are not surprised by the decision to appeal given the Biden administration’s vigorous legal defense of Title 42 over the past two years,” Lee Gelernt, a lawyer for the American Civil Liberties Union representing those suing over Title 42.

Wednesday’s filing also indicates the nation’s public health authorities are grappling with another policy that that could have implications at the border.

“HHS and CDC have themselves decided to undertake a new rulemaking to reconsider the framework under which the CDC Director may exercise her authority under [Title 42] to respond to dangers posed by future communicable diseases.”

The portion of the law references in the filing specifically deals with the “suspension of entries and imports.”

CDC did not immediately respond to request for comment seeking more details about the forthcoming rulemaking.

Any new policy limiting migration based on public health authorities under Title 42 could run counter to the CDC’s determination in April that the order limiting asylum was no longer necessary.

“Based on the public health landscape, the current status of the COVID-19 pandemic, and the procedures in place for the processing of covered noncitizens … CDC has determined that a suspension of the right to introduce such covered noncitizens is no longer necessary to protect U.S. citizens,” the CDC wrote at the time.

But the rule comes after DHS Secretary Alejandro Mayorkas hinted that DHS would explore other ways to limit migration for Venezuelans after the fall of Title 42. 

In its filing with the court, DHS said it would likewise seek a pause in litigation with Louisiana, where the government is arguing CDC properly rescinded Title 42 and its termination should be allowed to take effect.

DHS wrote the new regulations from CDC, “could likewise moot” the issues underpinning the Louisiana case.

In the ACLU case however, U.S. District Judge Emmet Sullivan last month found the rollout of Title 42 violated the Administrative Procedures Act (APA), writing the government “failed to adequately consider alternatives and the policy did not rationally serve its stated purpose.”

The judge also noted the CDC’s “decision to ignore the harm” caused by the policy likewise violated the APA.

“It is unreasonable for the CDC to assume that it can ignore the consequences of any actions it chooses to take in the pursuit of fulfilling its goals, particularly when those actions included the extraordinary decision to suspend the codified procedural and substantive rights of noncitizens seeking safe harbor,” Sullivan wrote, noting warnings that migrants often face persecution and violence once expelled.”

https://thehill.com/policy/national-security/3766086-biden-administration-to-appeal-ruling-striking-title-42-pledges-new-regulation-from-cdc/

Relmada again misses endpoint in Phase 3 depression trial

  Relmada Therapeutics, Inc. (Nasdaq: RLMD), a late-stage biotechnology company addressing diseases of the central nervous system (CNS), today announced results of the RELIANCE I study (REL-1017-301), evaluating REL-1017 as an adjunctive treatment for Major Depressive Disorder (MDD).  The same factors that negatively affected the previously announced results from the RELIANCE III study, a limited number of high enrolling sites with unplausible placebo response, also affected RELIANCE I and the study did not achieve its primary endpoint, which was a statistically significant improvement in depression symptoms compared to placebo as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) on Day 28.  RELIANCE I evaluated the use of REL-1017 in addition to a standard antidepressant for patients who had inadequate response to at least one and up to three standard antidepressant therapies.

https://finance.yahoo.com/news/relmada-therapeutics-announces-top-line-210500075.html

Spontaneous Cancer Regression 'Extremely Rare'

 Spontaneous regression of solid tumors in the absence of anticancer treatment has been known to occur, but it is extremely rare, a new study confirms.

After pooling placebo response rates from 45 cancer drug trials in advanced solid tumors, researchers found a complete response of 0% and a partial response of 1%.

"Now we can answer our patients," tweeted lead investigator Bishal Gyawali, MD, PhD, of Queen's University, Kingston, Canada. Without treatment, "the chance of complete response is almost zero and should not be relied upon! It's next to a miracle.

"Hopefully, this data will convince our patients to not abandon cancer therapy," Gyawali added.

The study was published online late last month in eClinicalMedicine.

Bhavana Pothuri, MD, who was not involved in the research, was not surprised by the "very low rate" of partial and complete responses among patients who receive placebos.

This study provides "important information as we speak to patients" in trials and shows them the "substantial benefit" cancer treatments can provide, Pothuri, gynecologic oncologist at NYU Langone Perlmutter Cancer Center, New York City, told Medscape Medical News.

Fred R. Hirsch MD, PhD, agreed that the results were "interesting but not entirely surprising." The main message of this study "is cancer needs to be treated," said Hirsch, of the Tisch Cancer Institute at Mount Sinai, New York City, who was not involved in the study.

However, a recent national survey by the American Society of Clinical Oncology (ASCO) found that 40% of Americans believed their cancer could be completely cured with alternative treatments alone. This belief may be fueled by anecdotal reports shared among people with cancer, Gyawali noted in his tweet.

Concerned that such anecdotes might dissuade some patients from seeking treatment, Gyawali and colleagues sought to better understand the frequency with which advanced solid tumors undergo spontaneous regression.

The team analyzed placebo response rates in 45 randomized controlled trials in which cancer drugs were used to treat advanced solid tumors. The authors note that the "best estimate for the chances of spontaneous regression can be inferred through the placebo response rates in randomized trials since placebo, by definition, are inert substances that do not have any anti-tumor effects of their own."

The trials, published between 2015 and 2021, involved a total of 5684 patients. The authors clarified that placebo consisted of a monotherapy or best supportive care and was not used in combination therapy, such as chemotherapy or immunotherapy plus placebo.

Of the 4760 patients evaluable for an objective response rate in the placebo arm, 94 (1.97%) achieved an objective response. A pooled analysis revealed an objective response rate of 1%.

Of 3808 patients who could be evaluated for partial or complete responses, only four (0.1%) achieved a complete response. The pooled complete response rate was 0%. In addition, just over 2% of patients who received placebo (83 of 3808) achieved a partial response, with a pooled partial response rate of 1% across trials.

Gyawali and colleagues found it "reassuring" that their pooled placebo response rates were in line with those in two other studies, which showed an objective response rate of 2% with placebo or no active treatment among patients with advanced solid tumors.

"Thus, we can safely communicate with our patients that the chances of response without treatment is probably 1%, and not more than 2% even in the most optimistic scenario," the authors write.

The authors note, however, that subgroup analyses based on tumor types revealed slightly higher objective response rates in the placebo arm for prostate cancer (7%) and sarcoma (4%).

The higher objective response rate in prostate cancer might be explained by the therapeutic effect of prednisone or by the ongoing use of androgen blockade outside of the study.

"However, a 4% response rate in sarcoma patients is intriguing, and lacks clear explanation," the team writes.

Potential limitations of the study include possible publication bias and heterogeneity of studies evaluated.

Despite these limitations, Gyawali and colleagues conclude that patients "should not expect complete regression of cancers without treatment."

The study had no funding. Gyawali receives consulting fees from Vivio Health unrelated to this study. Hirsch and Pothuri have disclosed no relevant financial relationships.

eClinMed. Published online November 24, 2022. Full text

https://www.medscape.com/viewarticle/985189

Cassava Completes Dosing in Open-label Study of Simufilam for Alzheimer’s

 

• Outside Biostatisticians with Specific Expertise in Alzheimer’s Disease Will Conduct an Independent Statistical Analysis on The Clinical Dataset.

• Clinical Dataset May Be Announced Approximately Year-End 2022, Pending Completion of Study Report by Outside Biostatisticians.

Cassava Sciences, Inc. (Nasdaq: SAVA), a clinical-stage biotechnology company, today announced the completion of drug administration in an open-label study of simufilam for Alzheimer’s disease. This study was designed to evaluate long-term drug safety and to measure cognitive changes (ADAS-cog) over 12 months in approximately 200 patients with mild-to-moderate Alzheimer’s disease treated with open-label simufilam 100 mg twice daily. Simufilam is Cassava Sciences’ oral drug candidate for Alzheimer’s disease dementia.

To ensure the highest integrity of data analysis, outside biostatisticians with specific expertise in Alzheimer’s disease will conduct an independent statistical analysis on the clinical dataset. Cassava Sciences may announce study results approximately year-end 2022, pending completion of a study report by outside biostatisticians.

https://finance.yahoo.com/news/cassava-sciences-announces-completion-dosing-141500200.html

CBD Oil No Help in Relieving Disease-Related Symptoms in Advanced Cancer

 Cannabidiol (CBD) oil failed to improve cancer-related symptoms beyond the benefits of palliative care, a randomized phase II trial showed.

The change in a standard symptom scale was actually greater with the addition of placebo to palliative care: -6.2 points versus -3.0 points with CBD oil. The proportion of patients who met criteria for response also favored the placebo group, and the change in scores for individual symptoms did not differ between the placebo and CBD oil groups, Janet Hardy, MD, of the University of Queensland in Brisbane, Australia, and colleagues reported in the Journal of Clinical Oncology.

"This study has significant implications for policymakers regarding both approved indications for MC [medical cannabis] and its safe use," the authors wrote. "Medical cannabis has been approved in several countries for palliative care in the belief that it might improve the QoL [quality of life] of patients with advanced disease.

"CBD is a popular cannabis product in the community as it has no psychoactive effects and does not impair driving ability," the team added. "With current evidence, it is difficult to justify government subsidization of the cost of CBD nor recommend that patients pay for CBD products."

The results are not surprising, said Marcin Chwistek, MD, a supportive care and palliative medicine specialist at Fox Chase Cancer Center in Philadelphia, who was not involved with the study.

"The results are consistent with what I have observed in our clinical practice," he told MedPage Today via email. "CBD oil alone is widely available and used by many cancer patients. However, very few patients seem to benefit from it. It is important to note that patients were also receiving standard palliative care that focuses on the management of cancer-related symptoms and already utilizes many effective therapies. Therefore, it may be difficult to observe a meaningful change in patients' symptoms with a short term addition of CBD oil."

Using a different cannabis product might have made a difference, such as a 1:1 combination of THC and CBD, Chwistek continued. Limited evidence suggests that combination is helpful for cancer-related pain.

The oncology community has mixed feelings about use of medicinal CBD. Despite a lack of evidence, the products are usually well tolerated, so many oncologists do not discourage the products' use, particularly when patients express an interest.

"What is also needed is evidence related to the potential effect of MC [medical cannabis] on the growth of cancer cells or effects of anticancer therapy," said Chwistek. "At this time, we do not know if MC interferes with anticancer therapy in any meaningful way."

The trial did provide some needed evidence regarding use of CBD products in patients with advanced cancer, said Kimberson Tanco, MD, of the University of Texas MD Anderson Cancer Center in Houston. Most published systematic reviews have shown limited supporting evidence. Controlled clinical trials with more patients followed for longer duration are needed to assess CBD products' benefits and toxicities, but such studies have been challenging to conduct.

"Personally, as an actively practicing clinician, the majority of reports of symptom-related benefits that I have heard have also been anecdotal from patients' or caregivers' accounts," said Tanco.

He also has sensed mixed feelings among oncology practitioners toward use of CBD to manage cancer symptoms.

"Clinicians are asked more and more by patients and their caregivers regarding the potential role and use of these products while reporting limited knowledge of these products," said Tanco.

The Australian study involved 144 patients with advanced cancer and symptom distress, as reflected by an Edmonton Symptom Assessment Scale (ESAS) total score ≥10/90. All patients received standard professionally administered supportive/palliative care and were randomly assigned to CBD oil or placebo for 28 days. The primary outcome was change in ESAS total score at day 14, and response was defined as a decrease in ESAS total score ≥6 on day 14.

The results showed no statistically significant difference in ESAS total score at day 14, although the numerical comparison favored the placebo group. In the placebo group, 58.7% of patients met criteria for response as compared with 44.8% in the CBD oil group, which was also not significantly different. Individual components of the ESAS declined in both groups with no significant differences between groups. The titrated dose of CBD oil did not have any significant associations with opioid dose.

"There was no detectable effect of CBD on quality of life, depression, or anxiety," the authors said of the results. "Adverse events did not differ significantly between arms apart from dyspnea that was more common with CBD. Most participants [in both groups] reported feeling better or much better at days 14 ... and 28."

Disclosures

The study was supported by the Commonwealth of Australia Medical Research Future Fund.

Hardy disclosed a relationship with GD Pharma.

Chwistek and Tanco reported no relevant relationships.

Primary Source

Journal of Clinical Oncology

Source Reference: Hardy J, et al "Phase IIb randomized, placebo-controlled, dose-escalating, double-blind study of cannabidiol oil for the relief of symptoms in advanced cancer (MedCan1-CBD)" J Clin Oncol 2022; DOI: 10.1200/JCO.22.01632.

https://www.medpagetoday.com/hematologyoncology/othercancers/102108

Xeljanz Cancer Risks Detailed

 The degree to which the oral rheumatology drug tofacitinib (Xeljanz) seems to promote new malignancies is now fleshed out in the latest, and at least somewhat reassuring, report from a landmark safety study.

Tofacitinib at either 5 or 10 mg twice daily in the so-called ORAL Surveillance trial was associated with incident cancers at a rate of 1.13 per 100 patient-years of treatment, compared with 0.77 per 100 patient-years with tumor necrosis factor (TNF) inhibitors, according to Jeffrey Curtis, MD, of the University of Alabama at Birmingham, and colleagues.

That worked out to a hazard ratio of 1.48 (95% CI 1.04-2.09) for tofacitinib versus TNF inhibitor therapy, the group reported in Annals of the Rheumatic Diseases.

Some of the data had been reported earlier -- in a press release from tofacitinib maker Pfizer and in a New England Journal of Medicine paper this past January -- but the new publication includes substantially more detail, including 50 pages of supplementary tables and figures on top of the 13-page main paper.

ORAL Surveillance began in 2014 under orders from the FDA, following the drug's initial approval for rheumatoid arthritis in 2012. (It has since gained approvals for psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and ulcerative colitis.) The registration trials showed signs that tofacitinib increased risks of certain malignancies, as well as infections, and its first label included boxed warnings about them. However, the agency wanted Pfizer to produce a clearer picture of the risks with a dedicated safety study. After ORAL Surveillance data first became available in 2021, the warnings were beefed up.

The new report now provides additional details on the malignancy risk, including rates of specific cancer types and numbers needed to harm as compared with TNF inhibitors.

Curtis and colleagues randomized 4,362 patients at a 1:1:1 ratio to tofacitinib at 10 or 5 mg twice daily or to one of two TNF inhibitors. Patients were enrolled at 323 sites in 30 nations. In North America, the assigned TNF inhibitor was adalimumab (Humira); etanercept (Enbrel) was used elsewhere. After an interim analysis in 2019 showed increased mortality for the higher tofacitinib dose, that arm was terminated and its patients were shifted to the lower dosage. Adalimumab and etanercept doses were the customary standards, and all patients continued on methotrexate.

Only individuals 50 and older with rheumatoid arthritis not responding to methotrexate were enrolled (approvals for the other previously mentioned indications all came after the trial was designed). Patients were also required to have at least one cardiovascular risk factor beyond age.

In total, 122 malignancies (not counting non-melanoma skin cancers) developed in the two tofacitinib groups -- 62 with the lower dose and 60 with the higher dose -- versus 42 in the TNF inhibitor arm.

Lymphomas were among the first cancer types to draw scrutiny, and the new data back that up: Curtis and colleagues calculated a hazard ratio of 5.09 for the two tofacitinib doses combined relative to TNF inhibitors. However, the 95% confidence interval was extremely broad and spanned 1.0 (0.65-39.78, to be precise) because there were only 10 cases total with tofacitinib and just one in the TNF inhibitor group. Lung cancer also appeared to be substantially more common with tofacitinib (HR 2.17, 95% CI 0.95-4.93), as did cutaneous squamous cell tumors (HR 2.32, 95% CI 1.08-4.99) and non-melanoma skin cancers overall (HR 2.02, 95% CI 1.17-3.50).

For cancers overall, the researchers found a number needed to harm of 55 with 5 years of tofacitinib treatment -- that is, treating 55 patients for 5 years would lead to one extra cancer case relative to what would be expected with TNF inhibitors.

Kaplan-Meier curves showed that tofacitinib's extra cancer risk became clearest after about 3 years of treatment. At year 5, some 97% of the TNF inhibitor group remained cancer-free, versus 94% of the tofacitinib groups combined. There was no obvious dose-relationship for tofacitinib and cancer rates.

Also noteworthy were findings that the following were associated with increased cancer risk, based on all three treatment arms combined:

• White race versus non-white race
• North American residence
• Current or past smoking versus never-smokers
• Higher versus lower cardiovascular risk score
• History of cardiovascular disease versus no history
• Increasing age

These factors generally applied to lung cancers and non-melanoma skin cancers, as well as to all malignancies excluding non-melanoma skin cancers. Curtis and colleagues cautioned that some of these findings were interrelated (e.g., participants in North America came into the study with generally higher cardiovascular risk scores) or could have been influenced by use of medications such as non-steroidal anti-inflammatory drugs, which may carry cancer risks of their own.

Limitations cited by the authors included that the trial was not designed to assess differential risks for specific cancer types, and that cardiovascular risk scores included a fixed 1.5-fold increase in the statistical analysis to account for the presence of rheumatoid arthritis, which Curtis and colleagues called "a crude approximation."

Disclosures

The trial was sponsored by Pfizer and required by the FDA.

Study authors reported extensive relationships with pharmaceutical companies including Pfizer and other commercial entities.

Primary Source

Annals of the Rheumatic Diseases

Source Reference: Curtis JR, et al "Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial" Ann Rheum Dis 2022; DOI: 10.1136/ard-2022-222543.

https://www.medpagetoday.com/rheumatology/generalrheumatology/102106