ADC Therapeutics readies IPO

ADC Therapeutics SA (ADCT) has filed a prospectus for a $150M IPO.

The Swiss biotech develops antibody-drug conjugates (ADCs) to treat cancer that use pyrrobenzodiazepines (PBDs), a class of natural products produced by actinomycetes bacteria, as the cytotoxic agent. The company says PBD toxins are 100 times more potent than the cytotoxic agents (called warheads) used in ADCs currently on the market.

Lead candidates are ADCT-402 (loncastuximab tesirine), in Phase 2 development for relapsed/refractory diffuse large B-cell lymphoma (preliminary 41.7% response rate) and non-Hodgkin lymphoma (41.4% response rate in a Phase 1 study), and ADCT-301 (camidanlumab tesirine), in Phase 2 development for relapsed/refractory Hodgkin lymphoma (86.5% response rate in Phase 1).

If current studies are successful, the company expects to file a U.S. marketing application for ADCT-402 in H2 2020 followed by ADCT-301 in H1 2022.

2019 Financials (6 mo.): Contract Revenue: $2.3M (+274%); Net loss: ($49.9M) (+19%); Cash Consumption: ($55.7M) (+9%).

Related ticker: Seattle Genetics (NASDAQ:SGEN)

https://seekingalpha.com/news/3497803-adc-therapeutics-readies-ipo

CMS gets new powers to go after Medicare, Medicaid fraudsters

The Trump administration issued a new rule that aims to prevent payments to Medicare and Medicaid fraudsters by boosting revocation powers and extending the time before troublesome organizations can rejoin the programs.

The Centers for Medicare & Medicaid Services said that the final rule issued Thursday marks a major turnaround from the agency’s normal approach of attempting to recoup fraudulent payments after the fact.

“For too many years, we have played an expensive and inefficient game of ‘whack-a-mole’ with criminals⁠—going after them one at a time⁠—as they steal from our programs,” CMS Administrator Seema Verma said in a statement Thursday. “Now for the first time, we have tools to stop criminals before they can steal from taxpayers.

The rule gives CMS new powers to revoke or deny organizations from participating in Medicare, Medicaid or the Children’s Health Insurance Program.

A new “affiliations” authority lets CMS identify individuals or organizations that have a high risk of fraud, waste or abuse based on their association with previously sanctioned people or groups, a release on the new rule said.

“For example, a currently enrolled or newly enrolling organization that has an owner/managing employee who is ‘affiliated’ with another previously revoked organization can be denied enrollment in Medicare, Medicaid, and CHIP or, if already enrolled, can have its enrollment revoked because of the problematic affiliation,” the agency said.

Over the last five years, nearly $52 billion has been paid to 2,097 entities that were affiliated with an individual or company that had their enrollment revoked, the final rule said. CMS estimates it could save $20.7 billion over five years through the new affiliation authority.

The definition of an affiliation includes if a supplier or provider has a 5% or greater direct or indirect ownership stake in a revoked organization, has a general or limited partnership or if an individual has operational or managerial control over day-to-day operations of the organization, according to the rule.

CMS also now has the authority to revoke or deny Medicare enrollment if a revoked provider or supplier tries to come back in under a different name. CMS can also revoke or deny enrollment if a provider or supplier bills for services or items from a non-compliant location or if they have an outstanding debt from the Treasury Department for an overpayment.

The rule also enables CMS to prevent an application from enrolling in one of the programs for up to three years if a provider or supplier submitted false or misleading information in their enrollment application.

Under the new regulations, a revoked provider could re-enroll in Medicare, Medicaid or CHIP after 10 years. This is a major increase from the previous penalty of waiting only three years. If a provider or supplier gets revoked for a second time, then it must wait two decades before it can rejoin the program.

The new authorities go into effect on Nov. 4.

Federal health programs such as Medicare and Medicaid are a plum target for fraudsters due in part to the large number of payments the federal government doles out. The Government Accountability Office has said that improper Medicaid payments, for instance, reached $37 billion in 2017.

CMS said that it has been working to combat fraud and waste. The agency cited the improper payment rate for Medicare’s fee-for-service program was 8.12%, the lowest since 2010.

https://www.fiercehealthcare.com/payer/cms-gets-new-powers-to-go-after-medicare-medicaid-fraudsters

Greater Cognitive Decline Seen in Seniors Unaware of Having Hypertension

For adults aged 55 years and older, those unaware they have hypertension have greater cognitive decline, according to a study presented at the American Heart Association Hypertension 2019 Scientific Sessions, held from Sept. 5 to 8 in New Orleans.

Shumin Rui, from Columbia University in New York City, and colleagues followed a national sample of 10,958 mid-aged and elderly Chinese for four years. The correlation of hypertension status and treatment with cognitive decline over time was assessed in different age groups.

The researchers observed a decrease in overall cognition scores, from 11.01 in 2011 to 10.24 in 2015. For 6,971 participants aged 55 years and older, there was a 0.57-point larger cognition decline for patients with hypertension who were not aware of their condition compared with those without hypertension; compared with those who were unaware of their hypertension, those on antihypertensive treatment had a 0.56-point smaller cognition decline. Cognition decline was similar for patients on antihypertensive treatment and those without hypertension. After adjustment for education, gender, and residency, the results were similar. No differences in cognition decline were seen for any group of participants aged 45 to 54 years.

“We think efforts should be made to expand high blood pressure screenings, especially for at-risk populations, because so many people are not aware that they have high blood pressure that should be treated,” Rui said in a statement.

https://www.physiciansbriefing.com/cardiology-2/high-blood-pressure-health-news-358/greater-cognitive-decline-seen-in-seniors-unaware-of-having-htn-749861.html

Diabetes Control Has Stalled Across U.S.

U.S. adults with diabetes are no more likely to meet disease control targets than they were in 2005, a new study finds.

Typically, diabetes treatment focuses on controlling blood sugar, blood pressure and cholesterol levels, as well as not smoking.

For the study, Massachusetts General Hospital researchers analyzed data on diabetes care in the United States from 2005 through 2016. The investigators found that one in four adults with diabetes was not diagnosed, and nearly one in three was not receiving appropriate care for diabetes.

“Fewer than one in four American adults with diagnosed diabetes achieve a controlled level of blood sugar, blood pressure and cholesterol and do not smoke tobacco,” said study lead author Pooyan Kazemian, of the hospital’s Medical Practice Evaluation Center.

“Our results suggest that, despite major advances in diabetes drug discovery and movement to develop innovative care delivery models over the past two decades, achievement of diabetes care targets has not improved in the United States since 2005,” Kazemian said in a hospital news release.

More than 30 million Americans have diabetes. Most have type 2, which is linked to lifestyle.

Certain groups of patients were less likely to achieve diabetes care targets, according to the study.

“Younger age (18-44), female and nonwhite adults with diabetes had lower odds of achieving the composite blood sugar, blood pressure, cholesterol and nonsmoking target,” Kazemian said.

Patients with insurance coverage were most likely to have been diagnosed with diabetes and to have achieved treatment targets, the researchers noted.

According to study senior author Dr. Deborah Wexler, “Barriers accessing health care, including lack of health insurance and high drug costs, remain major factors that have not been adequately addressed on a population level.” Wexler is with the hospital’s diabetes unit and is an instructor in medicine at Harvard Medical School.

“Treatment advances in diabetes mellitus can meaningfully improve outcomes only if they effectively reach the populations at risk. Our findings suggest this is not the case in the U.S.,” Wexler said.

The findings, she added, indicate an immediate need for better approaches to diabetes care delivery, “including a continued focus on reaching underserved populations with persistent disparities in care.”

The study was published online recently in JAMA Internal Medicine.

https://consumer.healthday.com/diabetes-information-10/misc-diabetes-news-181/diabetes-control-has-stalled-across-u-s-749225.html

Tiny fat bubbles key to rebooting immune system, calming disease process

People living with inflammatory autoimmune disease could benefit from an ‘immune system reboot’, and researchers have isolated specific cells to target.

The University of Queensland’s Professor Ranjeny Thomas said the research findings give hope for similar new immunotherapies for people with diseases like rheumatoid arthritis and vasculitis.

People with these diseases currently require daily medications to modify or suppress their immune system.

Rheumatoid arthritis and vasculitis have a huge impact on those living with them because there is no cure, and medication generally cannot be stopped.

We think a better strategy would be to restore and re-regulate the specific part of the immune response that has gone wrong.”

Professor Ranjeny Thomas, University of Queensland

She said such “precision medicines” were a big focus for researchers seeking new ways to treat and prevent autoimmune diseases.

Her research team has reported an “antigen-specific immunotherapy”, and demonstrate that it could re-regulate the rogue immune T-cells that are markers of inflammatory arthritis or vasculitis in mice.

“We found that dendritic cells – conductors of the immune system orchestra – absorb tiny fat bubbles we generated, restoring immune regulation,” Professor Thomas said.

“These fat bubbles, called liposomes, held the key to rebooting the immune system and calming the disease process.

“This study shows in mice that antigen-specific immunotherapy can be used to treat existing inflammatory autoimmune diseases, as well as to prevent future disease.

“Importantly, it shows that inflammatory activity is not a barrier to restoring regulation in the immune system.”

People living with rheumatoid arthritis or vasculitis have rogue T-cells that attack the body’s own tissues, escaping the normal regulation that keeps these cells in check.

The antigen-specific liposome immunotherapy treatment helps restore immune cells to healthy function.

The research brings doctors closer to understanding the best ways to use precision medicine for human inflammatory autoimmune diseases.

Source:

University of Queensland

Journal reference:

Galea, R. et al. (2019) PD-L1 and calcitriol dependent liposomal antigen-specific regulation of systemic inflammatory autoimmune disease. JCI Insight. doi.org/10.1172/jci.insight.126025.

https://www.news-medical.net/news/20190907/Tiny-fat-bubbles-hold-key-to-rebooting-the-immune-system-and-calming-disease-process.aspx

Focus on Biden health underscores Trump attacks

Conservative media’s focus on Joe Biden’s health this week underscores how attacks on the former vice president’s age are likely to be a big part of the race if he’s the Democratic nominee.

Biden will turn 77 this fall, and the issue of his age has repeatedly resurfaced since he entered the presidential race.

President Trump, who is just four years younger than Biden, already has made a number of allusions to Biden’s age, accusing the former vice president just last month of “not playing with a full deck.”

Democrats and Republicans alike say they expect Trump to continue to play the age card, particularly whenever Biden makes a gaffe.

“They’re going to make it all about him not being physically fit for the job,” said Shermichael Singleton, a Republican strategist who briefly worked for the Trump administration. “Republicans will use it to point out that he’s not ready for the job on day one.”

The Drudge Report this week made a banner headline out of a story from the conservative Washington Examiner about a broken blood vessel in Biden’s left eye.

Mainstream media outlets barely mentioned the incident, and the blood in Biden’s eye was hardly noticeable for many people watching the climate summit hosted live by CNN.

But right-wing outlets played Biden’s eye as a major piece of news, foreshadowing attacks likely to come next summer and fall if Biden, the Democratic front-runner, wins his party’s nomination.

The effort would be familiar to anyone who remembered attacks on Hillary Clinton’s age and physical stamina in 2016.

Singleton predicted that Republicans will use “the same tactics” they used against Clinton in 2016 after she had pneumonia and nearly fainted at a Sept. 11 event that year.

Democrats — particularly those who worked for Clinton — agree with that sentiment.

Zac Petkanas, a Democratic strategist who worked on Clinton’s 2016 campaign, said it’s part of a larger narrative driven by conservatives.

“All candidates should be on the lookout,” Petkanas said, adding that it “certainly did have an impact” on Clinton’s campaign and could also dent candidates such as Biden.

He also suggested the argument could also be used against any Democrat who could be classified as a senior citizen. The two Democrats chasing Biden in polls are Sen. Elizabeth Warren (D-Mass.), who is 70, and Sen. Bernie Sanders (I-Vt.), who is 77.

“Anybody over 60 would be susceptible,” Petkanas said.

Adam Parkhomenko, who also worked on Clinton’s 2016 campaign, added that it’s “part of a limited line of attacks” that Republicans have “always used and are clearly planning to use this time.”

Other Democrats haven’t made an issue of Biden’s age, though some strategists say it will be fair game this fall as the race gets hotter — particularly if Biden makes more verbal flubs.

Implicit, age-based attacks already are appearing.

Tech businessman Andrew Yang, for example, said this week that electing Biden would take the country back in time — a nod to the attack by some Democrats that Biden is not from the generation that should lead the party in the future.

It wasn’t an attack on Biden’s health or even a direct attack on his age, but it skirted close to the issue.

Rep. Tim Ryan (D-Ohio), one of the lower-tier Democratic challengers, also said he didn’t think Biden had what it takes to defeat Trump.

“I just think Biden is declining. I don’t think he has the energy,” Ryan said, according to Bloomberg News. “You see it almost daily. And I love the guy.”

Ryan later added he did not know he was speaking to a reporter and that he was trying to raise money for his campaign, Bloomberg reported.

“The Democratic presidential campaign is as much a generational battle as it is an ideological contest,” said Democratic strategist Brad Bannon, adding that the Democratic victories in 2018 of young progressive candidates such as Reps. Alexandria Ocasio-Cortez (D-N.Y.) and Ayanna Pressley (D-Mass.) against older Democrats “were manifestations of generational conflict.”

Biden’s campaign declined to comment for this story.

Sanders and Warren may not want to make age an issue, but former Rep. Beto O’Rourke (D-Texas) and South Bend, Ind., Mayor Pete Buttigieg may try “to capitalize,” Bannon said.

“So any physical problem like Biden’s eye that raises questions about a 70-something candidate’s health will be an ongoing storyline for the media and a problem for his campaign,” he added.

Biden allies say they expect Trump to continue to come after the candidate as the primary plays out and the former vice president looks to retain his front-runner status.
https://thehill.com/homenews/campaign/460319-focus-on-biden-health-underscores-future-trump-attacks

Prescription Databases May Miss Opioid-Benzo Combinations

Prescription data alone underestimated how many patients combined opioids and benzodiazepines, an analysis of Quest Diagnostics drug test data indicated.

Among a selected sample of patients whose drug test indicated concurrent benzodiazepine and opioid use, 64% had at least one benzodiazepine or opioid that was not prescribed, according to Quest researcher Leland McClure, PhD, and colleagues in a poster presentation at the 2018 PAINWeek conference.

“Clinicians need to be aware if their patients are using potentially dangerous combinations of drugs like benzodiazepines and opioids,” McClure told MedPage Today. “Because state-based prescription drug monitoring programs are limited to drugs prescribed, more effective detection of drug use is achieved by supplementing the prescribed drug database information with objective methods like drug testing.”

Benzodiazepines can increase the respiratory depressant effects of opioids: a recent review of health claims data showed that among opioid users, concurrent use of benzodiazepines more than doubled the risk of an overdose-related emergency room or inpatient visit. An estimated 23% of people who died of an opioid overdose in 2015 also tested positive for benzodiazepines. Both prescription opioids and benzodiazepines now carry FDA boxed warnings highlighting the dangers of using these drugs together.

The Quest Diagnostics analysis was based on 456,675 sets of test results from 276,953 patients in 50 states and the District of Columbia in 2017. Specimens were from patients who were prescribed at least one drug and who were tested for both opioids and benzodiazepines. All results included a report indicating what tested medication was prescribed and whether the prescribed drugs were detected in a specimen.

The laboratories performed drug testing with quantitative definitive tandem mass spectrometry; presumptive immunoassay screens preceded some of these tests. Immunoassays were performed using tests modified to detect target drugs exhibiting low cross-reactivity. “Our analysis defined relationship groups to ensure that drugs that could be metabolites of other drugs did not falsely inflate positivity rates,” McClure added.

In this cohort, 68.2% of specimens tested positive for opioids (including buprenorphine and methadone) and 29.2% tested positive for benzodiazepines. Overall, 20.6% of specimens tested positive for concurrent use of benzodiazepines and opioids. Of these patients, 36% had been prescribed both drug classes and 64% had at least one non-prescribed drug.

About 16% of specimens that tested positive for prescribed opioids also tested positive for non-prescribed benzodiazepines. Similarly, about 13% of specimens that tested positive for prescribed benzodiazepines tested positive for non-prescribed opioids.

“The extent of concurrent use of benzodiazepines and opioids, particularly non-prescribed use, cannot be determined by prescription drug database monitoring programs alone,” the researchers concluded.

The CDC recommends reviewing prescription drug monitoring program data to determine whether a patient is receiving combinations like opioids and benzodiazepines that may create a high risk for overdose, performing urine drug tests before starting patients on opioid therapy, and considering drug testing at least annually to assess for prescribed medications and illicit drugs.

The analysis has several limitations: With 68% of specimens testing positive for opioids, the results may be more representative of a monitored group of patients than the general population; also, complete prescribing information may not have been available.

This analysis was funded by Quest Diagnostics.

The authors are employees of Quest or consultants for the company; they reported having no other conflicts of interest.

Primary Source
PAINWeek
Source Reference: Gudin J, et al “Concurrent use of opioid and benzodiazepine:what the prescription drug monitoring database does not tell you” PAINWeek 2018; Abstract 44.

https://www.medpagetoday.com/meetingcoverage/painweek/75006