Medicare going in ‘right direction’ on opioid epidemic

Prescriptions for two drugs used to treat opioid addiction increased significantly from 2016 to 2018 for people on Medicare, according to a federal report out Wednesday.

About 174,000 Medicare beneficiaries received such a medication—either buprenorphine or naltrexone—to help them with recovery in 2018, according to the Office of Inspector General (OIG) in the Department of Health and Human Services.

In addition, prescriptions for naloxone, the drug that can reverse an opioid overdose, spiked since 2016, rising 501%―and that is likely an underestimate because it doesn’t include doses of the nasal spray Medicare members might have received through local programs, the OIG said.

“For now, the numbers are going in the right direction,” said Miriam Anderson, lead investigator on the report. “But this is a national crisis and we must remain vigilant and continue to fight this epidemic and ensure that opioids are prescribed and used appropriately.”

During the two years studied, the threat of new addictions appeared to slow. Prescriptions for an opioid through Medicare Part D decreased by 11%. The numbers of the beneficiaries considered at serious risk for misuse or overdose―either because they received extreme amounts of opioids or appeared to be “doctor shopping”―dropped 46%. And there were 51% fewer doctors or other providers flagged for prescribing opioids to patients at serious risk from 2016 through 2018.

The report says the OIG and other law enforcement agencies will investigate the highest-level prescribers for possible fraud and signs that some providers operate pill mills. The report mentions a physician in Florida who provided 104 high-risk Medicare patients with 2,619 opioid prescriptions.

It will be up to Medicare to follow up with patients whose opioid use suggests addiction, recreational use or resale. In one case, a Pennsylvania woman received 10,728 oxycodone pills and 570 fentanyl patches from a single physician during 2018. A Medicare member in Alabama acquired 56 opioid prescriptions from 25 different prescribers within one year.

In a statement, the Centers for Medicare & Medicaid Services (CMS) said: “Fighting the opioid epidemic has been a top priority for the Trump administration. We are encouraged by the OIG’s conclusion which finds significant progress has been made in our efforts to decrease opioid misuse while simultaneously increasing medication-assisted treatment in the Medicare Part D program.”

The agency points to recent efforts to curb opioid misuse including a 7-day limit on first-time opioid prescriptions, pharmacy alerts about Medicare beneficiaries who receive high doses of pain meds and drug management programs that may restrict a patient’s supply. CMS says it does not use a “one-size-fits-all” approach. Medicare patients in long-term care facilities or hospice care and those in cancer treatment are exempt from the opioid-prescribing restrictions.

The opioid-prescribing limits are raising alarms among some Medicare recipients, especially those who qualify based on a long-term disability and deal with severe, chronic pain.

Jae Kennedy, a disability policy expert at Washington State University, said cutting back on opioid prescriptions is generally a good development.

“But we hear from people in the disability community who feel like they’re being victimized by this new, very stringent set of dispensing limits,” said Kennedy. “People have been managing their pain, in some cases for many years without a problem, and now they’re being kind of criminalized by this new bureaucratic backlash.”

Anderson said the OIG agrees that “some patients need opioids and they should receive those needed for their condition. This report raises concerns that some patients may be receiving opioids above and beyond those needs.”

While most Medicare beneficiaries are 65 or older, the 15% who are under 65 and disabled may be the key piece of this report. Kennedy’s research shows they are up to three times more likely to describe persistent pain than are other adults and 50% more likely to report opioid misuse. A 2017 OIG report found that 74% of Medicare beneficiaries at serious risk for addiction and overdose deaths were under age 65.

Kennedy said it’s good to see Medicare expanding access to medication-assisted treatment, known as MAT, for addiction, but the agency needs to make sure that more buprenorphine prescribers accept all patients, not just the ones who are easiest to manage. Patients with disabilities often need many different medications for multiple physical and mental health conditions.

“Saying, ‘Well, because you’ve got schizophrenia or manic depressive disorder, we can’t treat you,’ I think is discriminatory,” Kennedy said. “It’s happening with private buprenorphine prescribers in this country because there are so few.”

Americans 65 or older have the lowest rates of opioid overdose deaths. Even so, the CDC says the number of deaths among seniors increased by 279% from 1999 to 2017.

https://www.fiercehealthcare.com/practices/medicare-going-right-direction-opioid-epidemic

Azar: Drug rebates’ ‘days are numbered’ despite rule setback

Though the Trump administration has withdrawn its plan to eliminate legal protections for drug rebates in Medicare Part D, Health and Human Services (HHS) Secretary Alex Azar said Thursday that the White House has not changed its stance on the practice.

What ultimately killed the rule was the growing body of evidence—including analysis from the Congressional Budget Office—suggesting that it would lead to higher Part D premiums for seniors, a risk that made President Donald Trump and other officials skittish, the HHS chief told reporters. “Rebates’ days are numbered,” Azar said, “but we’re not going to take any action that could run the risk of seniors’ premiums going up.”

The act of even introducing the rule as proposal created ripple effects in the industry, Azar said, as evidenced by a number of commercial insurers moving toward pass-through or direct-to-consumer discounts.

UnitedHealthcare and CVS Health headline the list of insurers that are aiming to move away from the drug rebate structure and toward discounts offered to members at the pharmacy counter.

In addition, Azar said that Congress could still take action on drug rebates, and that legislators would have more tools at their disposal to potentially avoid adverse effects like higher premiums.

Azar said that administration officials were well aware in January when they proposed the rule that it could impact premiums. As such, he said he “totally supports” the president’s decision to pull the plug on the plan.

“That was a known risk in our proposal—that is why we put this rule out for public comment,” he said.

Industry groups representing pharmacy benefit managers and insurers cheered the rule’s demise on Wednesday, though the Pharmaceutical Research and Manufacturers of America, the pharma industry trade group, called it a “blow” to seniors.

“Of all the policies proposed in Washington right now, this was the only proposal that would provide immediate savings at the pharmacy counter, instead of only saving the government or insurance companies money,” PhRMA said in a statement.

The decision to toss the rebate rule is the second major setback this week for the administration on its ambitious plans to address drug pricing. On Monday evening, a federal judge blocked an HHS rule that would force pharmaceutical companies to list their prices in television ads.

Despite that ruling, Azar said the administration still supports state initiatives and congressional efforts to put prices in ads. Drug companies “ought to be ashamed” of their pricing, which is why they’re opposing greater transparency so strenuously, he said.

“I have been very clear from the outset, as has the president, that there’s not a silver bullet to deal with the problem of drug pricing,” Azar said.

https://www.fiercehealthcare.com/payer/azar-drug-rebates-days-are-numbered-despite-rule-setback

Boosting CAR-T to treat solid tumors with a vaccine

Therapeutic cancer vaccines are designed to direct a person’s own immune cells against tumors. What if we could use that approach to prime CAR-T cells so that these engineered T cells—which are currently only able to tackle blood cancers—could work against solid tumors? Massachusetts Institute of Technology researchers did just that in mice.

Using a vaccine that super-charges CAR-Ts at the lymph nodes, an MIT team found that they could eliminate solid tumors in 60% of mice. After that, the animals also cleared re-injected tumor cells. The findings were published in Science.

CAR-T cell therapies use a patient’s own T Cells and a chimeric antigen receptor (CAR) to target cancer cells. Scientists believe one reason CAR-Ts don’t work well for solid tumors is that those cancers form a hostile environment around them that suppresses the T cells. The MIT team overcame this obstacle by stimulating CAR-T cells at the lymph nodes, the major sites of immune cells.

“Our hypothesis was that if you boosted those T cells through their CAR receptor in the lymph node, they would receive the right set of priming cues to make them more functional so they’d be resistant to shutdown and would still function when they got into the tumor,” Darrell Irvine, the study’s senior author, said in a statement.

Irvine’s team previously developed a method that delivers vaccines made of viral or bacterial antigens directly to lymph nodes, thereby provoking a stronger immune response. The vaccine is linked to a lipid tail that binds to albumin, a protein found in the bloodstream. Because albumin accumulates in lymph nodes, it allows the vaccine to hitchhike to the immune organ.

To build the new vaccine, the team used an antigen that stimulates the CAR-T cells. The antigen could be either the same tumor antigen to be targeted by the T cells, or a random molecule that the researchers selected.

The vaccines dramatically boosted CAR-T cell populations in mice, the researchers found. Mice given about 50,000 CAR-T cells sans vaccine showed nearly no CAR-T cells in the bloodstream. But CAR-T cells comprised up to 65% of the animals’ total T cell population in animals that got the vaccine.

The two-pronged eliminated such tumors as glioblastoma, breast and melanoma in 60% of mice, while solo CAR-T treatments produced no effect on those tumors, the team reported.

The animals that achieved tumor clearance were then re-challenged with tumor cells. Tumor cells that were identical to the original ones disappeared. Next, the researchers injected slightly different tumor cells, which did not express the antigen originally targeted by the CAR-T cells, and those tumor cells were eliminated, as well.

“That is another exciting aspect of this strategy,” Irvine said. “You need to have T cells attacking many different antigens to succeed, because if you have a CAR-T cell that sees only one antigen, then the tumor only has to mutate that one antigen to escape immune attack. If the therapy induces new T-cell priming, this kind of escape mechanism becomes much more difficult.”

Enthusiasm is swirling around the idea of using powerful CAR-T cells to treat solid tumors. Scientists at La Jolla Institute for Immunology found that removing a family of proteins called Nr4a transcription factors could rejuvenate CAR-T cells that have grown exhausted in the tumor microenvironment. Another team of scientists from MIT and Boston Children’s Hospital recently sought inspiration from alpacas and built CAR-T cells that can recognize certain proteins that protect tumors.

The MIT team’s technology has been licensed to Elicio Therapeutics, which raised $30 million to help fund its first human studies in the first half of 2020. “There’s really no barrier to doing this in patients pretty soon, because if we take a CAR-T cell and make an arbitrary peptide ligand for it, then we don’t have to change the CAR-T cells,” Irvine said in the statement. “I’m hopeful that one way or another this can get tested in patients in the next one to two years.”

https://www.fiercebiotech.com/research/boosting-car-t-to-treat-solid-tumor-a-vaccine

CRISPR pioneer Zhang targets brain diseases with new RNA-editing system

Feng Zhang, a gene-editing pioneer at the Broad Institute of MIT and Harvard, has garnered headlines lately for starting up Beam Therapeutics and raising $222 million to fund its research. Now, Zhang is rolling out his latest invention—a new strategy for editing RNA that his team says could someday be used to treat brain diseases like Alzheimer’s.

Zhang and colleagues developed a new system they call RNA Editing for Specific C to U Exchange (RESCUE). In cells, they used the technology to convert the gene variant APOE4—a risk factor for late-onset Alzheimer’s disease—into the non-pathogenic variant APOE2. They described the research in the journal Science.

CRISPR editing of DNA uses the enzyme Cas9 to snip DNA at specific locations. Targeting RNA instead can offer some advantages, because it avoids altering DNA permanently. Zhang’s team used a deactivated form of a different enzyme, Cas13, to target RNA.

RESCUE targets one of the four main “bases” of RNA, cytosine. Using a programmable enzyme, Zhang’s team converted pathogenic cytosine into uridine, which in turn changed the instructions RNA provided for, say, protein synthesis.

The researchers showed they could use RESCUE to target natural RNAs in cells, as well as “24 clinically relevant mutations in synthetic RNAs,” they said in a statement. They fine-tuned the technology to avoid off-target editing, a major concern that has slowed down the development of CRISPR for use in people.

Zhang’s team wanted to test RESCUE in Alzheimer’s because there are only two differences between the amino acid sequence for the risk variant APOE4 and that of the non-pathogenic APOE2. The used the technology to convert APOE4’s cytosines into an APOE2 sequence, effectively erasing the Alzheimer’s risk, they reported.

Another advantage of RNA editing is that it can be reversed. The MIT researchers showed in their study that they could use RESCUE to temporarily ramp up the activation of the protein beta-catenin, which could be useful in wound healing.

RESCUE builds on another system developed at the Broad called RNA Editing for Programmable A to I Replacement (REPAIR), which Zhang’s team reported in 2017. That technology changes the nucleoside adenosine (A) to inosine (I), which the researchers said could prove useful in treating diseases like Duchenne muscular dystrophy and Parkinson’s.

Several other research groups are working on RNA-editing technologies, including a team at the University of California, San Diego (UCSD), which used an RNA-targeted Cas9 system in lab models of myotonic dystrophy two years ago. A UCSD spinoff that’s developing the technology, Locana, raised $55 million in May of this year and is now working on tackling diseases like Huntington’s and amyotrophic lateral sclerosis.

The Broad’s Zhang says more work will have to be done before RESCUE can be tested in people. Meanwhile, he’s making the tool publicly available through the repository Addgene, so other researchers can use it to study disease-related mutations.

“To treat the diversity of genetic changes that cause disease, we need an array of precise technologies to choose from,” Zhang said in the statement. “By developing this new enzyme and combining it with the programmability and precision of CRISPR, we were able to fill a critical gap in the toolbox.”

https://www.fiercebiotech.com/research/crispr-pioneer-zhang-targets-brain-diseases-new-rna-editing-system

Mentally Stimulating Activities and Cognitive Impairment

The number of mentally stimulating activities adults participated in — and their timing — was tied to their risk of age-related memory loss, a prospective study of 2,000 older adults showed.

Engaging in two or more cognitively stimulating activities — such as reading books, computer use, crafts, social activities, and playing games — in late life was tied to a lower risk of incident mild cognitive impairment (MCI), reported Yonas Geda, MD, of the Mayo Clinic in Scottsdale, Arizona, and colleagues.

Engaging in any two activities in late life decreased MCI risk by 28%; three activities dropped the risk by 45%, and four activities lowered the risk by 56%, they wrote in Neurology.

“It is never too late,” Geda told MedPage Today. “If I am 84, I can still engage in mental activities and have good reason to assume I will have a better chance of reducing my risk of mild cognitive impairment.”

The analysis builds on the authors’ previous work that showed stimulating activities may diminish the risk of MCI in older people, even APOE4 carriers.

The earlier study generated a number of questions, noted co-author Janina Krell-Roesch, PhD, formerly of the Mayo Clinic and currently with the Karlsruhe Institute of Technology in Germany. In response, “this new research looked at two different things,” she told MedPage Today. “Does the timing of the activities matter? And does the number of activities matter?”

The current research followed 2,000 cognitively unimpaired people who were ages ≥70 in the Mayo Clinic Study of Aging, monitoring them for clinical progression to MCI over a median of 5 years. Participants completed a self-reported survey at baseline about the timing, number, and frequency of engaging in five mentally stimulating activities: reading books, computer use, social activities, playing games, and craft activities.

At baseline, participants had a median age of about 78 and education level of 14 years. Half of the group (49.9%) was male. Over the follow-up period, 532 people developed new onset MCI.

The number of mentally stimulating activities participants engaged in at midlife (from the ages of 50 through 65) showed no significant association with the risk of new onset of MCI. But in late life (ages ≥66), engaging in more activities was tied to a significantly reduced risk of incident MCI.

Engaging in any two activities in late life showed an HR for MCI of 0.72 (95% CI 0.53-0.99). Engaging in any three late-life activities had an HR of 0.55 (95% CI 0.40-0.77), four activities showed an HR of 0.44 (95% 0.30-0.65), and five had an HR of 0.57 (95% CI 0.34-0.96).

Computer use in midlife, computer use and craft activities in late life, and social activities, game playing, and computer use in combined late-life and midlife stages all were linked to a decreased incidence of MCI. In late life, a decreased risk of MCI was tied to reading books, playing games, or engaging in craft or social activities at least 2 to 3 times a month, or using a computer at least 5 to 6 times a week.

This analysis provides “evidence that there is an association between quality and quantity of mentally stimulating activities, which include both cognitive and social leisure activities, and reduced risk or slowing of the emergence of mild cognitive impairment,” noted Rebecca Amariglio, PhD, of Brigham and Women’s Hospital in Boston, and colleagues, in an accompanying editorial.

“The findings of this report could be of value to clinicians attempting to counsel midlife and older adults about how to stave off or delay the onset of mild cognitive impairment,” they added. While mentally stimulating activities may be low-cost interventions that could decrease the risk of cognitive decline,” important questions remain about why mentally stimulating activities remain primarily more protective in late life compared with midlife.”

The study has several limitations: it was observational and did not provide evidence that cognitively stimulating activities reduce incident cognitive impairment. Low engagement in activities may be the result of incipient MCI; other unmeasured variables also may account for the associations found in the study. Activities were self-reported and participants were asked to remember how often they engaged in activities as far back as middle-age, up to 2 decades before the study began.

Last Updated July 10, 2019

The study was supported by the NIH, the National Institute on Aging, the National Institute of Mental Health, the Robert Wood Johnson Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program, the GHR Foundation, the Mayo Foundation for Medical Education and Research, the Edli Foundation, and the Arizona Alzheimer’s Consortium.

Researchers disclosed relevant relationships with Eli Lilly, Lysosomal Therapeutics, Biogen, Lundbeck, the Alzheimer’s Treatment and Research Institute, AstraZeneca, Roche, Merck, Genentech, and Janssen Alzheimer Immunotherapy.

The editorialists disclosed no relevant relationships with industry.

Primary Source

Neurology

Source Reference: Krell-Roesch J, et al “Quantity and quality of mental activities and the risk of incident mild cognitive impairment” Neurology 2019; DOI: 10.1212/WNL.0000000000007897.

Secondary Source

Neurology

Source Reference: Skylar-Scott I, et al “Frequency, number, and timing of mental activity and risk of mild cognitive impairment” Neurology 2019; DOI: 10.1212/WNL.0000000000007890.

https://www.medpagetoday.com/neurology/dementia/80942

Indivior fights off generic challenges but the threat of litigation remains

Today’s 16% rise in Indivior’s share price has less to do with the group selling more of its opioid dependency treatment products than with the inability of its generic competitors to sell theirs.

Indivor thrilled the market with substantially upgraded full-year guidance for 2019, as it appeared that generics companies like Dr Reddy’s and Mylan had failed to convince patients to try their version of Indivior’s Suboxone film. The product, which has continued to defy conventional wisdom around generic sales erosion, still accounts for the majority of Indivior sales.

Another demonstration of Suboxone’s continued grip on the US opioid substitution market is that the product still makes up over 70% of opioid substitution products. This figure includes the 24% of sales contributed by the authorised generic Indivior launched in February as a countermeasure to copycats.

Despite the strong showing today Indivior’s shares, which have been falling since June 2018 when the FDA approved generic versions of Suboxone film, are still down 55% on the year.

Settling for a billion

Indivior’s guidance came on the same day that its former parent, Reckitt Benckiser, announced that it had reached an agreement with the Department of Justice and Federal Trade Commission to pay up to $1.4bn to settle claims it had participated in fraudulent marketing schemes to increase sales of Suboxone.

As the current owner of Suboxone, Indivior was also named in the investigation. But the UK company has denied the allegations, which it has described as “self-serving” and based on events four years before Indivior was spun out of Reckitt in 2014.

Reckitt’s $1.4bn settlement is one of the biggest the industry has seen, though it is still eclipsed by Glaxosmithkline’s eye-watering $3bn payout for failing to disclose safety information around diabetes drug Avandia.

Read-through?

While it might not be pharma’s largest payout, $1.4bn is still a large amount of money even if the compay on the hook for it has a market cap of £47bn. And here is the rub for Indivior, which for litigation purposes has far shallower pockets than Reckitt. So far Indivior, which only has a market cap of £389m ($480m), has set aside $438m for any form of payout.

Indivior has also chosen to go to trial to refute the DoJ/FTC allegations. A hearing is not expected until 2020 and could take up to two years to conclude, meaning any overhang to Indivior shares could continue for another three years.

But what today’s announcement by Reckitt shows is that it is possible to settle with the DoJ without any requirement to admit wrongdoing. This non-prosecution type agreement is important if Indivior wants to retain its current access to US government Medicare and Medicaid contracts, which currently represent around half of its US business.

As to the size of any settlement for which Indivior might be liable, some analysts are not expecting the amount forked out by Reckitt, which would effectively bankrupt Indivior. “The DoJ knows that they are not going to get $1.5bn out of Indivior, but they might get a bit more than what Indivior has set aside. If they can get $600m or $700m and settle then everyone can move on,” said one healthcare analyst.

Until then, despite its success in holding off the more immediate generic threats, Indivior will still remain a tricky investment case.

https://www.evaluate.com/vantage/articles/news/indivior-fights-generic-challenges-threat-litigation-remains-0

Soliton Expands Clinical Trial Sites to include Skin Care Physicians

Soliton, Inc. (SOLY) (“Soliton” or the “Company”), a medical device company with a novel and proprietary platform technology licensed from The University of Texas on behalf of the MD Anderson Cancer Center (“MD Anderson”), today announced that the company has identified an additional site and supervising physician for its upcoming expanded pivotal Cellulite Trial. The site is the second of four planned sites for the pivotal trial.

The proof-of-concept trial was conducted by Dr. Michael S. Kaminer at SkinCare Physicians in Boston in collaboration with Dr. Elizabeth L. Tanzi of Capital Laser and SkinCare in Chevy Chase, MD. The expanded Cellulite Clinical Trial will now include subjects treated at SkinCare Physicians, supervised by Dr. Kaminer, added to the subjects being treated at Capital Laser. Drs. Kaminer and Tanzi are members of the Company’s Scientific Advisory Board.

https://finance.yahoo.com/news/soliton-expands-clinical-trial-sites-120000888.html