Amazon refutes medical purchase cuts

Amazon (AMZN -0.5%) hits back at a UBS report earlier this week alleging hospitals have cut back on medical supply purchases from the e-commerce giant.

In a statement to Bloomberg, Amazon says that “healthcare customers continue to purchase through Amazon Business across multiple categories for their workplace needs.”

Related: A Morgan Stanley survey showed the percentage of hospitals that purchased from Amazon rose to 77% in Q2 compared to the 65-70% of prior surveys.

https://seekingalpha.com/news/3477245-amazon-refutes-medical-purchase-cuts

Illumina down 15% after hours on softer guidance

Illumina (NASDAQ:ILMN) slumps 15% after hours in reaction to its preliminary Q2 revenue, expected to be ~$835M, up less than 1% from a year ago ($830M) and below consensus of $888M. The less-than-expected growth was due to a large sequencing system order that failed to close, persistent weakness in the direct-to-consumer market and modest weakness in non-high-throughput systems.

As a result, management has lowered its 2019 revenue growth guidance to ~6% from 13 – 14%.

Sequencing revenue should grow ~10%, but its array business will be down ~14%. NovaSeq system shipments will be flat/slightly up from a year ago.

Its Q2 earnings call will be after the close on Monday, July 29.

https://seekingalpha.com/news/3477256-illumina-15-percent-hours-softer-guidance

CMS announces 5 new payment models aimed at kidney care

The Trump administration Wednesday unveiled five new payment models aimed at transforming kidney care—including one that would be mandatory for some providers.

The End-Stage Renal Disease (ESRD) Treatment Choices model will launch Jan.1. The Centers for Medicare & Medicaid Services (CMS) announced that certain ESRD treatment facilities and clinicians who manage care for beneficiaries with this condition will be required to participate, based on their location, which will be randomly selected.

Under the model, CMS intends to adjust payments to these providers either upward or downward based on their home dialysis and transplantation rates, with the aim of reducing the focus on clinic dialysis, officials said.

CMS is aiming to enroll providers that represent half of Medicare beneficiaries with ESRD in the model. On a call with reporters Wednesday morning, Adam Boehler, director of the Center for Medicare and Medicaid Innovation, likened the new models to another recent initiative, Primary Cares—both are “broad and sweeping,” he said.

“We will do more to create appropriate incentives,” CMS Administrator Seema Verma said on the call.

Today’s announcement is about turning the page on #kidney disease, for the first time in 50 years to a new chapter that focuses on improving quality of care, quality of life, & improving health outcomes for the 430,000 people with kidney disease in #Medicare.

— Administrator Seema Verma (@SeemaCMS) July 10, 2019

A significant amount of Medicare spending goes to dialysis and kidney care. It encompasses $114 billion in Medicare dollars, about 20% of the program’s total spending. About 37 million people have kidney disease.

The other four models will be voluntary demonstrations, according to CMS. In the first, called Kidney Care First, nephrology practices will be offered fixed payments on a per-patient basis for managing ESRD, and those payments will be adjusted based on outcomes and performance.

The remaining models fall under the Comprehensive Kidney Care Contracting program, which includes three tracks: graduated, professional and global. These models are aimed at other kidney care providers, such as dialysis centers and transplantation units, as well as nephrologists.

Under these models, the provider will take full responsibility for care cost and quality, and in return can earn back some of the Medicare savings they achieve, CMS said.

The voluntary models will also launch Jan. 1, CMS said, and the agency reserves the option to extend any of the five by two to three years.

The new payment models are a key initiative within an executive order signed Wednesday by President Donald Trump that aims to improve kidney care. The order has three central goals: prevent people from developing kidney failure, boost access to in-home dialysis and make more kidneys available for transplants.

The order outlines several bold goals, including reducing the number of Americans who develop ESRD by 25% by 2030 and having 80% of new ESRD patients receiving dialysis at home or a transplant by 2025.

In a speech, Trump said the order was “groundbreaking action” and that making in-home dialysis more available was a crucial step.

“Doing this from home is a dramatic, long-overdue reform, that people have been asking for for many, many years,” the president said.

Administration officials including Department of Health and Human Services Secretary Alex Azar have teased some of these initiatives in prior speeches.

Joe Grogan, director of the White House’s Domestic Policy Council, said on the call that the steps announced Wednesday align closely with the president’s priorities. “This sits deeply in the wheelhouse of the type of problems the president likes to” tackle, he said.

In addition to the payment models, the executive order pushes for education on kidney care to boost prevention, greater supports for living kidney donors and a slew of other proposals.

Kidney Care Partners, the largest kidney care coalition group, said in a statement that it welcomes the administration’s focus on nephrology.

“KCP praises the administration’s ‘bold’ steps and fresh thinking about this important and often overlooked segment of healthcare patients,” the group said.

In a statement, DaVita, the largest kidney care provider in the U.S., said it’s in the strongest position to lead the charge on in-home dialysis.

“DaVita is encouraged that this administration has taken steps toward holistic, value-based care for kidney patients. We have pushed for progressive policies to give all patients access to integrated kidney care, the benefits of which are significant to our patient population,” DaVita CEO Javier Rodriguez said. “Educating patients about kidney disease is critical to prevention and slowing its progression. Early intervention leads patients who may still need dialysis to choose the best treatment option for their lifestyle and reduces expensive hospitalizations. ”

Fresenius Medical Care, the world’s largest provider of dialysis services and products, called the EO a “win” for its patients.

https://www.fiercehealthcare.com/regulatory/cms-announces-five-new-payment-models-aimed-at-kidney-care

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