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Wednesday, December 11, 2019

Hospital leaders increasingly open to negotiated price caps

With Democrats debating Medicare for All and public-option health plans, healthcare CEOs have become surprisingly open to the idea of negotiated caps on provider payment rates, according to Modern Healthcare’s latest Power Panel survey.
While expressing strong misgivings about those Democratic reform proposals, 75% of CEOs responding to the survey last month said their organization could live with some form of price caps as long as their industry had the opportunity to negotiate reasonable levels.
“There has been a change in thinking about payment caps over the last five years,” said Howard Kern, CEO of Sentara Healthcare. “The industry can’t be out there setting outrageous prices. We have to be prepared to set rates that are reasonable. But all the players, including pharma, have to be playing under the same rules.”
Price caps are only one of a number of major policy challenges and opportunities the CEOs anticipate facing depending on the outcome of the 2020 presidential and congressional elections.
The survey was based on a small sample size, with 12 healthcare CEOs responding. Those surveyed overwhelmingly see federal health policy currently moving in the wrong direction.
In contrast, after the election they want to see action on expanding and strengthening the Affordable Care Act, controlling prescription drug prices, and boosting funding for mental health and addiction treatment. About 42% of those responding said the election will have a major impact on their industry. “This may be one of the most significant elections for healthcare in a very long time,” said Chris Van Gorder, CEO of Scripps Health, citing the possibility of victorious Democrats establishing a single-payer government health insurance system, which he opposes.
Half of respondents said the election outcome will have only a modest impact, though some said that with the expectation that voters are unlikely to give either party commanding control of Congress and the ability to pass ambitious legislation.
“Drug prices have got to be addressed, but there will have to be some alignment between the Senate and the House to get that done,” Kern said.
Van Gorder agreed that curbing drug prices is critical, particularly as value-based payment grows. “Some drugs are so expensive that they could destroy the value-based plan with just a few patients needing that therapy,” he said. “We need some frames around those costs.”
The healthcare executives are deeply worried about what will happen if the courts strike down the ACA as unconstitutional, in response to a lawsuit filed by Republican attorneys general and backed by the Trump administration. A ruling in that case is expected soon from the conservative-dominated 5th U.S. Circuit Court of Appeals, after which an appeal to the U.S. Supreme Court is likely no matter the decision.
Difficult to fathom
Still, the CEOs have a hard time imagining either the courts or federal elected officials erasing the most popular provisions of the law, such as expanding Medicaid to low-income adults. Most predicted that if the courts topple the ACA, Congress will reenact it with slight changes to pass constitutional muster.
“If the ACA is struck down without a plan to replace it, we’re in deep trouble in this country,” said Dr. Gary Kaplan, CEO of Virginia Mason Health System. “All those provisions for coverage, pre-existing condition protections, and keeping children on their parents’ health plan have become norms. We have to be prepared to reenact legislation.”
CEOs interviewed for this article had different views of Democratic proposals to establish cheaper public-option health plans to compete with private insurers, which some experts consider a more politically viable approach than Medicare for All.
Peter Fine, CEO of Banner Health, warned that public-option plans likely would underpay providers and disrupt the healthcare system. “We have to make big investments on a long-term horizon,” he said. “When we see a significant level of disruption, does that make us nervous? You bet it does.”
In contrast, Kaplan sees some form of a public-option plan that pays reasonable rates and moves the U.S. toward universal coverage as desirable. In Washington state, where his system operates, public-option plans administered by private insurers and paying hospitals about 160% of Medicare rates are slated to hit the market in 2021, under a state law passed this year.
Still, he cautions that the public-option plans have to pay more than Medicare, and that rates need to be set through a collaborative effort between government, health plans and providers.
“There are huge disparities in commercial rates and there could be some advantages if those payments are leveled out, particularly for those who don’t have pricing power in the market,” he said.
Billing legislation expected to hurt
Half of CEOs surveyed said current bipartisan congressional efforts to protect patients from surprise, out-of-network bills would have a negative impact on their organizations.
While they support the idea of shielding patients from such bills, they oppose the idea of capping out-of-network rates. They’d prefer an arbitration process between providers and payers.
“If you set the price cap for out-of-network care in the emergency room at 150% of Medicare, we would lose millions,” said Van Gorder, whose state already caps out-of-network rates but not for self-insured plans. “And it would take away the incentive of insurers to negotiate a fair rate. That’s why insurers are advocating for this.”
Shifting Medicaid financing to a capped federal payment model, which the Trump administration and congressional Republicans strongly support, is another proposal that 75% of CEOs said would have a negative effect on their organizations. That’s a direction Republicans are likely to go if they win the elections.
But one CEO said much depends on the complex details of how a Medicaid block grant or per-capita cap model is designed.
“We could be very receptive to a block-grant approach giving us more flexibility to manage Medicaid patients,” said Kern, whose organization offers health plans serving people dually eligible for Medicaid and Medicare. “But I am worried the feds will look for the states to pick up a bigger share of the costs of seniors on Medicaid.”
ACA backup plan TBD
Meanwhile, the CEOs said they are not making any contingency plans for the ACA being thrown out or for the next Congress to pass a major healthcare overhaul like Medicare for All. Instead, they are focusing on delivering high-quality care and innovating to increase the value of the care they provide.
“We won’t react to every fear or piece of legislation,” Van Gorder said. “If we did that, we would drive the organization absolutely nuts. I get up every day worrying about whether we’re going to deliver good care to the patient in the trauma room. I worry less about what legislators are doing in Washington or Sacramento.”
The CEOs interviewed all lamented the partisan-driven reversals in health policy over the past decade. They guardedly hope that Republicans and Democrats after the 2020 elections will move forward together on the nation’s health goals.
“Had Republicans and Democrats worked together to fix the ACA, we wouldn’t be talking now about radical approaches that I don’t think will work,” Van Gorder said. “After the election I’m highly skeptical that will happen. But I’d like to think it will.”

SABCS 2019 – Astrazeneca and Daiichi join the Her2 resistance

New data confirms that trastuzumab deruxtecan has an exciting destiny, but the antibody-drug conjugate’s impressive efficacy in late-stage breast cancer comes at a price.

Trastuzumab deruxtecan, the antibody-drug conjugate being developed for breast cancer by Astrazeneca and Daiichi, is forecast to be one of the biggest launches of 2020. The strength of today’s data from the phase II Destiny-Breast01 trial, unveiled at the San Antonio Breast Cancer Symposium, suggest that the substantial expectations are justified.
This sting in the tail is safety, however. The results confirm that the ADC can cause serious toxicities, with 14% of patients in the study suffering interstitial lung disease, four whom died of the complication, with their deaths deemed treatment-related. But with an impressive 61% of heavily pre-treated patients responding to the therapy, this issue seems unlikely to derail the project’s approval chances.
This is impressive in a population that had had a median six prior lines of cancer therapy including Roche’s ADC Kadcyla. As a single-arm study there are limitations to this data, but investigators noted that the results stand out in a very crowded field.
“To put it in context, progression-free survival of 16 months [and] response rate of 60% – those are roughly double or triple what typically we’ve seen in other studies of this third- and later-line population,” Dr Ian Krop of the Dana-Farber Cancer Institute said in a press conference. Overall survival was not reached.
PHASE II TRIAL (DESTINY-BREAST01)PHASE I TRIAL (DS8201-A-J101)
Response rateN
(184 in study)
Response rateN
(118 in study)
Confirmed ORR (primary endpoint)60.9%11259.5%66
     Complete response6.0%11
     Partial response54.9%101
Disease control rate (CR+PR+SD)97.3%93.7%
Median progression-free survival16.4 months22.1 months
Median duration of response14.8 months20.7 months
Median prior lines of cancer therapy6 (range 2-27)7
Rate of interstitial lung disease*13.6%2516.9%20
* in phase I trial this includes ILD, pneumonitis or organising pneumonia. Source: Ian Krop & SABCS; NEJM, The Lancet.
In an earlier phase I study trastuzumab deruxtecan managed an objective response rate of 60% in Her2-positive breast cancer patients previously treated with an average of seven therapies including Kadcyla. At the time, Astra called that achievement “unprecedented”, and this larger trial has largely replicated the findings of that work (Astra and Daiichi lay out their plan for a better Herceptin, May 8, 2019).
The current treatment sequence for metastatic Her2-positive disease is dominated by three Roche products. First-line treatment with a taxane plus Herceptin plus Perjeta; second-line treatment is generally Kadcyla. There is no consensus on the best therapy for the third-line setting.
The response rate to trastuzumab deruxtecan in Destiny-Breast01 was particularly notable among patients previously treated with Perjeta: 64.5% of these responded compared with 54% who had never received Roche’s drug.

Waterfall graph of change in tumour size with trastuzumab deruxtecan
Source: Ian Krop & SABCS.
Trastuzumab deruxtecan’s Achilles heel is its side-effect of interstitial lung disease. This was seen in 13.6% of the Destiny-Breast01 patients, a slight improvement from the rate in phase I, but still a drawback that could lead to a black box warning on any future label. Dr Krop conceded that the rates of interstitial lung disease were higher than seen in studies of other drugs, including Herceptin and Kadcyla. He added that the investigators could not explain this, particularly since ADCs are supposed to allow the specific targeting of tumours. This side-effect will require careful monitoring.
The project is due a US decision on its BLA for third-line breast cancer in the first quarter of next year. The sellside has already pencilled in some huge sales numbers that make the ADC one of the sector’s most valuable oncology assets currently in development. EvaluatePharma‘s consensus has sales topping $2bn by 2024 and some analysts have mooted peak sales of $7bn, though this all relies on trastuzumab deruxtecan proving its worth in earlier settings. Presumably these are the kind of revenues Astra was anticipating when it paid $1.4bn up front to license the drug (Astra shakes hands with Daiichi to take on Roche, March 29, 2019).
Moreover, there are plenty of other next-gen Her2s following behind. Data on Seattle Genetics’ TKI tucatinib and Macrogenics’ margetuximab are also expected at SABCS, and there are plenty of others working on a “better Herceptin” (SITC 2019 preview – Pieris joins the quest for a better Herceptin, November 4, 2019).
If one of these competing agents can come close to trastuzumab deruxtecan’s efficacy without its safety signal, expectations might have to be reined in. But for now, this is the project to beat.

FDA Panel Friday for Horizon’s teprotumumab for thyroid eye disease

The FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee will meet on Friday, December 13, to review and discuss Horizon Therapeutics’ (HZNP +0.8%) marketing application for lead drug teprotumumab for thyroid eye disease.

Twist Bioscience EPS misses by $0.11, beats on revenue

Twist Bioscience (NASDAQ:TWST): Q4 GAAP EPS of -$0.96 misses by $0.11.
Revenue of $15.74M (+87.2% Y/Y) beats by $1.69M.

Tonix Pharma nabs European patent covering TNX-102 SL

Nano cap Tonix Pharmaceuticals (NASDAQ:TNXP) is up 22% after hours in reaction to its receipt of a new composition of matter patent in Europe covering TNX-102 SL.

Gilead files U.S. application for CAR T for mantle cell lymphoma

Gilead Sciences (NASDAQ:GILD) unit Kite has submitted a marketing application to the FDA seeking approval for CAR T therapy KTE-X19 for the treatment of adults with relapsed/refractory mantle cell lymphoma, a type of slow-growing NHL.
The company plans to file an application in Europe next quarter.

Single Shot of Ketamine May Herald ‘Last Call’ for Problem Drinking

An experimental treatment that includes a single infusion of ketamine may lead to long-term improvement in problem drinking, new research suggests.
In an study of 90 heavy drinkers, those who received a single dose of intravenous (IV) ketamine plus cognitive behavioral therapy (CBT) that focused on reactivating drinking-related “maladaptive reward memories” (MRMs) significantly curbed the urge to drink and reduced alcohol intake  compared with those who received the ketamine alone or a placebo infusion.
In addition, the combination group reduced their average weekly alcohol consumption by 50% over 9 months of follow-up.
MRMs can cause the brain’s reward-learning system to produce an exaggerated desire to take a drug. However, the ketamine plus CBT intervention worked to “reboot” the brain, in order to relearn healthy associations. “This is a first demonstration of a very simple approach,” lead investigator Ravi Das, PhD, associate professor, University College London (UCL) Clinical Psychopharmacology Unit, United Kingdom, told Medscape Medical News.
“We hope that with more research into optimizing the method, this could turn into a helpful treatment for excessive drinking, or potentially for other drug addictions,” Ravi added in a statement.
The findings were published online November 26 in Nature Communications.

Hijacking the Brain

MRMs are “central to drug and alcohol addiction,” the investigators note.
Drug abuse “hijacks the brain’s in-built reward-learning system so that you end up associating environmental ‘triggers’ with the drug,” Das said.
“Unfortunately, once these reward memories are established, it’s very difficult to re-learn more healthy associations, but it’s vital in order to prevent relapse,” he added. “We were interested in the processes underlying why people react and the main thing seems to be these learned responses to their environment.”
“It’s a bit like Pavlov’s dog,” a famous research subject who learned to associate the reward of food with the ringing of a bell, which induced salivation, he said.
“Humans have the same kind of automatic learning process. So we were looking at ways to break those associations, and one of the most promising methods is this process of memory reconsolidation,” Das added.
In addition, because destabilized memories rely on an N-methyl D-aspartate receptor (NMDAR) mediated protein cascade to re-stabilize themselves, adjunctive ketamine, an NMDAR antagonist, was added to the protocol.
“The main reason we were interested in using ketamine is because we knew it blocks this receptor. And we thought we could use it as a tool to weaken alcohol memories,” Das said.

Heavy Drinkers

Ninety individuals (61% men; mean age, 27.5 years) with harmful drinking behavior, but without a formal diagnosis of alcohol use disorder, were enrolled in the study. All had a score greater than 8 on the Alcohol Use Disorders Identification Test.
Participants consumed an average of 74 units of alcohol (8 g) per week, five times the recommended limit. Participants preferred beer, and so 74 units was the equivalent of 30 pints of beer per week.
In the study, all were given a glass of beer, told they could not drink it until they finished a task, and were then asked to rate the intensity of their urge to drink.
Participants also rated their anticipated pleasure after seeing images of beer and other alcoholic drinks. This process focused on retrieving reward memories associated with beer drinking.
Baseline drinking urges were determined on Day 1 when the participants were permitted to drink the beer. On Day 3, the beer was unexpectedly taken away in order to destabilize a retrieved reward memory.
“Typically the brain would then undergo an active process to re-stabilize and store the memory. However, ketamine prevents this memory re-storage process by blocking a receptor in the brain needed to re-stabilize memories,” the researchers noted in the release.
Immediately after the beer was removed, one third of study participants received an IV infusion of ketamine hydrochloride, while another third received a saline placebo infusion. The remaining third received the ketamine infusion but without going through the memory retrieval procedure. All participants underwent blood draws before, and after, the infusions.

Long-Term Improvement

Results at the 10-day follow-up showed that compared with the other two groups, the ketamine plus memory retrieval group had significant reductions in “urge to drink” ratings (P  .007).
They also showed pre-drink reductions in their anticipated enjoyment of beer (P < .001) and in actual enjoyment after drinking the beer (P = .004). They also experienced a reduction in weekly alcohol consumption (P < .001), and had a significant reduction in binges, defined as more than 6 drinks per weeks (P < .001).
All three groups decreased their drinking behavior over the 9-month follow-up period. However, the ketamine plus memory retrieval group had greater initial improvement than the other groups, and a greater overall improvement over time.
Both ketamine groups significantly reduced their drinking volume at the 9-month assessment, but only the combination group lowered their total number of drinking days and bingeing behavior.
Finally, blood levels of ketamine predicted beneficial changes in drinking behaviors — but only after MRM reactivation.
Overall, “we found that heavy drinkers experienced a long-term improvement after a very quick and simple experimental treatment,” Das said.
“An advantage of our study, alongside the pronounced, long-term effect on drinking, is that it’s based on a strong understanding of how the drug is working in the brain to achieve its effect,” senior author Sunjeev Kamboj, also from the UCL Clinical Psychopharmacology Unit, said in the release.
Das admitted that he was somewhat surprised that the process worked.
“I’ve been doing research in this field for about 10 years and you get used to expecting not much because getting people to change their behavior around drug use is very difficult,” he said.
So seeing their findings was a pleasant surprise, Das noted. However, he cautioned that this is still an experimental procedure and more research is needed before any recommendations can be made.
In addition to looking into whether they can replicate the findings in a large clinical trial, the investigators hope to assess whether other, more noninvasive drugs may be helpful and whether the treatment regimen is effective in conditions such as posttraumatic stress disorder.

“Promising Hypothesis”

Commenting on the study for Medscape Medical News, George Koob, PhD, director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), said the findings “open a promising hypothesis” that should be tested further.
George Koob, PhD
“There are multiple aspects of treatment for alcohol use disorder, one of which is behavioral treatments,” Koob said. If the results of this bear out in other studies, this particular intervention “could be a great add-on to the armamentarium,” he said.
“Similarly, we’re always looking for medications that will help. And both of those are woven into the fabric of this paper,” Koob said.
However, he added that ketamine can be a major drug of abuse.
“Ketamine itself may not be the ‘drug of drugs,’ but the target that they are hypothesizing, working through the glutamatergic system, may indeed be a very good target,” Koob said.
He noted that the behavioral part of the investigators’ process has demonstrated efficacy in animal studies.
“So this is a very nice confirmation that you can trigger craving and, by manipulating that craving, decrease drinking in humans,” he said.
Koob added that the combination of a behavioral therapy, of which there could be others, plus a drug “could be potentially powerful.”
The study was funded by the Medical Research Council. The study authors and Koob have disclosed no relevant financial relationships.
Nat Commun. Published online November 26, 2019. Full text