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Friday, January 17, 2020

MedPAC finds 340B effect on pricing ‘modest,’ going against pharma critique

  • A Medicare Payment Advisory Commission study found spending on cancer drugs at hospitals participating in the 340B drug discount program was only 2% to 5% higher than non-340B hospitals and 1% to 7% higher than physician offices. The overall effect of the controversial program on cost-sharing for patients is “likely to be small, if any,” the Congressional advisory group said.
  • Researchers were careful to point out they couldn’t directly attribute the spike in costs to incentives created by 340B discounts, noting another potential explanation is that 340B hospitals are more likely to be large teaching hospitals and care for outsized numbers of young and disabled patients who require aggressive treatment and receive subsidies in Medicare’s prescription drug benefit.
  • The findings, described as “inconclusive” by one MedPAC member, throw cold water on big pharma’s perennial complaint that the program, established in 1992 to lower drug prices for safety net hospitals, is a major driver of healthcare spending.

Hospitals participating in the 340B program can buy outpatient drugs at substantial discounts, using the average sales price of the drug minus a rebate that changes based on inflation and whether the drug is branded or generic.
Empirical evidence on 340B, which gives participating hospitals on average a 25% to 50% discount on medicines, is limited. House Committee on Energy and Commerce Chairman Frank Pallone, D-N.J., asked MedPAC to dig into the drug discount program’s effect on healthcare spending in 2018. Its initial findings made public Friday provides some new ammunition in the ongoing battle between pharmaceutical companies and nonprofit disproportionate share hospitals over the future of 340B.
Eligible hospitals say they need the program in order to stay afloat, and that big pharma loathes it because it nibbles away at profits. Pharmaceutical companies riposte 340B pads hospitals’ bottoms lines, trickling down to higher costs for patients.
MedPAC’s analysis, one of the few from a non-pharma or non-provider funded angle, looked at monthly average cancer drug spending in 340B hospitals, non-340B hospitals and physician offices across five types of cancer: breast, colorectal, prostate, lung, leukemia and lymphoma.
Higher spending at 340B hospitals seems to be linked to the specific form of cancer. The 340B program was associated with higher spending for just two of the five cancer types studied: prostate and lung, MedPAC researchers found. However, the effects of general increases in oncology spending from 2009 to 2017 and patient age both had large statistically significant effects on cancer spend.
Lung cancer, which accounts for one-fourth of cancer deaths, usually has a higher price per unit for drugs in Medicare Part B, and a larger swath of the patient population is likely to receive new, pricey immuno-oncology drugs if treated in 340B hospitals. Prostate cancer also has a higher price per unit in both Medicare Part B and Part D, and patients are prescribed more drugs in 340B hospitals than non-340B facilities.
However, none of those findings were directly attributable to incentives created by discounts in the 340B program, researchers cautioned, and can’t be generalized to other cancers or conditions, deflating the drug lobby’s common attack that 340B incentivizes hospitals to choose higher priced drugs and use more drugs to inflate their margins.
“These results are a little surprising because they’re not that strong,” Lawrence Casalino, a MedPAC member and health policy chief at the Weill Cornell Department of Healthcare Policy and Research, said at the group’s Friday meeting, while Oschsner Health System CEO Warner Thomas shrugged them off as “modest” and “somewhat inconclusive.”
Powerful trade group PhRMA has been actively trying to shift public opinion on 340B through a barrage of reports and studies over the past few years.
A PhRMA-commissioned late last year argued safety net hospitals in the program were reimbursed for physician-administered drugs at three times higher than what they paid, and another found the program costs patients more in the long run by moving care away from physician offices to more expensive hospital outpatient settings. Some lawmakers have been similarly concerned about price and lack of government oversight or transparency, inciting MedPAC’s inquiry into 340B.
Friday’s report​ looked at the program prior to 2018, when CMS drastically overhauled payments in the program. Instead of hospitals receiving a drug’s average sales price plus 6%, they were paid 22.5% less than the average price. The facelift immediately sparked a legal challenge that was litigated for much of last year, with renewed fervor after CMS decided to continue the cuts going into 2020 despite a previous court ruling striking them down.
The case is now in the D.C. Circuit, with a decision expected this summer.
Commissioners asked Friday for more information on how consolidation and other environmental trends, like Medicaid expansion, contributed to the spread of 340B. “Is there any other consolidation that preceded this status? Are hospitals seeing it as a windfall” and buying 340B facilities to participate, asked MedPAC commissioner and University of Pennsylvania Health Transformation Director Amol Navathe.
Despite the hullabaloo, advocates for 340B maintain its benefits for low-income patients and their providers outweigh any drawbacks.
The program saved hospitals $11.8 million in 2018, according to trade group 340B Health, which said 90% of those savings was used for patient care services. A strong majority of hospitals said losing those savings would stop them from being able to provide programs like pharmacy services and transportations, with rural hospitals arguing it would contribute to hospital closures, worsening care access in needy areas.

Qiagen up 4% on renewed takeover chatter

QIAGEN N.V. (QGEN +4.3%) is up on almost double normal volume amid new rumors of a potential suitor.
Shares rallied last quarter on the same chatter but shares plunged in December after the company decided to remain independent.

$8B Risperdal award against Johnson & Johnson cut to $6.8M

Judge Kenneth Powell of the Philadelphia Court of Common Pleas reduced the payout that a jury awarded Oct. 8 to the plaintiff Nicholas Murray, a Maryland resident.
No reason was given for the reduction, which was disclosed in court records. Lawyers for Murray have said the punitive damages award was the first in thousands of lawsuits against Johnson & Johnson’s Janssen Pharmaceuticals unit over Risperdal.
Murray claimed he had been prescribed the drug in 2003, when he was 9, to treat symptoms related to autism. He had previously been awarded $680,000 in compensatory damages.
Both sides pledged to appeal.
“The ruling is wrong (and) provides essentially no punishment for the worst of the worst of corporate misconduct,” Murray’s lawyer Thomas Kline said in an email. “We believe that when the merits are reviewed that the $8 billion will be reinstated.”
Johnson & Johnson said that while Powell “appropriately reduced the excessive punitive damages award,” he wrongly excluded evidence that Risperdal’s label “clearly and appropriately” outlined the risks of use.
The U.S. Food and Drug Administration approved Risperdal in 1993 to treat schizophrenia and bipolar mania in adults, and in 2006 for irritability associated with autism in children.
Plaintiffs suing over the drug have said Johnson & Johnson concealed the link between Risperdal and excessive growth of female breast tissue in boys, known as gynecomastia.
While doctors may prescribe many drugs as they see fit, including for off-label uses, Murray said Johnson & Johnson should have warned his doctors about Risperdal’s side effects.
Johnson & Johnson said in October it faced lawsuits by 13,600 people over Risperdal.
The New Brunswick, New Jersey-based company agreed separately in 2013 to pay $2.2 billion to settle U.S. criminal and civil probes into its marketing of Risperdal and two other drugs.

While expected, Intercept’s approval delay adds to NASH uncertainty

In a Friday disclosure, Intercept Pharmaceuticals said it could take up to three months longer for regulators to make an approval decision on the company’s closely watched liver disease drug. The approval deadline is now set for June 26 rather than March 26.
Intercept expected such a delay due to the scheduling of an upcoming Food and Drug Administration meeting. Slotted for April 22, the meeting will have a panel of independent experts evaluate Intercept’s drug as a treatment for the disease, and then recommend to the FDA whether its safety and efficacy support approval. Given the timing, it was fairly certain an approval decision would be pushed back until after the panel makes its recommendation.
Despite the delay, Intercept CEO Mark Pruzanski maintains that his company’s drug, called obeticholic acid, can enter the U.S. market before the end of June.
“I feel very confident that we will be ready and we will be able to drive the successful launch of this drug,” Pruzanski told BioPharma Dive during an interview Wednesday, right before Intercept was notified of the new approval deadline. The company confirmed Friday that it’s still guiding for a U.S. approval and launch in the first half of 2020.
Intercept’s drug has already gotten the FDA’s blessing for a separate condition called primary biliary cholangitis, for which it is marketed as Ocaliva.
If approved again, it would be the first commercial treatment for non-alcoholic steatohepatitis, a fatty liver illness estimated to affect millions of U.S. patients. The large market opportunity has made NASH a crowded area of drug development, with big players such as Pfizer, Novartis and Gilead investing heavily.
Intercept, however, is the only one to have succeeded in a late-stage clinical trial. Results showed that NASH patients with moderate to advanced liver scarring who were put on Intercept’s drug ended up experiencing a one-stage-or-greater improvement in fibrosis without their disease worsening.
This effect, though, was seen in just a quarter of patients taking the higher dose of Intercept’s drug. Half of all the patients on that dose also reported itching, which analysts worry may limit the drug commercially because patients won’t be able to tolerate the side effects. Notably, NASH is considered a “silent” disease because its symptoms are mild or go unnoticed until the later stages, at which point patients have significant enough tissue damage that some require liver transplants.
Pruzanski doesn’t agree that NASH is silent. He said these patients often report lower quality of life due to chronic fatigue, abdominal discomfort and the itching that’s common with chronic liver disease. While these reports could be affected by other factors — many NASH patients are overweight or diabetic, for example — for Intercept they affirm a desire for more treatment options among patients and doctors.
Gauging patient interest is just one of the challenges Intercept inherits as a first-mover in NASH. The New York-based company also faces an insurance system expected to be very sensitive about price because of the lofty price tags put on medicines for the last big liver disease, hepatitis C.
“There’s been a lot of fearmongering out there, with this ‘enormous’ population, this ‘tsunami’ of disease,” Pruzanski said, “invoking the days of hep C with Sovaldi and other [direct-acting antiviral] launches.”
“What we’ve set out to do is really reassure payers that while this is a large unmet need,” he added, “we are appropriately focused on this subset of patients with advanced fibrosis.”
Upon launch, Intercept will target the roughly half a million patients who the company expects have advanced fibrosis and are under specialist care. The company has already done more than 100 payer interviews, and internal market research has found 84% of commercial payers see patients with advanced fibrosis patients as the most suitable group to receive its drug.
Yet while Intercept remains bullish on its own prospects, investor confidence in the field cooled last year as Gilead’s lead program disappointed.
“Gilead is sort of the bellwether for liver diseases. And so, to the extent they struggle, it doesn’t bode well for some of the smaller players,” Brian Lian, CEO of NASH drug developer Viking Therapeutics, said in an interview with BioPharma Dive this week.
The year ahead, however, promises several data readouts that could reinvigorate shareholders.
“There was a turnoff in the investment community from these negative studies,” Madrigal CEO Paul Friedman told BioPharma Dive in a recent interview. “I think there’s been a little bit of a swing back of late, but … there’s a lot of variability.”

U.S. to screen passengers for new China coronavirus at three airports

The United States will begin screening at three major airports people coming from central Chinese city of Wuhan for the newly-identified coronavirus that has killed one person and infected at least 40 more in China, public health officials said on Friday.
The Centers for Disease Control and Prevention (CDC) said the screening at San Francisco, New York and Los Angeles airports will begin later on Friday and focus on travelers to the United States via direct or connecting flights from Wuhan.
The risk from the coronavirus to Americans is deemed to be low, the CDC said.
While the U.S. State Department has issued a health alert update about travel to the Wuhan region, the CDC has urged citizens traveling in the region to avoid contact with animals, animal markets or animal products, among other precautions.

Avadim Health sets IPO terms

Avadim Health (AHI) has filed a prospectus for an IPO of 5M common shares at $14 – 16.
The Asheville, NC-based healthcare and wellness company sells topical products aimed at improving immune health, neuromuscular health and skin barrier health targeted to institutional and self-care markets.

Cheap drug may alleviate treatment-resistance in leukemia

A common and inexpensive drug may be used to counteract treatment resistance in patients with acute myeloid leukemia (AML), one of the most common forms of blood cancer. This is the conclusion of a study in mice and human blood cells performed at Karolinska Institutet and SciLifeLab and published in the medical journal EMBO Molecular Medicine. The researchers will now launch a clinical study to test the new combination treatment in patients.
Leukemia is a group of blood cancers that results in excess amounts of white blood cells. There are both chronic forms of leukemia that progress slowly over many years and acute types of leukemia that evolve rapidly. AML affects more than 20,000 people in the United States each year, and the mortality rate is high especially in older patients.
One of the most common drugs to treat AML is cytarabine (ara-C), a cytotoxic drug that interferes with DNA replication. However, many patients do not respond to the treatment because their leukemic cells express high levels of the enzyme SAMHD1, which breaks down the active metabolite of cytarabine, ara-CTP. These patients have a significantly worse survival rate than patients with low leukemic levels of SAMHD1. Therefore, one promising strategy to improve the treatment of AML is to inhibit the effects of this enzyme on cytarabine.
In this study, the researchers tested the impact of more than 33,000 different substances on SAMHD1’s ability to break down ara-CTP in leukemia cells treated with cytarabine. The experiment led to the identification of three different substances, so-called ribonucleotide reductase inhibitors (RNRi), that all reduced SAMHD1’s ability to deactivate ara-CTP: hydroxyurea, gemcitabine and triapine.
“Adding any of these three substances significantly improved the effect of the cytarabine-treatment in cell samples with high levels of SAMHD1,” says Nikolas Herold, researcher at the Department of Women’s and Children’s Health at Karolinska Institutet in Sweden. “This was true for AML samples from both adults and children. In AML-mice, we also saw that the median survival was significantly prolonged when cytarabine was combined with an RNR-inhibitor.”
Hydroxyurea is an inexpensive drug that is used to treat blood diseases such as AML. However, it has not systematically been used in combination with cytarabine. Gemcitabine is a potent drug that is used to treat many different types of cancers, but it can be toxic if given repeatedly. Triapine is a drug currently undergoing clinical studies for cancer treatment. In animal studies, the combination therapies did not exhibit any excess side-effects beyond those already established in cytarabine-treatments.
The research group is now planning to move forward with a clinical study that will evaluate the effect of combining standard AML-treatment with hydroxyurea in recently diagnosed patients. The study will be conducted in collaboration with the Swedish AML-group and will begin recruiting patients within a few weeks.
“Hydroxyurea is an approved drug that is already used to treat AML, so we think it has great potential,” says Nikolas Herold. “If our research results can be confirmed in clinical trials, the treatment of AML could be significantly improved also in developing countries with limited resources since hydroxyurea is patent-free and doesn’t cost more than ibuprofen.”
The researchers were also able to show how the RNR-inhibitors affected the SAMHD1-levels mechanistically. These drugs change the intracellular composition of deoxynucleoside triphosphates (dNTP), which are building blocks for molecules. Since SAMHD1 needs dNTPs to activate its enzymatic activity, this effectively abrogates its ability to break down ara-CTP.

Story Source:
Materials provided by Karolinska InstitutetNote: Content may be edited for style and length.

Journal Reference:
  1. Sean G Rudd, Nikolaos Tsesmetzis, Kumar Sanjiv, Cynthia BJ Paulin, Lakshmi Sandhow, Juliane Kutzner, Ida Hed Myrberg, Sarah S Bunten, Hanna Axelsson, Si Min Zhang, Azita Rasti, Petri Mäkelä, Si’Ana A Coggins, Sijia Tao, Sharda Suman, Rui M Branca, Georgios Mermelekas, Elisée Wiita, Sun Lee, Julian Walfridsson, Raymond F Schinazi, Baek Kim, Janne Lehtiö, Georgios Z Rassidakis, Katja Pokrovskaja Tamm, Ulrika Warpman‐Berglund, Mats Heyman, Dan Grandér, Sören Lehmann, Thomas Lundbäck, Hong Qian, Jan‐Inge Henter, Torsten Schaller, Thomas Helleday, Nikolas Herold. Ribonucleotide reductase inhibitors suppress SAMHD 1 ara‐ CTP ase activity enhancing cytarabine efficacyEMBO Molecular Medicine, 2020; DOI: 10.15252/emmm.201910419