Ban on glyphosate would be ‘disaster’ for Brazil agriculture: minister

A potential ban on the popular herbicide glyphosate in Brazil over concerns it may cause cancer in humans would be a “disaster” for the country’s agricultural industry, Agriculture Minister Blairo Maggi said on Thursday.

A Brazilian court ruled on Aug. 3 that new products containing the chemical could not be registered in the country and existing registrations would be suspended starting from September, until health authority Anvisa issues a decision on its re-evaluation of glyphosate’s safety.

Maggi said that glyphosate is used on around 95 percent of soy, corn and cotton harvested in the country and that there is no readily available substitute. Brazil is the world’s top exporter of soy and a major producer and exporter of corn.

“Glyphosate makes it viable for us to plant and grow crops. What is the alternative?” Maggi said at an event in Rio de Janeiro.

Brazil’s Solicitor General’s office has said it is preparing an appeal to the court decision with the Agriculture Ministry’s backing. Maggi said he is confident the ruling will be overturned on appeal.

The Brazilian court case is part of a global pushback against the chemical. A U.S. judge ruled last week that Monsanto must pay $289 million in damages to a man who alleged its glyphosate-based products like Roundup caused his cancer.

Monsanto, taken over earlier this year by Bayer AG, said in a statement that more than 800 reviews, including those by the U.S. environmental and health authorities, support that glyphosate does not cause cancer. The company is appealing the U.S. court ruling.

Brazil federal prosecutors brought the case to force Anvisa to make a decision in its re-evaluation of glyphosate, which it started in 2008, said Marco Antonio Delfino de Almeida, a member of a prosecutors’ working group on pesticides.

A 2015 assessment by the World Health Organization’s International Agency for Research on Cancer determined glyphosate probably causes cancer in humans, which provides a basis for reconsidering its safety, Almeida said.

If the Brazil ban on existing product registrations goes into effect, it could disrupt farmers who are set to begin planting soy in September.

The sale of glyphosate products would be halted and farmers who use products with suspended registrations could face legal risks, said Brazil-based agribusiness lawyer Frederico Favacho.

Anvisa told Reuters it is prioritizing its re-evaluation of glyphosate but did not give a timeframe for announcing its findings.

https://reut.rs/2MvOnRG

Louisiana seeking comments on ‘Netflix’ model for hepatitis C drugs

As drug costs continue to capture national attention and the Trump Administration tries its hand at providing relief, Louisiana has rolled out a proposal it thinks can help solve the state afford the high cost of hepatitis C drugs.

The state is proposing a “subscription-based payment model” in which it would partner with a hep C drugmaker to pay a fixed annual cost for unlimited access to drugs to treat Medicaid recipients and prisoners. In a request for comments on the proposal, the state notes that the patients are underserved by current payment systems, and that the model could benefit the state and drugmakers alike.

Louisiana Department of Health Secretary Rebekah Gee said in a statement that such a model “would create an incentive for us to find and treat as many people as possible.”

For an industry partner, Gee noted the proposal “would guarantee a fixed purchase price for a contracted period of time, and would allow the drug manufacturer to expand their product reach into populations that otherwise would not have received treatment.”

Louisiana rolled out its request for comments earlier this month and comments are due late next week. Previously, the state explored a plan to request that the federal government break Gilead hep C patents.

At an event in New Orleans last week, HHS Secretary Alex Azar called the subscription idea “interesting,” according to The Advocate. He declined to comment further because no formal proposal has been submitted, the publication reports.

Meanwhile, the National Governor’s Association Center for Best Practices recently named (PDF) the model as a strategy to control pharmaceutical costs while ensuring access. In an op-ed in The Hill, Dana Goldman, part owner of industry consultancy Precision Medicine Group, wrote that the proposal “makes a lot of sense” because manufacturing costs are low for the drugs and the contracts would reward innovation. He likened it to the “Netflix model” for prescription drugs.

A spokesperson for Gilead said the company welcomes Louisiana’s “consideration of a subscription-based model for hepatitis C medicines as an opportunity to increase access for patients that need them.”

“Our commitment to helping make these medicines accessible to those who need them includes exploring innovative approaches that address access gaps in today’s healthcare system,” she added. “We are optimistic that innovative approaches like the proposed subscription-based model will help increase access to curative HCV treatments for people across the state.”

Gilead set off a global debate over drug pricing when it launched hep C med Solvaldi back in 2013 at a price of $84,000 for a 12-week course. At the time, many states said the cost of the drug could deplete their Medicaid budgets. Since then, other hep C drugs have hit the market and prices have fallen dramatically, but the debate over pharma’s pricing has not died down.

A representative for drug industry trade group PhRMA said in an email the organization is reviewing Louisiana’s proposal “with great interest.” She added that PhRMA looks “forward to engaging with policymakers in Louisiana and beyond to ensure affordable access to innovative medicines for patients.”

The proposal comes as the Trump Administration works to implement its drug pricing “blueprint” aimed at increasing competition and negotiation for pharmaceuticals and lowering costs. Meanwhile, many states have taken drug pricing into their own hands after years of gridlock in Washington, D.C.

California, Nevada and Oregon are among states that have passed drug pricing legislation recently. Maryland passed a bill focused on “unconscionable” generic price increases, but the law didn’t stand up to a legal challenge from the generics industry.

All told, state legislators are looking at dozens of bills focused on pharmacy benefit managers, transparency, rebates and more, according to the National Academy for State Health Policy.

https://bit.ly/2MtJwjV

Merck, Eisai announce FDA approval of liver cancer med

Eisai Inc. (ESALY) and Merck (MRK) announced that the U.S. FDA approved the kinase inhibitor LENVIMA for the first-line treatment of patients with unresectable hepatocellular carcinoma. This approval was based on results from REFLECT, where LENVIMA demonstrated a proven treatment effect on overall survival by statistical confirmation of non-inferiority, as well as statistically significant superiority and clinically meaningful improvements in progression-free survival and objective response rate when compared with sorafenib in patients with previously untreated unresectable HCC.

https://bit.ly/2MSqmkQ

Clear benefit with use of automated inpatient alerts–often overridden

• Patients whose doctors use computerized alerts to notify them when their care instructions stray from evidence-based guidelines have fewer complications, shorter hospital stays, lower rates of readmission and lower costs, a new study in The American Journal of Managed Carefinds.
• Researchers at Cedars-Sinai Health System in Los Angeles analyzed 26,424 inpatient visits to see how outcomes and costs varied when doctors did or did not use automated alerts based on the Choosing Wisely guidance. An alert was triggered if, for instance, a doctor ordered a sedative for a sleepless older patient, which could put them at risk of falls.
• When doctors didn’t follow alerts, their patients’ odds of complications rose by 29% and their odds of readmission increased by 14%. Those patients also experienced a 6.2% longer length of stay and 7.3% higher costs — or $944 — after adjusting for severity of illness and case complexity, the study says.

This is the first assessment of the link between adherence to multiple Choosing Wisely guidelines delivered via clinical decision support software and impact on clinical outcomes and cost. Choosing Wisely is an ABIM Foundation campaign that was launched in 2012 to enhance clinical communications between physicians and patients with evidence-supported care.

The researchers point to several limitations in the study, including its strict definition of alert compliance, which excluded visits where doctors followed some but not all of the alerts. In addition, the study doesn’t gauge the impact of specific alerts on costs and outcomes to see if some are more effective than others.

Still, they say the results are statistically and financially significant. “Our findings contribute to the evidence base surrounding the use of CDS and improvements in patient clinical and financial outcomes,” the authors wrote. “Formal prospective cohort studies and randomized CDS intervention trials, perhaps randomizing providers assigned to receive CDS interventions, should be prioritized to help guide future provider strategies in regard to reducing low-value care.”

The study shows that clinical alerts can be a valuable tool in improving patient care, if they are followed regularly. Unfortunately, that’s not always the case. Alert fatigue is a major issue for doctors and hospital support staff, and one that contributes to medical errors. In a national survey, 19 out of 20 hospitals called alert fatigue their chief patient safety concern.

A study by The Doctors Company found that user error, such as data entry mistakes and alert fatigue, played a role in 58% of EHR-related malpractice claims. But the study also cited system failures such as alerts and alarms that failed to sound.

Hospital administrators also need to do a better job of convincing clinicians of the importance of alerts and other CDS tools in clinical care. In a study in the Journal of the American Medical Informatics Association, nearly three-fourths of medication-related clinical decision support alerts in inpatients were overridden — 40% of them inappropriately so.

https://bit.ly/2BgvvSk

Insurance brokers see higher ObamaCare plan premiums, market instability

• A new report by the Center on Health Insurance Reforms at Georgetown University’s Health Policy Institute offered insights from insurance brokers and agents about how federal policy changes are reshaping healthcare coverage.
• One tenet of the Affordable Care Act was to improve access to care and health insurance coverage. However, brokers said healthy, higher-income Americans are being pushed out of the individual health insurance market by rising premiums, turning instead to cheaper policies with limited protections.
• Health insurance brokers expect other health plan options, such as short-term health plans, will gain enrollment, leaving those left in the individual market to shoulder higher premiums.

Published by the Robert Wood Johnson Foundation, the report explored how limited plan choices, narrow networks and rising unsubsidized premiums are affecting the individual market, including the ACA exchanges.

The report warned that unless states protect their ACA exchanges, those plans could face more instability and spiraling costs.

The report focused on six states — Georgia, Iowa, Mississippi, New Hampshire, Texas and Utah. They all have “fragile markets” and higher than average premium increases and loss of insurers, according to the report.

Significant premium increases, fewer plan options and narrow provider networks are leading people to drop ACA plans, especially higher-income and healthier consumers, who aren’t eligible for government subsidies. The ACA provides subsidies for people with individual insurance who are up to 400% of the federal poverty level.

They’re eyeing short-term plans and healthcare sharing ministries instead.

The ACA limited short-term plans only to young adults or people who couldn’t afford other coverage. The law also kept those plans to three months. The Trump administration is making changes to drive short-term plan enrollment, including allowing anyone to get a plan and extending them from three months to one year with the option of renewing them for a total of three years.

These plans are cheaper, but they don’t offer ACA protections. They often don’t provide coverage found in other plans, such as pre-existing conditions, mental health, maternity care and prescription drug benefits.

Brokers said they’ve also moved many people from individual plans to small-group market plans, which have lower premiums and wider networks. Some brokers spoke positively about the potential of association health plans, which the Trump administration sees as a key way to provide cheaper health insurance options.

Brokers also said people are interested in direct primary care arrangements, which are contracts between patients and a primary care provider, and fixed indemnity plans. They said marketing of healthcare sharing ministries and direct primary care arrangements are increasing.

Many healthcare experts are giving similar predictions about the ACA exchanges and individual insurance. The difference in this report is that the insights are coming from brokers. The brokers are working directly with Americans with individual insurance who are struggling with costs and looking for plans they can afford.

The year 2019 could bear out upheavals in the exchanges and individual market. With Congress spiking the individual mandate penalty in 2019 and the Trump administration expanding lower-cost plans with fewer protections, next year will be worth watching.

https://bit.ly/2Pe9qqs

Catalyst gives positive hemophilia update as 2 more subjects complete study

• Two additional subjects completed Catalyst Biosciences’ ongoing hemophilia Phase 2/3 trial without any bleeding or developing any anti-drug antibodies (ADAs), the company said in a statement Wednesday.
• The San Francisco, California-based biopharma initially released interim data in July on the first subject in the study, which aims to enroll 12 total participants. Consistent with the first patient, all three who have completed the trial have yet to exhibit bleeding or develop ADAs. The company also said two more subjects are currently enrolled.
• Catalyst is developing MarzAA, short for Marzeptacog alfa (activated), as a subcutaneous Factor VIIa therapy for treating hemophilia A or B with inhibitors. They presented the new data Wednesday in Boston at the 2018 Hemophilia Drug Development Submit.

In the last few years, hemophilia has turned into one of the most competitive areas among blood disorder therapies. Drugmakers are now seeking not just effective hemophilia treatments, but longer-lasting and safer options.

Currently, Roche AG’s Hemlibra (emicizumab) is the front-runner in that regard, although the Swiss pharma disclosed in March that five patients with hemophilia A died since 2016 while undergoing treatment, though the causes of death were shown to be unrelated to the drug.

But new data from a late-stage program released in May impressed Wall Street, showing Hemlibra as a powerful hemophilia A treatment with or without inhibitors.

Gene therapies are also in development, although they have had their own speed bumps in the path to approval and the market. Spark Therapeutics, for instance, lost $1 billion in market value earlier this month when it released mixed Phase 2 results for its hemophilia gene therapy.

While it’s too early in the study to draw any conclusions on the longevity of Catalyst’s treatment, the initial results from the three subjects who have completed the trial are encouraging.

The study is formatted to take a patient through an individual dose escalation, but only if a breakthrough bleed occurs in the patient. The first stage is 50 days with 30 µg/kg; the second stage is 50 days with 60 µg/kg; the third stage is 50 days with 90 µg/kg; and the final stage is 50 days with 120 µg/kg.

“We have not observed any bleeds or anti-drug antibodies in the two additional subjects, who most recently completed dosing with 30 µg/kg MarzAA, as well as in the previously reported individual who completed 50 days of dosing with 60 µg/kg​ MarzAA,” Catalyst CEO Nassim Usman said in a statement.

Long-acting hemophilia drugs were chosen as BioPharma Dive’s 2017 Disruption of the Year, driven by the fact that the global market is expected to surpass $25 billion by 2024.

https://bit.ly/2MPPkRD

Microbial Activity in the Mouth May Differentiate Children with Autism

New research suggests that shifts in the bacteria within a child’s mouth could provide objective biomarkers for identifying autism spectrum disorder. The findings of this research, conducted by scientists from Penn State Medical Center, SUNY Upstate Medical University, and Quadrant Biosciences Inc. catalyze development of a novel, saliva-based panel to aid clinicians in the early diagnosis of autism spectrum disorder. The new study, “Oral Microbe Activity in Autism,” was published online by the journal Autism Research.

Previous research has suggested that bacteria living in the gastrointestinal (GI) tract may influence autistic behavior. Moreover, autism spectrum disorder (ASD) is associated with several abnormalities related to the mouth and throat, including taste and texture aversions, speech difficulties and salivary transcriptome alterations.

“There is mounting evidence that the GI microbiome is disrupted in children with ASD, and this study shows that this disruption may extend to the mouth and throat. It appears that gene expression activity within oral microbial communities is altered in children with autism spectrum disorder,” said Steven Hicks, MD, Ph.D., of Penn State Hershey, lead investigator on the project. “The shifts in microbial populations were associated with ASD co-morbidities such as GI disturbances, as well as social and repetitive behaviors. This research suggests that measuring activity of these microbial populations in saliva may provide objective biomarkers to aid in the clinical evaluation of ASD.”

In this study, researchers identified changes in the salivary microbiome of 346 children aged 2-6 years across three developmental profiles: ASD (n=180), non-autistic developmental delay (DD) (n=60), and typically developing children (TD) (n=106). Saliva was collected via cheek swab from each study participant. RNA from actively transcribing microbes was sequenced, quantified and analyzed across the three groups of children. ASD children with and without GI disturbances were also compared. The researchers found 12 groups of microbes to be altered between the development status groups and identified 28 groups that distinguished ASD patients with and without GI disturbances. Five ratios of microbes distinguished ASD from TD children (79.5% accuracy), three distinguished ASD from DD (76.5% accuracy), and three distinguished ASD children with/without GI disturbance (85.7% accuracy). Interestingly, the microbial gene expression patterns associated with autism were implicated in energy processing.

“The underlying association of specific microbial population shifts with ASD status will require further study, but may result from alterations of microbial metabolism, or through pathogenic microbial-host relationships,” said Frank Middleton, Ph.D., study co-investigator from SUNY Upstate Medical University. “We saw significant differences in gene expression in these organisms that were associated with lysine degradation, an important building block in neurotransmitter production.”

Richard Uhlig, Founder and Chief Executive Officer ofQuadrant Biosciences and one of the co-authors of the study, noted that Quadrant is developing a saliva-based biomarker panel to aid clinicians in the earlier diagnosis of ASD. “These research findings have been fundamental in our ongoing efforts to develop a biomarker panel that can provide clinicians and parents with more confidence in the diagnosis of ASD. Examining microbial activity will be a crucial element of the panel,” he said. “Our aim is to offer a molecular diagnostic that can provide objective support for the diagnosis of ASD as early as possible, when treatment is most efficacious.”

https://bit.ly/2w8R15S