U.S. government experts, industry spar over asbestos testing in talc

For the first time in nearly 50 years, the U.S. Food and Drug Administration examined asbestos testing for talc powders and cosmetics at a hearing on Tuesday, after traces of the known carcinogen were found in several such products, including Johnson & Johnson’s Baby Powder.
Citing those FDA findings, some U.S. lawmakers and consumer advocates have called for stricter safety regulations to protect public health.
J&J, the market leader in talc powders, has defended the safety of its talc. The company said tests by labs it hired found no asbestos in samples from the same bottle the FDA examined – except for some the company attributed to contamination from a laboratory air conditioner.
In a statement on Tuesday, the company said it looks forward to the FDA’s “thorough review of the most effective and reliable ways to test for asbestos in cosmetic talc.”
The hearing on asbestos testing in talc, the FDA’s first since 1971, focused on testing standards recommended by a panel of government experts. The recommendations, published last month, embrace positions held by public health authorities and experts for plaintiffs who in lawsuits allege that contaminated talc products caused their cancers.
An industry trade group criticized the recommendations, saying they would not improve product safety.
For decades, the cosmetic talc industry has largely been allowed to police itself with little FDA oversight. Although talc and asbestos are similar minerals often found together in the ground, the FDA has never required manufacturers to test for the carcinogen.
One of the most significant recommendations from the expert panel is that mineral particles found in talc products small enough to be drawn into the lungs, even those the industry would not technically categorize as asbestos, should be counted as potentially harmful.
In its report, the panel said both asbestos and look-alike minerals are suspected of causing “similar pathological outcomes,” so the “distinction is irrelevant.”
At Tuesday’s hearing, a government toxicologist said a wide range of spear-shaped mineral particles – including but not limited to asbestos – can trigger the development of cancer and should be part of any new testing regime.

‘THIS IS UNACCEPTABLE’

Christopher Weis, a senior advisor with the National Institute of Environmental Health Sciences, said research has shown that conventional testing methods have failed to detect the full range of hazardous fibers, known as elongated mineral particles, or EMPs.
The process of milling talc for powders and cosmetics is known to break down any contaminants into small EMPs.
“All EMPs have the ability to trigger” development of cancer and other diseases, Weis said at the FDA hearing. “Short EMPs are not conventionally counted or included in lab reports. As a toxicologist, this is unacceptable.”
Mark Pollak, chief operating officer for the Personal Care Products Council, said the recommendation for counting more mineral particles as potentially harmful is not supported by science. The cosmetics trade group represents about 600 companies.
“Counting all (elongated mineral particles) would provide misleading reports, suggesting the presence of asbestos when none exists,” Pollak said at the hearing. “The key to effective testing is identification of asbestos, not harmless minerals.”
Scott Faber, senior vice president for government affairs at the Environmental Working Group, urged the FDA to endorse the more rigorous testing methods and said the agency should add a warning label to talc products so consumers are aware they may contain asbestos.
“It’s time to end the honor system which has failed consumers for so long,” Faber said at the hearing. “Let’s not wait another 50 years to finally protect consumers.”
The U.S. Occupational Health and Safety Administration and the Environmental Protection Agency have limited exposure to asbestos on the job and in the air to reduce cancers since the 1970s, when the hazard was well established. A Reuters report in December (here) showed that, during the same period, the FDA downplayed health concerns, including possible asbestos contamination, in talc powders and cosmetics and repeatedly deferred manufacturers.
Dr. Linda Katz, director of FDA’s office of cosmetics and colors, said the panel of government experts from FDA and other agencies will continue studying these issues and plans to publish a white paper at some point. The FDA has not announced a timetable for deciding whether it will pursue new rules on testing.
The increased scrutiny on this issue follows a 2018 Reuters report (here) which showed that although J&J knew for decades its raw talc and powders sometimes tested positive for asbestos, the company did not report those findings to the FDA.
https://www.reuters.com/article/us-health-fda-talc/u-s-government-experts-industry-spar-over-asbestos-testing-in-talc-idUSKBN1ZY0IX

Earnings before Wednesday’s open

BSX,  HUM, MRK
https://seekingalpha.com/news/3537970-notable-earnings-wednesdays-open

In 7 years, nurse practitioner ranks more than doubled: Problem for hospitals?

The number of nurse practitioners (NPs) in the U.S. more than doubled in just seven years—an unprecedented rate of growth for a major profession, according to a new Health Affairs study.
The number of nurse practitioners grew from about 91,000 to 190,000 from 2010 to 2017, according to the study.

While those nurse practitioners have helped fill critical gaps in healthcare delivery nationwide, it’s created a potential problem for hospitals. Most nurse practitioners practice as registered nurses (RNs) before completing their education to become an NP.

The growth in NPs has reduced the size of the RN workforce by up to 80,000 RNs nationwide, the study authors said, at the same time the more than one million baby-boom RNs are well on their way to retirement.
The authors concluded that hospitals must devise creative strategies to replace those RNs who left their jobs to become NPs and who earned an average salary of just under $95,000 in 2017.

“One implication that has been relatively unexplored in the literature, but that is a frequent topic among hospital chief nursing executives, has to do with the fact that new RN graduates seem to be increasingly leaving hospital positions after only one or two years,” the authors wrote. During their time working at hospitals, they acquire clinical experience and then go on to begin a master’s degree or a doctor of nursing practice program.
The growth in NPs was driven by the rapid expansion of education programs that have attracted Millennial nurses. The number of programs to educate NPs grew from 356 in 2010 to 467 in 2017. Collectively, they now graduate nearly as many new NPs as medical schools do physicians each year, the study said.

Employment for NPs grew the fastest in outpatient care clinics, where growth in earnings was also highest.
The study, which used data from the Census Bureau’s American Community Survey for the period 2010–2017, found the following:

• Employment for NPs was concentrated in hospitals, physician offices and outpatient care centers.
• Growth occurred in every region of the country but was particularly rapid in the east south-central region of the country, which includes Alabama, Kentucky, Mississippi and Tennessee.
• The growth of NPs was accompanied by a modest 5.5% aggregate real earnings growth from 2010 to 2017.
• More care will be provided by nurse practitioners as there are projected to be two NPs for every five physicians in 2030, compared to less than one NP per five physicians in 2016.
• Overall growth in the numbers of NPs has been particularly rapid in outpatient clinics, a growing locus of healthcare delivery.

Concerns about physician shortages have encouraged the greater use of NPs to provide primary care and fill gaps in rural areas.
In addition to the growing number of nurse practitioners, the physician assistant workforce is also one of the fastest-growing professions in healthcare—with an increase in both numbers and salaries.
The number of certified PAs grew over 6% in 2018 and the average salary increased by more than 12% in a four-year span, according to a just-released report from the National Commission on Certification of Physician Assistants.
https://www.fiercehealthcare.com/practices/just-7-years-number-nurse-practitioners-more-than-doubled-why-s-a-problem-for-hospitals

Takeda Shire integration profit surprise —but no U.S. Natpara supply until 2021

Takeda had expected to report an operating loss this fiscal year. But thanks to faster integration with Shire, it’s now looking at a possible profit.
Don’t expect any contribution from Natpara in the U.S., though, Takeda’s chief financial officer said. The rare disease med, recalled in September, won’t be available in the States until March 2021 at the earliest.
The Japanese pharma now expects to report operating profit of 10 billion yen ($92 million) for the fiscal year ending in March versus its previous forecast of a loss of 110 billion yen, the company said. It’s also dialing up its core operating profit guidance by 2.2% to 950 billion yen.

Strong performance from 14 key global drug products and faster cost savings from the Shire takeover contributed to the sunnier outlook, Takeda CFO Costa Saroukos told investors during a call Tuesday. “We have also completed the purchase price allocation for the Shire acquisition, resulting in a positive impact to the reported P&L,” he said.
But not all unexpected developments were positive for Takeda. The company has not recorded any U.S. sales of hypoparathyroidism drug Natpara in the U.S. since a recall launched in September, and, according to Saroukos, it may not be able to for at least another year.
The recall was caused by the risk of rubber particles from the cartridge entering the drug solution. As Takeda works to remedy the problem, it has launched a special use program that provides the med to at-risk patients for free, Saroukos said.
But rather than the usual protocol that allows 14 injections for each cartridge, those patients are advised to only use it once. That means a supply that typically lasts a year would be used up in just one month.

Takeda has said it’s working closely with the FDA to resume supply. “However, based on recent discussions, we expect a delay,” Saroukos told investors. “As a result, we no longer expect to record any U.S. Natpara revenue in fiscal year 2020.”
That means there will be no normal Natpara supply in the U.S. for at least another year, before March 2021. Approved by the FDA in early 2015, Natpara racked up JPY 7.1 billion in U.S. sales in Takeda’s first quarter.
No thanks to that Natpara void, Takeda’s rare disease franchise continues to suffer, with underlying revenues down 11% year over year for the nine months ended in December. But the main drag came from the hemophilia business it inherited from Shire and its hereditary angioedema (HAE) portfolio.
Sales of hemophilia A drug Advate dropped 26% in Takeda’s third quarter ended in December to JPY 39.9 billion ($370 million), probably thanks to competitive pressure from Roche’s Hemlibra. While newly launched HAE drug Takhzyro delivered JPY 18.2 billion sales during the three months, its predecessor Firazyr, which has gone generic, only snagged JPY 7.5 billion, down nearly 70%.

At least one blockbuster grew; sales from inflammatory bowel disease drug Entyvio leapt 38% at constant currencies, reaching JPY 95.1 billion in Takeda’s third quarter. However, Takeda’s plan to introduce a more convenient subcutaneous version of the drug recently hit a setback in the form of an FDA complete response letter.
Takeda is still working with the FDA to resolve that problem, Saroukos said, and expects to update investors by June. Without giving out any further details, Saroukos said the rejection is not related to the drug’s safety or efficacy data.
A top priority at Takeda for the years to come is to pare down the huge mountain of debt it picked up for the $59 billion Shire buyout. To do that, it’s focused on driving growth from 14 key drugs and selling assets outside its five core therapeutic areas.
As of December, Takeda’s net debt/EBITDA ratio has come to 4.1x versus 4.7x at the end of March, though it’s slightly up from 3.9x in September. Saroukos said that was expected as the company has paid the full-year dividend and tax on proceeds on the selloff of Xiidra to Novartis.
https://www.fiercepharma.com/pharma-asia/takeda-expects-surprise-profit-thanks-to-shire-integration-but-no-natpara-u-s-supply

Lonza keeps Chinese plants on ‘holiday’ as coronavirus builds momentum

Swiss CDMO Lonza is extending the Chinese New Year break at its four plants in China, but not to celebrate. The unplanned extension is a precaution as coronavirus continues to spread rapidly through the country.

The company is also imposing restrictions on travel to, from and within the country and requiring a two-week in-home quarantine on employees traveling from China to make sure there is no spread of the virus.

“As a responsible employer, we have taken measures to protect our employees and any third parties visiting our sites in China,” Lonza said.

Lonza said today it has halted operations at a drug formulation and pyromellitic dianhydride production plant in Nanjing, Jiangsu; a plant in Nansha, Guangdong that makes small molecule APIs and niacin; a plant in Suzhou, Jiangsu that makes drug capsules and microbial control solutions; and its biologics plant Guangzhou, Guangdong that is under construction so not operational.

It has no production facilities in the Hubei Province where the outbreak was first discovered, it said but is taking the steps as a precaution. It said most of the plants have decided to extend the holiday into this week as authorities monitor the outbreak.

The extended closure so far has resulted in only limited disruption of supplies, the CDMO said, but it is “assessing the impact” of potential delays to raw materials and finished products as the outbreak’s effects continue.

Lonza’s announcement follows that of Chinese CDMO WuXi Biologics which last week assured clients and the public that the spread of the virus would not affect its drug production schedule. As of a week ago, it said it is “working vigilantly to execute our Business Continuity Plan to mitigate any potential risk” and to ensure its products are unaffected by the outbreak.

Big Pharma players like Pfizer and Roche say they are not exclusively dependent on any supplies from China but there are some areas of concern for U.S. patients. China manufactures an estimated 97% of the country’s antibiotics and many of the APIs used by drugmakers. While no serious supply issues have surfaced, the virus continues to spread and seems to be picking up momentum according to Chinese statistics.

The China National Health Commission reported that through yesterday, confirmed cases have grown more than 3,000 to 20,438 and that there were another 64 deaths, bringing the fatality number to 425.

The infections also are growing globally as countries take measures to try to shield themselves. The U.S., Australia, Singapore, New Zealand and Vietnam are not allowing non-residents who have been to China recently to enter their countries. The U.S. has seen nearly a dozen confirmed cases and reported its first person-to-person transmission inside the country.

https://www.fiercepharma.com/manufacturing/lonza-keeps-chinese-plants-furlough-as-coronavirus-builds-momentum

FDA OKs emergency use of coronavirus test

The FDA has signed off on the emergency use of a molecular diagnostic test developed at the Centers for Disease Control and Prevention (CDC) for 2019-nCoV, the coronavirus causing the current outbreak.

The test, previously limited to use at CDC laboratories, can now be used at any CDC-qualified labs across the U.S.

Related tickers: XLV, CODX, DGX, LH

https://seekingalpha.com/news/3538280-fda-oks-emergency-use-of-coronavirus-test

International Team Develops Promising Broad-Spectrum Antiviral Compound

Drugs to fight viruses, known as antivirals, are relatively recent inventions, with the first approved being in 1982. Since then, numerous others have hit the market, typically to treat HIV, hepatitis, herpes and others. They generally work by inhibiting virus growth, although viruses often mutate and become resistant to these drugs.
An international team of researchers led by the University of Manchester has developed a new antiviral using natural glucose derivatives called cyclodextrins, a type of sugar, which shows promise in treating a broad range of viruses, including herpes simplex, respiratory syncytial virus, hepatitis C, HIV, and Zika virus.
The researchers were from The University of Manchester, the University of Geneva (UNIGE), and the EPFL in Lausanne, Switzerland. The modified sugar molecules were capable of disrupting the outer shell of the virus, destroying them on contact. This approach appears to be effective against drug resistant viruses as well. Their research was published in the journal Science Advances.
“We have successfully engineered a new molecule, which is a modified sugar that shows broad-spectrum antiviral properties,” said Samuel Jones, from The University of Manchester, who co-led the research with Valeria Cagno from the University of Geneva.
Jones went on to say, “We have successfully engineered a new molecule, which is a modified sugar that shows broad-spectrum antiviral properties. The antiviral mechanism is virucidal meaning that viruses struggle to develop resistance. As this is a new type of antiviral and one of the first to ever show broad-spectrum efficacy, it has the potential to be a game changer in treating viral infections.”
They have patented the molecule and a spinout biotech company is being launched to develop it for commercial use. The researchers believe it has the potential to be used in creams, ointments and nasal sprays, although that will require significant time and development.
The investigators wrote, “A drug with an irreversible action, i.e., a virucidal drug, could be ideal to fight viral infection, given that it would not be subject to loss of efficacy upon dilution and have long-lasting effects. All previously identified virucidal molecules have toxic side effects that render their clinical use impossible.”
Cyclodextrins are naturally occurring glucose derivatives. They are used in many commercial applications, including drug delivery, air fresheners, cosmetics and food. Sulfonated cyclodextrins have shown antiviral activity against HIV only and were reversible and virus specific. Highly sulfonated gold nanoparticles have shown broad-spectrum virucidal properties. However, gold nanoparticiles are problematic as drugs because of unknown clearance mechanisms and potential long-term toxicity.
The researchers attached highly sulfonated chemicals to a U.S. Food and Drug Administration (FDA)-approved cyclodextrin scaffold, which resulted in a highly efficient virucidal broad-spectrum molecule that was effective in the lab and in animal models. It showed broad-spectrum activity against a wide variety of viruses from different families of viruses.
“We developed a powerful molecule able to work against very different viruses, therefore, we think this could be game changing also for emerging infections,” said Fancesco Tapparel, one of the senior authors, a researcher with EPFL.
https://www.biospace.com/article/antiviral-made-from-sugar-shows-promise/