Regenerative bandage accelerates healing in diabetic wounds

The regenerative bandage promotes cell spreading and proliferation. The green spots are live cells entrapped in the hydrogel and stained with Calcein-AM. Credit: Ameer Research Lab, Northwestern University

A simple scrape or sore might not cause alarm for most people. But for diabetic patients, an untreated scratch can turn into an open wound that could potentially lead to a limb amputation or even death.

A Northwestern University team has developed a new device, called a regenerative bandage, that quickly heals these painful, hard-to-treat sores without using drugs. During head-to-head tests, Northwestern’s bandage healed diabetic wounds 33 percent faster than one of the most popular bandages currently on the market.

“The novelty is that we identified a segment of a protein in skin that is important to wound healing, made the segment and incorporated it into an antioxidant molecule that self-aggregates at body temperature to create a scaffold that facilitates the body’s ability to regenerate tissue at the wound site,” said Northwestern’s Guillermo Ameer, who led the study. “With this newer approach, we’re not releasing drugs or outside factors to accelerate healing. And it works very well.”

Because the bandage leverages the body’s own healing power without releasing drugs or biologics, it faces fewer regulatory hurdles. This means patients could see it on the market much sooner.

The research was published today, June 11, in the Proceedings of the National Academy of Sciences. Although Ameer’s laboratory is specifically interested in diabetes applications, the bandage can be used to heal all types of open wounds.

The bandage accelerates tissue regeneration in vivo. A stained section of tissue who’s complete resorption of the hydrogel in all four groups of post-wounding. Credit: Ameer Research Lab, Northwestern University

An expert in biomaterials and regenerative engineering, Ameer is the Daniel Hale Williams Professor of Biomedical Engineering in the McCormick School of Engineering, professor of surgery in the Feinberg School of Medicine and director of Northwestern’s new Center for Advanced Regenerative Engineering (CARE).

The difference between a sore in a physically healthy person versus a diabetic patient? Diabetes can cause nerve damage that leads to numbness in the extremities. People with diabetes, therefore, might experience something as simple as a blister or small scratch that goes unnoticed and untreated because they cannot feel it to know it’s there. As high glucose levels also thicken capillary walls, blood circulation slows, making it more difficult for these wounds to heal. It’s a perfect storm for a small nick to become a limb-threatening—or life-threatening—wound.

The secret behind Ameer’s regenerative bandage is laminin, a protein found in most of the body’s tissues including the skin. Laminin sends signals to cells, encouraging them to differentiate, migrate and adhere to one another. Ameer’s team identified a segment of laminin—12 amino acids in length—called A5G81 that is critical for the wound-healing process.

“This particular sequence caught our eye because it activates cellular receptors to get cells to adhere, migrate and proliferate,” Ameer said. “Then we cut up the sequence to find the minimum size that we needed for it to work.”

By using such a small fragment of laminin rather than the entire protein, it can be easily synthesized in the laboratory—making it more reproducible while keeping manufacturing costs low. Ameer’s team incorporated A5G81 into an antioxidant hydrogel bandage that it previously developed in the laboratory.

Immunofluorescence staining of the wound demonstrates enhanced expression of keratin-10, a protein found in the skin. Credit: Ameer Research Lab, Northwestern University

The bandage’s antioxidant nature counters inflammation. And the hydrogel is thermally responsive: It is a liquid when applied to the wound bed, then rapidly solidifies into a gel when exposed to body temperature. This phase change allows it to conform to the exact shape of the wound—a property that helped it out-perform other bandages on the market.

“Wounds have irregular shapes and depths. Our liquid can fill any shape and then stay in place,” Ameer said. “Other bandages are mostly based on collagen films or sponges that can move around and shift away from the wound site.”

Patients also must change bandages often, which can rip off the healing tissue and re-injure the site. Ameer’s bandage, however, can be rinsed off with cool saline, so the regenerating tissue remains undisturbed.

Not only will the lack of drugs or biologics make the bandage move to market faster, it also increases the bandage’s safety. So far, Ameer’s team has not noticed any adverse side effects in animal models. This is a stark difference from another product on the market, which contains a growth factor linked to cancer.

“It is not acceptable for patients who are trying to heal an open sore to have to deal with an increased risk of cancer,” Ameer said.

Next, Ameer’s team will continue to investigate the bandage in a larger pre-clinical model.

 Explore further: Regenerative bandage heals diabetic wounds faster

More information: Yunxiao Zhu el al., “Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes,” PNAS (2018). www.pnas.org/cgi/doi/10.1073/pnas.1804262115

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Endo in Master Settlement of Testosterone Therapy Liability Claims

Endo International plc (NASDAQ: ENDP) today announced that its subsidiaries Endo Pharmaceuticals Inc. and Auxilium Pharmaceuticals, LLC (collectively, “Endo” or the “Company”) have executed a definitive master settlement agreement (the “Agreement”) allowing for the resolution of all known testosterone replacement therapy product liability claims against the Company.  Under the Agreement, provided certain customary conditions are met, Endo will make a one-time deposit into a qualified settlement fund and participating claimants will release their claims.  The Agreement does not increase Endo’s product liability reserve because an accrual was recorded for the settlement, together with other matters, during the fourth quarter of 2017 in connection with a previously announced memorandum of understanding.  The Agreement does not involve any admission of wrongdoing or liability by Endo.

In addition, Endo announced the entry of a significant case management order by the Hon. Matthew F. Kennelly, U.S. District Judge, U.S. District Court for the Northern District of Illinois, in MDL No. 2545 (In Re Testosterone Replacement Therapy Products Liability Litigation).  The order requires, among other things, that any future claimants and existing claimants electing not to participate in the settlement produce certain information within specified timeframes.  The order further allows for expedited discovery on claimants and dispositive motion practice on certain defenses, and permits only limited discovery on Endo.

“We are very pleased with today’s announcement.  We believe the master settlement agreement allowing for resolution of all known testosterone replacement therapy product liability claims against Endo marks another important achievement for the Company to deliver on its multiyear turnaround strategy,” said Matthew J. Maletta, Endo’s Executive Vice President and Chief Legal Officer. “We expect the master settlement agreement and case management order will collectively assist claimants to move forward with their lives and permit Endo to move forward with an even greater focus on its core business priorities,” he added.

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Wide spectrum of patients see better outcomes at academic medical centers

• Medicare patients who received treatment at an academic medical center (AMC) had lower 30-day mortality rates compared to those at nonteaching hospitals, according to a recent Health Affairs study. This was the case not just for the sickest, but also among less sick patients.
• After adjusting for patient and hospital characteristics, the study found high-severity patients had 7% lower odds of 30-day mortality, medium-severity patients had 13% lower odds and low-severity patients had 17% lower odds compared to similar patients at nonteaching facilities. For surgical procedures, high-severity patients had 17% lower odds of mortality, medium-severity patients had 10% lower odds and low-severity patients saw no difference.
• “Taken together, these findings suggest that efforts to limit care at academic medical centers have the potential to lead to worse outcomes, as mortality rates for even low-severity patients seem to be lower at the centers,” the study authors wrote.

AMCs are often seen as a better alternative for patients with complex conditions.

However, some payers exclude those facilities from narrow networks because they have higher costs. The study, funded by the Association of American Medical Colleges, looked at 11.8 million hospitalizations between 2012 and 2014 in nearly 4,500 hospitals, most of which were nonteaching facilities.

Academic centers are thought of as places to care for the sickest patients because of their breadth of expertise, technology and innovative programs. But, because of the high spending, they haven’t been seen as the best option for those needing less intense care. The Health Affairs report, however, shows that AMCs can improve outcomes for patients who are not the sickest.

The authors acknowledged being somewhat surprised about the association between status and mortality being as strong or stronger among low- and medium-severity patients compared to high-severity patients with common medical conditions. They said the result could be because healthier patients get the benefit of the AMC’s abilities if there are complications, or that AMCs have lower rates of diagnostic errors for some conditions, which improves outcomes.

Given the higher costs of AMCs, the study authors said figuring out which patient groups would benefit from receiving care at a teaching facility is “an important step toward a higher-value care system.” They suggested that stratifying by risk will likely not be worthwhile. “To the extent that policymakers or clinical leaders want to steer patients away from teaching hospitals, they will need a different approach to identify which patients don’t benefit from that care,” they wrote.

AMCs face a challenging world of higher expenses, payers nudging patients to lower-cost facilities, lower Medicare and Medicaid reimbursements and reduced government funding for research. That’s pushing some to look at M&As and partnerships with nonacademic providers to survive. A 2017 JAMA report suggested that AMCs that merge with nonacademic providers may put their research missions at risk

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Fixing healthcare provider directories a low-risk way to test blockchain?

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• A new white paper from EY Advisory and Humana highlights how distributed ledger technologies, including blockchain, can improve the quality of provider data while reducing costs and duplicative efforts.
• The report suggests that improving routine administrative activities, such as provider data management, is one way to reduce inefficiency and waste in the healthcare industry.
• A crowdsourced provider data marketplace could enable payers and third-party data sources to improve provider data quality, which is often riddled with outdated information, according to the report.

U.S. healthcare organizations spend $2.1 billion each year to maintain provider data and 75% of it is duplicative. That’s partly because payers and other industry stakeholders can’t maintain high-quality data in a heavily siloed industry, according to the report.

Blockchain offers the chance to collaborate on a program to release data stuck in silos.

Using provider directories is also one low-risk way to test out blockchain. Provider directories are often wrong. CMS has said 52% of Medicare Advantage online provider directories are incorrect and the agency is hoping greater oversight will improve the situation.

That won’t improve payer network provider information for commercial plans, though. Payers maintain individual provider data for their in-network providers, which duplicates efforts and opens up a higher chance for mistakes. However, the white paper said payers are increasingly working together to collaborate on increased efficiencies for PDM services. That includes increasing the provider directory quality.

Going with a crowdsourced provider data marketplace will “more efficiently distribute the effort and cost” and reduce duplicative efforts, according to the paper. Blockchain technologies, including distributed ledgers and smart contracts, allows for data exchanges and connect multiple healthcare stakeholders. That has the chance to “address current friction points” as well as reduce inefficiencies and improve standards.

“Marketplaces have disrupted status quo and delivered value and efficiencies to customers in every industry, including healthcare. We now have the technical capabilities to apply a marketplace model to PDM,” according to the report.

By starting with provider data maintenance, healthcare could test blockchain and lead to a technical foundation to share other types of more sensitive data.

Humana is already working with MultiPlan, UnitedHealth Group’s Optum, UnitedHealthcare and Quest Diagnostics on a pilot blockchain project to fix provider network lists. That project looks to figure out how payers’ provider directories can offer the latest information.

Humana and UnitedHealth aren’t the only payers that see blockchain’s potential. A 2017 Black Book Market Research survey found three-fourths of payer executives are either thinking of deploying or in the process of implementing blockchain technology.  Also, 29% of hospital executives and 82% of payers claimed a working knowledge of blockchain in the 2017 third quarter.

Many of these officials also see blockchain’s potential for improved interoperability. The survey found that at least nine out of 10 people surveyed among payers, medical group managers and IT specialists see the promise of blockchain. More than two-thirds of hospital officials (70%) also see the potential of how blockchain could address connectivity issues and data sharing, according to Black Book.

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Investors ready to resuscitate Johnson & Johnson’s ailing stock

Johnson & Johnson (JNJ.N) shareholders have endured a painful year amid worries about prospects for its many businesses, but investors capitalizing on the stock’s relatively cheap valuation may be set to apply a Band-Aid to the declines.

Shares of J&J, the largest U.S. healthcare company by market value, had slumped 11.2 percent this year as of Friday’s close, although recent gains may indicate the start of a rebound. The stock’s year-to-date decline compares to more than 2 percent gains for both the S&P 500 healthcare sector .SPXHC and the blue chip Dow Jones Industrial Average .DJI, of which J&J is a member.

If J&J ends the year with its current 11.2 percent decline, 2018 will be the worst calendar-year performance in 25 years for the stock, a bellwether for the healthcare sector and one traditionally considered a safe-haven investment during periods of market uncertainty.

The diversified company, whose products include Band-Aid bandages, Tylenol pain reliever, replacement knees and cancer and immunology medicines, faces concerns in all three of its main segments – pharmaceuticals, medical devices and consumer.

But the stock’s swoon makes it look particularly cheap, based on its price-to-earnings ratio of 14.8 times forward earnings estimates, which is enticing investors, along with the stock’s above-market dividend yield of 2.9 percent.

“We are much more upbeat about J&J today than we were six months ago,” said David Katz, chief investment officer at Matrix Asset Advisors in New York, as the stock traded just above $120 a share.

“We definitely think it’s an attractive investment opportunity,” Katz said.

J&J shares are up more than 3 percent in June, following five straight months of declines, the stock’s longest such losing streak in over a decade.

J&J’s pharmaceuticals segment, roughly half of company revenue, saw sales jump by 19 percent in the first quarter. But concerns about generic-drug competition eroding sales of prostate cancer medicine Zytiga, a standout in the first quarter, and rheumatoid arthritis drug Remicade have investors leery about the segment’s future performance.

Pharmaceuticals has been the strongest segment of J&J’s businesses, but “the ability to sustain an above-average growth rate has been a question,” said Dean Dillard, senior research analyst at USAA Investments in San Antonio.

J&J’s medical devices segment including its orthopedics business has been losing market share, said Jeff Jonas, a portfolio manager focusing on healthcare for Gabelli & Co.

Performance in J&J’s consumer segment has been “pretty lackluster for a few quarters,” Jonas said. The division also may be subject to weak investor sentiment in general for consumer brand companies, amid fierce competition and other concerns.

“There is concern around all three of the businesses,” Jonas said.

J&J shares may also be suffering from concerns about scrutiny over prescription drug costs that are undermining pharmaceutical shares broadly.

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“Sentiment remains fairly negative for the group, so that by and large does not help Johnson & Johnson,” said Kevin Gade, a portfolio analyst, who follows pharmaceutical stocks at Bahl & Gaynor Investment Counsel in Cincinnati.

VALUATION ATTRACTIVE

The stock’s recent valuation at 14.8 times earnings estimates for the next 12 months is its lowest since late 2015 and well below its five-year average of 16.5 times, according to Thomson Reuters Datastream.

J&J is also trading at a nearly 10 percent discount to the S&P 500 .SPX, compared to the slight premium it has held over the benchmark index on average over the past five years.

Also appealing, investors said, is J&J’s dividend yield of 2.9 percent compared to 1.9 percent for the S&P 500, as well as the company’s track record of consistently raising it.

Aside from paying its dividend, some investors want J&J to use its cash for a stock buyback or for an acquisition to improve its growth prospects.

J&J is “capable of doing 10 $5 billion transactions. We don’t have to do a $50 billion transaction,” Chief Financial Officer Dominic Caruso told an investor conference last week.

J&J’s broad healthcare portfolio, which offers products that people will require even in economic down times, helps position it as a safe-haven stock in the event of market volatility or an increasingly uncertain economy.

“If and when the economy sees negative growth,” Gade said, “relative to the market, Johnson & Johnson is the type of company and business model an investor would want to hold.”

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Eagle Gains 7 Year Orphan Drug Exclusivity for Leukemia/Lymphoma Med

 Eagle Pharmaceuticals, Inc. (Nasdaq:EGRX) (“Eagle” or the “Company”) announced today that the U.S. District Court for the District of Columbia (the Court) has issued a decision requiring the FDA to grant seven years of orphan drug exclusivity (ODE) in the U.S., for BENDEKA™ (bendamustine hydrochloride injection, or bendamustine HCI), a liquid, low-volume (50 mL) and short-time 10-minute infusion formulation of bendamustine hydrochloride.

As a result of the Court’s decision, the FDA will not be able to approve any drug applications referencing BENDEKA until the ODE expires in December 2022. Moreover, the Company now does not expect generic TREANDA^® entrants into the market until 2022, rather than November 2019.

“We are delighted with the court’s decision to grant orphan drug exclusivity for BENDEKA, further extending the longevity of this important product,” said Scott Tarriff, Chief Executive Officer. “With thirteen Orange Book listed patents extending from 2026 through 2033, and additional pending patent applications, the market protection for BENDEKA is likely to be intact for many years. We also believe it will provide for continued profitability and building long-term value for Eagle,” concluded Tariff.

Orphan drug exclusivity is granted by the FDA Office of Orphan Products Development to drugs or biologics that treat rare diseases or conditions affecting fewer than 200,000 patients in the U.S. The designation typically provides the drug developer with a seven-year period of U.S. marketing exclusivity upon approval, bars FDA from approving any other application (ANDA, 505(b)(2) or “full” NDA or BLA) for the same drug for the same orphan disease, and offers certain financial incentives that can help support its development.

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LabCorp Expands Drug Development Solutions with Acquisition of Sciformix

 LabCorp® (NYSE: LH), a leading global life sciences company, announced today that it has acquired Sciformix Corporation, a scientific process outsourcing company focused on pharmacovigilance and regulatory solutions for biopharmaceutical and medical devices clients. Sciformix will become part of Covance, LabCorp’s drug development business.

“This acquisition strengthens our position in the later phases of drug and device development, particularly for post-marketing pharmacovigilance and market access solutions,” said David P. King, chairman and chief executive officer of LabCorp. “The addition of Sciformix’s scientific and technology expertise, combined with its quality-driven processes, will support Covance’s work in transforming drug development through innovation and greater efficiency.”

Sciformix’s offerings include post-marketing safety and risk management, clinical development support services, regulatory affairs and operations, technology services, and real-world evidence solutions. The majority of Sciformix’s 1,100 employees are based in Asia, accelerating Covance’s global expansion.

“The development process does not end once a drug or device is approved,” said Bill Hanlon, Ph.D., group president of Clinical Development and Commercialization Services at Covance. “More than ever, approved treatments must be monitored closely to demonstrate a continued favorable benefit-risk ratio in a much broader population and to safeguard patient safety. Pharmacovigilance solutions address that need. Sciformix’s services and expertise are a compelling addition to Covance’s portfolio. With its scientific knowledge and high-quality delivery, Sciformix is a great fit with our culture and our mission to improve health and improve lives.”

Manish Soman, former president and chief executive officer of Sciformix, said: “Our complementary offerings add depth and breadth to each company’s capabilities, creating an exciting opportunity to offer customers an enhanced range of comprehensive services by a single company.” Ajit Nagral, Sciformix founder and former executive chairman, added: “Sciformix is delighted to become part of the Covance and LabCorp family, bringing new opportunities for our employees as they work to improve healthcare for patients worldwide.”

Terms of the transaction have not been disclosed.

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