Cardinal Health : Drug supply firm execs say they didn’t cause opioids crisis

Top executives of the nation’s leading wholesale drug distributors told Congress under oath Tuesday that their companies didn’t help cause the nation’s deadly opioid epidemic, drawing bipartisan wrath that included one lawmaker suggesting prison terms for some company officials.

The confrontation came at a House subcommittee hearing at which legislators asked why huge numbers of potentially addictive prescription opioid pills had been shipped to West Virginia, among the states hardest hit by the drug crisis. Lawmakers are making an election-year push for legislation aimed at curbing a growing epidemic that saw nearly 64,000 people die last year from drug overdoses, two-thirds from opioids.

Company officials’ responses ranged from apologies to explanations to finger-pointing at doctors who prescribe the drugs, pharmacies that fill prescriptions and the federal Drug Enforcement Administration for not doing enough as overseer of sales of legally controlled substances.

In a scene that recalled Congress’ 1994 grilling of tobacco industry officials, House Energy and Commerce investigations subcommittee Chairman Gregg Harper, R-Miss., administered oaths to the heads of five pharmaceutical distributors and asked each if “the actions you or your company took contributed to the opioid epidemic.”

Answering no were the leaders of the nation’s three biggest distribution firms: McKesson Corp., Cardinal Health Inc. and AmerisourceBergen Corp., which dominate the U.S. market. The only yes came from Joseph Mastandrea, chief of the smaller Miami-Luken Inc., while the former chief of H.D. Smith Wholesale Drug Company also said no.

The denials drew an angry response from GOP Rep. David McKinley of West Virginia, where federal figures show 884 people died from drug overdoses in 2016. That gives the state the nation’s highest overdose death rate — 52 out of 100,000 people. Other states with high death rates included Ohio, Pennsylvania and New Hampshire, plus Washington, D.C.

“The fury inside me right now is bubbling over,” said McKinley. He said he found the denial of responsibility “particularly offensive” and he wondered aloud about the proper punishment.

“Just a slap on the wrist, some financial penalty?” he asked. “Or should there be time spent for participation in this? I just want you to feel shame.”

Members of both parties accused company officials of missing signs of suspicious activity. The government requires distributors of controlled substances to report suspicious drug orders to the federal Drug Enforcement Administration and to deny questionable transactions.

The committee’s investigation has found that distributors sent more than 780 million pills of hydrocodone and oxycodone — prescription pain-killers that have caused many deaths — to West Virginia from 2007 to 2012. Around 1.8 million people live in the state.

Investigators said 20.8 million opioid pills were shipped from 2006 to 2016 to Williamson, population 2,900. One pharmacy in Kermit, with around 400 residents, ranked 22nd in the U.S. in the number of hydrocodone pills it received in 2006, according to the investigation.

“Was it the profit motive” that prompted them to continue making dubious sales, asked Rep. Cathy Kastor, D-Fla.

The corporate executives said they’ve improved their detection systems — a promise lawmakers said they’d heard before. The officials also acknowledged responsibility for fixing the problem but said that was divided with others, too. Nearly 12 million people misused opioids in 2016, according to federal figures.

“It’s a shared responsibility among many different players: physicians, pharmacists, state medical boards, state pharmacy boards, DEA” for solving the problem, said Mastandrea.

In some cases, they apologized.

“To the people of West Virginia, I want to express my personal regrets for judgments that we’d make differently today,” said George Barrett, executive board chairman of Cardinal Health.

The Trump administration and lawmakers of both parties have been drawing attention to opioids, a range of pain-killing drugs that can be addictive when misused. They include prescription drugs like hydrocodone, oxycodone and codeine, synthetic opioids like fentanyl that can be made illegally, and illegal drugs like heroin.

House and Senate committees have been working on dozens of bills that include encouraging doctors to use non-addictive pain killers, spurring research on such products, broadening access to treatment and giving financial incentives for drug treatment specialists to work in underserved areas.

In 1994, tobacco company executives testified before the Energy and Commerce panel, then controlled by Democrats. The officials said they didn’t believe cigarettes were addictive, despite evidence to the contrary.

Within four years, the industry reached a settlement to pay states more than $200 billion over 25 years for tobacco-related health care costs.

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New engineering method could overcome barriers in diabetes cell therapy

Pancreatic cell transplants have the potential to be a permanent treatment for Type 1 diabetes. Problem is, the cells have trouble forming the blood vessel networks they need to thrive and provide insulin to patients. So scientists in the U.S. and Japan devised a new tissue engineering method to tackle this blood-supply problem in pancreatic cell transplantation. Using the method, they created pancreatic islets that cured severe Type 1 diabetes when they were transplanted into mice.

Human pancreatic islets tend to lose their blood vessels while being prepped for transplant, and attempts to combat this—including creating new islets from stem cells—have been largely unsuccessful, the researchers, from Cincinnati Children’s Hospital and Yokohama City University (YCU), wrote in their study. So to speed up vascularization in transplanted tissues, the researchers, led by Takanori Takebe of Cincinnati Children’s and Hideki Taniguchi of YCU, created a technique called self-condensation cell culture.

The team tested it with donated human organ cells, mouse organ cells and induced pluripotent stem cells, combining each of these cell types with progenitor cells called mesenchymal stem cells and human umbilical vascular endothelial cells. They also added genetic and biochemical material that triggered the formation of pancreatic islets. Cultured in an endothelial cell growth medium, the “ingredients condensed and self-organized” into pancreatic islets.

“The self-condensation of human and mouse islets with endothelial cells not only promoted functionalization in culture but also massively improved post-transplant engraftment,” they wrote in the study. The transplant treated mouse models of Type 1 diabetes more effectively than did a conventional approach, they reported.

While the study is promising, Takebe warned that more work is in store before it can be used in humans. Transplanting donor cells might provoke a rejection from the recipient’s immune system, while a stem cell-based approach carries the risk of tumors that can arise from residual immature cells.

In fact, multiple companies and academic teams are working to lessen those sorts of risks by finding new ways to encapsulate stem cell-based therapies. Eli Lilly, for one, recently handed over $63 million up front to license Sigilon’s islet cell encapsulation technology, while Semma Therapeutics raised $114 million last fall to move its encapsulated therapy into the clinic.

And there is widespread interest in academia in converting patients’ own cells into diabetes treatments, which could eliminate the risk of immune rejection. In February, researchers from the University of Miami Miller School of Medicine’s Diabetes Research Institute confirmed the existence of progenitor cells that can become insulin-producing beta cells in the pancreas, and a Stanford team is working on converting pancreatic alpha cells to beta cells.

Takebe hopes to further develop his team’s vascularized tissues and examine their potential as a transplantable treatment for diabetes. “This is a life-threatening disease that never goes away, so developing effective and possibly permanent therapeutic approaches would help millions of children and adults around the world,” he said.

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J&J Darzalex gains landmark myeloma approval in first-line patients

Johnson & Johnson’s Darzalex just vaulted ahead of its myeloma competitors—and it has plenty of them.

Monday, the FDA greenlighted the drug—in combination with Takeda’s Velcade and prednisone—in first-line multiple myeloma patients who are transplant ineligible, making it the first monoclonal antibody to ring up an approval in newly diagnosed patients.

The go-ahead is no surprise, considering the stellar data J&J unveiled at December’s American Society of Hematology annual meeting. In a trial of front-line patients, at a median follow-up of 16.5 months, the Darzalex regimen cut the risk of disease progression or death by 50%.

Darzalex has come a long way since its first approval back in late 2015, which came the same month Bristol-Myers Squibb’s Empliciti and Takeda’s Ninlaro picked up their own FDA blessings. The J&J product was initially cleared only for patients who had tried three prior treatments, and it snagged its second-line OK a year later.

Meanwhile, the newest approval marks Darzalex’s fifth in myeloma—and the way J&J’s executives see it, there are plenty more to come, including in the front-line setting.

“What we’ve seen is that the drug seems to benefit with any regimens—with other IMiD-containing regimens, with proteasome regimens … so our general view is that this is a mechanism that can improve on [results from] any established regimen,” Peter Lebowitz, Janssen’s global therapeutic area head of oncology, said in an interview at ASH.

The company’s Janssen unit is currently trialing the hot-shot drug in other front-line studies, one of which is examining Darzalex in combination with an IMid therapy and a proteasome inhibitor. “We want it to be fairly universal that you use the drug with whatever regimen you end up choosing,” Lebowitz said.

https://bit.ly/2woV4hC

Care.Com Reports Q1 Non-GAAP Earnings Per Share Of $0.19

CARE.COM ANNOUNCES FIRST QUARTER 2018 FINANCIAL RESULTS

* Q1 NON-GAAP EARNINGS PER SHARE $0.19

* Q1 GAAP EARNINGS PER SHARE $0.05

* Q1 REVENUE $47.3 MILLION VERSUS I/B/E/S VIEW $46.9 MILLION

* Q1 EARNINGS PER SHARE VIEW $0.13 — THOMSON REUTERS I/B/E/S

https://reut.rs/2roUx9I

Crowd-Funding for Stem Cell Therapy ‘Often Based on Misinformation’

Direct-to-consumer (DTC) marketing messages have bled into crowd-funding campaigns for unproven stem-cell therapies, one study suggested, highlighting the inaccuracies of many claims on the internet.

Because insurers won’t pay for unproven interventions, many patients find their only options are to pay out-of-pocket or to crowd-fund for a stem cell treatment, according to Jeremy Snyder, PhD, of Simon Fraser University in Burnaby, British Columbia, and colleagues.

They identified 408 campaigns on GoFundMe and YouCaring (358 of them on GoFundMe) wherein the efficacy of the treatment in question was often misrepresented:

• 43.6% made statements that were definitive about the intervention’s efficacy
• 30.4% said they were optimistic or hopeful about efficacy
• 15.4% wrote statements of both kinds
• 10.5% offered no efficacy claims

Any time risk was mentioned (n=36), the campaigner said the intervention was no- or low-risk compared with alternative treatments, according to their research letter in the Journal of the American Medical Association.

“Crowdfunding campaigns for unproven stem cell-based interventions underemphasize risks and exaggerate the efficacy of these interventions. These findings suggest that medical crowdfunding campaigns convey potentially misleading messages about stem cell-based interventions. These claims may be especially powerful when embedded within compelling personal narratives,” they said. “The situation parallels that of DTC marketing of unproven stem cell-based interventions, which has been shown to make hyperbolic claims about efficacy and minimize risks associated with their use.”

These risks run the gamut from blindness (after stem cell treatment for age-related macular degeneration) to opportunistic infections as reported by recipients.

For now, what physicians can do is to be aware of the potential for crowd-funding campaigns to help spread inaccurate information, Snyder’s group suggested.

“Clinicians have a role to play in trying to inform their patients about the state of the science on stem cell treatments if they are aware that their patients are considering these treatments. They should point these patients to reputable sources of information on the state of stem cell science,” Snyder told MedPage Today, citing the International Society for Stem Cell Research as an example.

“Too often people use crowd-sourcing to pursue something that is really of dubious scientific merit. Stem cells in particular as an area is problematic. It’s an area where there’s a lot of dubious practitioners offering doubtful therapies,” commented Arthur Caplan, PhD, of NYU School of Medicine in New York City, who was not involved with the study.

Yet it’s important that physicians understand why patients would be doing this, he said.

“It’s a loving, kind thing for many people, to try to raise money. It’s understandable. It’s not inherently a bad thing to want to try to do. At the same time, ask patients if they really understand what’s being offered before they throw away their own money and other people’s money on something that isn’t valid,” Caplan continued. “Say this stuff is a long shot and say be ready with a plan or approach if it doesn’t work.”

The other option the doctor can raise is whether it would be better to enter a clinical trial, he suggested.

Physicians are ultimately in a unique position to make the direct-to-consumer marketplace for stem cells safer and less exploitative, said Paul Knoepfler, PhD, of University of California Davis. “Stem cell researchers can have impact too, but physicians have a special relationship with patients and can probably in some ways more effectively counter the marketing of unproven, for-profit offerings.” Knoepfler was not involved in the study.

These businesses don’t do business across state lines, and are not regulated by the FDA, according to Caplan. Even so, the agency started cracking down on unapproved therapy centers by seizing products and issuing warning letters to individual businesses last year.

Snyder’s group searched for keywords matching 351 U.S. businesses that they knew were marketing stem cell interventions directly to consumers as of the end of 2017. “These are generally treatments where the relevant experts feel that the science does not support marketing these treatments for sale, and that the marketing messages greatly over promise the likely efficacy of these treatments,” Snyder noted.

Altogether, these crowdfunding campaigns requested $7.44 million and received pledges for $1.45 million from 13,050 donors. They were shared 111,044 times on social media.

This is just the beginning, Snyder said. “While individuals purchasing unproven stem cell treatments is not new, the relatively recent phenomenon of crowdfunding for these treatments is very concerning. Crowdfunding gives more people access to these treatments, implicates more people in potentially having their money wasted on unproven treatments, and spreads unsupported efficacy and safety claims through social media to a much wider audience than previously,” he stated.

The study was supported by a grant from the Canadian Institutes of Health Research.

Snyder, Caplan, and Knoepfler disclosed no relevant relationships with industry.

• Primary Source

  Journal of the American Medical Association

  Source Reference: Snyder J, et al “Crowdfunding for unproven stem cell-based interventions” JAMA 2018;319;1935.

https://bit.ly/2KIB90a

How to Answer Popular Behavioral Questions in the Job Interview

A growing number of employers are asking “behavioral questions” in the job interview, so if you’re currently on the job market or considering putting yourself out there, you should spend some time researching the most likely behavioral questions you’ll be asked in your next interview, how you can prepare for these questions, and the best answers to give.

So, what exactly are behavioral interview questions? Unlike traditional interview questions where you’re asked how you might behave or act in a hypothetical workplace scenario or even to list your skills and strengths directly, behavioral questions prompt you to discuss a time in your past when you were faced with a real-life situation and explain how you handled it, hopefully highlighting your relevant skills along the way.

Behavioral interview questions typically start with the interviewer asking something like, “Tell me about a time in your past when…” followed by “how did you deal with it?” By getting a sense of how you’ve handled tough situations in the past or how you’ve achieved your goals, an employer will gain a better understanding of how you’ll perform in their organization.

As such, your answers to behavioral questions should be well-prepared and thought-out so that they highlight your richest professional experiences and your best skills and character traits.

Here are a few of the most popular behavioral questions you’re likely to be asked in a job interview:

“Tell me about a time when you had to deal with conflict and what you did to resolve it.”

• Here’s your chance to showcase your problem-solving skills. Make sure your answer doesn’t dwell too long on the problem or conflict, but instead spend most of your answer explaining the solutions you brought and the positive impact this had on your organization, team, or project.

“Tell me about a big mistake you’ve made at work and how you fixed it.”

• This is the behavioral question’s version of the traditional job interview question “what is your greatest weakness?” So, again, focus most of your answer here on the solution you provided that came after the mistake. Don’t linger on the mistake itself. Also, be prepared to reveal a mistake you’ve made that is authentic and true and that gives you an opportunity to talk about your ability to problem solve, adapt, and improve, but one that isn’t so grave or worrisome that it raises a great big red flag to a potential employer.

“Have you ever had a difficult relationship with a coworker or boss, and how did you address it?”

• This question is essentially designed to figure out how well you play with others and how you handle inevitable workplace conflicts. It’s an attempt to assess your interpersonal skills and whether or not you’ll be an instigator or a calming presence on the job, and it’s also a great way to find out if you’re an effective communicator. It’s not simply enough here to say you resolved a difficult relationship by looking for a new job (even if that’s true too). Be sure to give an example of a workplace relationship that clearly improved as a direct result of your conflict resolution or communication skills.

“Tell me about a time you achieved a difficult goal. What did you do to achieve it?”

• This is your chance to really shine. Give some thought before the interview about the most important skills or traits you’d like to convey to the interviewer, and make sure that whatever scenario you reference, you’re able to make a connection between a singular past accomplishment and the future successes that you will bring to this new position.

“Have you ever had to adapt to a big change at work, and how did you deal with it?”

• This question evaluates your ability to think on your feet, react, and re-strategize in a fast-paced environment. Are you able to quickly re-prioritize and set new goals, remaining calm in times of crisis? Do you get uncomfortable with uncertainty or change and buckle under the pressure? Or are you an agile thinker who is constantly learning, innovating, and evolving even in times of instability? Of course, you want to be seen as the latter, so be sure to highlight a situation where you demonstrated adaptability and positivity in response to change or uncertainty.

https://bit.ly/2wixbbs

Alnylam’s Preclinical Data Supports CNS Delivery of RNA Interference Therapies

Cambridge, Massachusetts-based Alnylam Pharmaceuticals reported preclinical results that supports advancement of its RNA interference (RNAi) therapeutics for central nervous system disorders into the clinic.

The company indicated that it had delivered its novel small interfering RNA (siRNA) conjugates into the central nervous system (CNS). The data was presented at the TIDES: Olignonucleotide and Peptide Therapeutics 2018 Annual Meeting held in Boston this week. The study was performed on rats. A single intrathecal injection of a siRNA conjugate had broad distribution across the brain and spinal cord regions.

RNAi is a natural cellular process where genes can be silenced—turned off. Alnylam is focused on using the technology to treat various diseases caused by lack of appropriate proteins or excess proteins. They have particular potential for preventing or reversing neurodegenerative diseases caused by dominantly inherited genes, such as Alzheimer’s, Huntington’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS).

Alnylam expects to select its first CNS-targeted development candidate this year and file its first investigational new drug (IND) or equivalent in late 2019 or early 2020, with possibly one or more INDs per year after that.

“Over the past 15 years, Alnylam has advanced conjugate-based delivery of investigational RNAi therapeutics with multiple transformative discoveries, paving the way for development of a whole new class of innovative medicines,” said Kevin Fitzgerald, Alynylam’s senior vice president, Research, in a statement. “We have now applied our learnings, including additional chemistry advances, to enable delivery of siRNAs beyond the liver to the CNS, where there are a large number of unmet needs well suited for RNAi therapeutics. As we begin to advance our CNS pipeline, initial efforts are focused on genetically validated CNS targets, use of biomarkers for initial proof-of-concept, and disease settings with high unmet need and a definable path to regulatory approval and patient access.”

On May 3, Alnylam provided its first-quarter financials. For a company with no products on the market, it has $1.6 billion in cash and investments. Revenues for the quarter were $21.9 million, compared to $19 million in the same quarter the year before. The revenues came from its alliance with Sanofi Genzyme and with The Medicines Company.

On the other hand, the company has a number of pipeline products, with one awaiting U.S.Food and Drug Administration (FDA) approval. That is patisiran, an investigational RNAi treatment for hereditary ATTR amyloidosis. It is also being evaluated by the European Medicines Agency (EMA).

It also has ALN-TTRsc02, also for ATTR amyloidosis, which is in Phase I trials, and givosiran for acute hepatitis porphyrias (AHPs). It recently completed enrollment of the first 30 patients of givorsiran in the ENVISION Phase III trial. In addition, it has lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1 (PH1), and several other programs.

The patisiran approval is expected in mid-2018, with a PDUFA date of August 11. If approved, the company has plans to launch the drug in the U.S. shortly afterwards. One issue that could face the company is competition from Pfizer’s tafamidis. Pfizer recently released positive data on its Phase III trial of TTR amyloidosis patients with cardiomyopathy. Not much data was made available, but it did show a 50 percent reduction in mortality and a 40 percent cut in hospitalizations.

Stephen Simpson, writing for Seeking Alpha, notes, “Although these results do suggest that tafamidis could be competitive in the cardiomyopathy and hybrid TTR markets (which wasn’t expected before), it seems unlikely to me that the drug will play much of a role in neuropathy—unlike Alnylam’s drug patisiran, which has been shown to reverse symptoms, tafamidis largely leads to just a slower progression for neuropathy patients. Interestingly, patisiran has also been shown to be more effective when given to polyneuropathy patients previously on stabilizers like tafamidis.”

He goes on to note that Alnylam has a lot going on. “Between Alnylam’s controlled drugs and its partnerships with Sanofi (which controls fitusiran, an RNAi drug for hemophilia in pivotal studies) and The Medicines Co. (which controls inclisiran, an RNAi drug for cholesterol in pivotal studies), Alnylam could be looking at six FDA approvals over the next three to four years.”

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