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Sunday, May 13, 2018

Atara Expands T-Cell Immunotherapy Collaboration with Sloan Kettering

Atara Biotherapeutics, Inc. (NASDAQ: ATRA) today announced the Company has expanded its collaboration with Memorial Sloan Kettering Cancer Center (MSK) to develop the next generation of genetically engineered chimeric antigen receptor T-cell (CAR T) immunotherapies. This agreement is the next step in Atara’s strategy to leverage the potential of the Company’s technology platform to develop genetically modified off-the-shelf, allogeneic T-cell immunotherapies to transform the lives of patients with serious medical conditions.
Under the agreement, Atara will gain access to several of MSK’s innovative enabling technologies, including a novel CAR T construct that Atara believes has physiologic T-cell activation properties, as well as methods for designing CAR T immunotherapies. Atara is also entering into an exclusive research collaboration for multiple targets with Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering at MSK, to employ next-generation technologies in developing novel CAR T immunotherapies with applications in oncology, autoimmune and infectious diseases.
Dr. Sadelain stated, “We are eager to work with Atara to continue advancing promising allogeneic T-cell immunotherapy technologies that originated at MSK. The new CAR T technologies seek to overcome persistent therapeutic challenges, such as safety and tolerability, durability of treatment response, and activity in areas of significant unmet medical need that are underserved by the current generation of CAR T immunotherapies.”
“Our earlier MSK collaboration has been highly productive, highlighted by tab-cel™, Atara’s off-the-shelf, allogeneic T-cell immunotherapy currently in Phase 3 development,” said Isaac Ciechanover, M.D., Chief Executive Officer and President of Atara Biotherapeutics. “The deepening of our collaboration with MSK allows us to rapidly advance novel gene-edited CAR T development programs leveraging our existing off-the-shelf T-cell immunotherapy technology platform, manufacturing expertise and research and development capabilities. Going forward, we plan to continue to assemble complementary genetic engineering technologies to grow our pipeline and realize the full potential of our platform.”

Bristol-Myers hasn’t been this cheap in years

Shares of the big pharma behemoth Bristol-Myers Squibb (NYSE:BMY) turned in one of their worst months on record in April. Specifically, the drugmaker’s shares lost a hefty 17.5% of their value last month, according to S&P Global Market Intelligence.
Bristol’s shares were clobbered in April for three reasons:
  1. It was a rough month for nearly all biopharmaceutical stocks, thanks to President Trump’s controversial trade war with China.
  2. Pfizer‘s (NYSE:PFE) management team noted halfway through the month that Bristol was not a top acquisition target due to the company’s current valuation.
  3. Bristol’s Q1 sales narrowly missed Wall Street’s consensus estimate toward the end of the month.

Despite posting stellar revenue growth over the past few years due to the breakout success for its cancer immunotherapy Opdivo, as well as its blood thinner Eliquis, Bristol’s shares are now trading near their 52-week lows after this double-digit drop in April.

Bristol’s former top shelf valuation apparently reflected Wall Street’s strong belief that Pfizer would indeed make a tender offer sometime soon. Pfizer, after all, is now flush with cash after the newly minted tax legislation, and this pairing makes a lot of sense for a variety of reasons.
Just because Pfizer isn’t interested, though, doesn’t necessarily mean that Bristol won’t get taken out this year. Gilead Sciences (NASDAQ:GILD), for instance, could very well emerge as a suitor due to the relatively slow start for its cellular immunotherapy endeavor and accelerating declines in its hep C franchise. Gilead also has the financial capacity necessary to take on such a large deal.
Apart from the possibility of a buyout, Bristol looks like a great pick up at these rock bottom prices simply for its strong organic growth. Opdivo is continuing to rack up new indications at record pace and Eliquis’ sales are also showing no signs of slowing down. As such, bargain hunters may want to take advantage of this dip to grab some shares soon.

Beginning to understand autistic adults’ unique health needs

In the 1990s, the prevalence of autism spectrum disorder (ASD) among children rose sharply. These children are now entering adulthood, yet physicians and scientists know very little about the health outcomes they might face. Most studies of health have focused on children and adolescents.
However, new research published this week by scientists at the University of Wisconsin–Madison found that older adults with ASD may be at greater risk than people without the disorder of developing several , including cardiovascular, urinary, respiratory and digestive issues.
“This is one of the few studies to look at  problems in a primarily middle-aged and older population of  with ASD,” says lead author, Lauren Bishop-Fitzpatrick. “Knowing what  adults with autism are more likely to encounter is critical to provide them with effective care and develop prevention strategies.”
With colleagues, Bishop-Fitzpatrick, assistant professor of social work and a researcher at the UW–Madison Waisman Center, used machine learning – a form of artificial intelligence – to analyze de-identified electronic health records of individuals who had received healthcare from the Marshfield Clinic in central Wisconsin and have since passed away.
They analyzed the health records of 91 individuals with ASD and more than 6,000 individuals without ASD from the same region as comparison. The ratio of patients with and without autism was roughly equal to 1:68, the most recent rate of ASD prevalence in the United States as calculated by the Centers for Disease Control and Prevention.
The researchers found that individuals with ASD had increased risks of developing several health complications, including various cardiovascular issues, hypothyroidism, and other neurological issues. They were at decreased risk of alcohol abuse, hypertension, and of developing metastatic cancers.
Based solely on information from patients’ , the researchers were also able to independently predict with 93 percent accuracy whether or not a specific individual had ASD.
“These findings can help us direct healthcare resources and work on prevention efforts more efficiently,” says Bishop-Fitzpatrick. “For example, knowing that adults with ASD may be at higher risk of developing cardiovascular disease, we can start adapting techniques and healthcare measures that are already in place for the general population to best help adults with ASD.”
Learning more about the healthcare issues of adults with ASD could also help extend their lives. A 2016 study in Sweden found that individuals with ASD died at significantly younger ages – nearly 20 years earlier – compared to those without ASD.
The researchers hope their findings will lead to larger, more comprehensive studies that focus on the health issues faced by older individuals with ASD. Bishop-Fitzpatrick also plans to speak to individuals with autism and their families to understand their individual health issues and concerns at the same time that she works to understand these at the population level.
“Our goal is to create strategies and interventions that can help individuals with ASD live longer and healthier lives and to make sure they have the best quality of life for as long as possible,” says Bishop-Fitzpatrick.
More information: Lauren Bishop-Fitzpatrick et al. Using machine learning to identify patterns of lifetime health problems in decedents with autism spectrum disorder, Autism Research (2018). DOI: 10.1002/aur.1960

Enzyme blocker stops growth of deadly brain tumor

Investigators were able to halt the growth of glioblastoma, an aggressive form of brain cancer, by inhibiting an enzyme called CDK5, according to a Northwestern Medicine study published in Cell Reports.
The discovery of this enzyme’s regulatory influence on  may open the door to a long-awaited improvement upon current therapy options, according to Subhas Mukherjee, Ph.D., research assistant professor of Pathology and first author of the study.
“The mortality rate for glioblastoma has only moderately changed in last thirty years,” Mukherjee said. “The current drug, temozolomide, is somewhat effective when the tumor recurs—and one of the major problems with glioblastomas is they tend to come back.”
CDK5 is a protein kinase, a class of enzymes that modify the function of proteins and play a major role in protein and enzyme regulation. While CDK5 was previously known to be associated with neurodegenerative disorders including Alzheimer’s disease, its involvement with glioblastoma has only been recently documented, according to Mukherjee.
Glioblastoma’s high likelihood of recurrence is driven in part by glioma stem cells, self-renewing cancer stem cells that support the growth of tumors. Mukherjee, who has been investigating these glioma stem cells since he was a postdoctoral fellow at Emory University, conducted a gene screen on Drosophila models with brain tumors against 29 separate models, each with a single gene silenced.
Mukherjee and his collaborators found the flies’ tumors shrunk and the number of cancer stem cells decreased after silencing the gene that coded for CDK5. In humans, they found a large number of patients with glioblastoma also had high levels of the enzyme, after analyzing glioblastoma patient genetic data in The Cancer Genome Atlas, a database of genetic data from 11,000 cancer patients sponsored by the National Institutes of Health (NIH).
“We started running tests in our lab and found CDK5 promotes a high level of stem-ness in cells, so they proliferate and grow more,” Mukherjee said. “We isolated the cells that were most stem-like, and found that they have a high level of CDK5 compared to ones that are less stem-like.”
With the growth-regulating properties of CDK5 established, investigators then applied an experimental CDK5 inhibitor to human glioblastoma cells, finding it stopped tumor growth and caused  to behave less stem-like, losing some of their self-renewal ability.
In addition, they discovered only two of the three main classifications of glioblastoma have highly expressed CDK5, which suggests patients with the third subtype—mesenchymal glioblastoma—might not see the same benefit.
The authors note that the reduction of stem-ness, combined with the drug’s specificity and ability to cross the blood-brain barrier, make it an excellent candidate for a therapy. In fact, Mukherjee is currently working with Northwestern’s Center for Molecular Innovation and Drug Discovery to create an improved, homegrown version of the drug.
“We will hopefully generate some models and start testing within a few months,” Mukherjee said.
Mukherjee predicts that the future treatment might function as a first-line treatment option in coordination with chemotherapy. Preliminary data suggests that CDK5 is central to  recurrence, so a CDK5 inhibitor might conceivably function in two ways—stopping tumors from growing and preventing them from coming back.
“The idea is to kill the remnants and glioma  after chemotherapy,” Mukherjee said. “Those are the  that persist and cause recurrence.”
More information: CDK5 Inhibition Resolves PKA/cAMP-Independent Activation of CREB1 Signaling in Glioma Stem Cells. Cell Reports. DOI: doi.org/10.1016/j.celrep.2018.04.016

Tesla’s safety head leaves for Alphabet’s self-driving-car unit Waymo

A senior Tesla Inc. executive who was the company’s main technical contact with U.S. safety regulators, has left for rival Waymo LLC, according to people familiar the decision.
Matthew Schwall, who had been the director of field performance engineering at Tesla TSLA, -1.30%  , exited the company as the National Transportation Safety Board and other regulators have been investigating multiple crashes involving the electric vehicles.

Waymo confirmed Schwall has begun working for the Alphabet Inc. GOOGL, -0.19%   unit.
Schwall couldn’t be reached for comment, though a person familiar with his move said it was unrelated to issues Tesla is dealing with regarding Autopilot. Tesla didn’t respond to a request to comment.

Drug Prices: Trump Details Multipart Strategy

President Trump spared no sector of the drug distribution chain Friday in announcing his administration’s plan to lower prescription drug prices.
“Everyone is involved in this broken system — the drugmakers, insurance companies, distributors, and pharmacy benefit managers (PBMs) and many others contribute to the problem,” Trump said during an address in the sun-filled White House Rose Garden.
“The government is also partly responsible,” Trump added. “Previous leaders have turned a blind eye to this incredible abuse, but under this administration, we’re putting American patients first.” In fact, “American Patients First” is the formal name for the administration’s plan, which can be seen on the Department of Health and Human Services (HHS) website.
He also singled out Big Pharma for special criticism, noting that drug companies spent $280 million on lobbying last year, “more than tobacco, oil, and defense contractors combined.”
The administration is attacking the problem on several fronts, starting with “ending Obamacare’s twisted incentives that encourage higher drug prices,” according to Trump. “[There are already] some incentives in Medicare Part D drug plans to encourage drug companies to keep their prices low.” He noted that Alex Azar, Secretary of HHS, “used to run [a drug company], and nobody knows the system better than Alex.” Azar headed the U.S. division of drugmaker Eli Lilly before becoming HHS secretary.
Ending the Pharmacist Gag Rule
Trump promised to end the system’s “double dealing that allows middlemen such as pharmacy benefit managers to pocket rebates and discounts that should be passed on to consumers and patients” and end the pharmacist “gag rule” that prevents pharmacists from telling patients if they can get a cheaper deal on a prescription by just paying for it directly rather than going through their insurance company.
Other initiatives Trump mentioned include:
  • Preventing drugmakers from unfairly manipulating the patent system. “Our patent system will reward innovation but won’t be used as a shield to protect unfair monopolists,” said Trump. In a briefing with reporters following the president’s speech, Azar criticized brand-name drug companies for not allowing generic manufacturers access to innovator drug for purposes of FDA-required testing of generic versions to prove bioequivalency.
  • Speeding up approvals of over-the-counter drugs “so that patients can get more medicines without prescriptions.”
  • Forcing foreign countries to start paying more for prescriptions drugs. “In some cases, medications that cost a few dollars in a foreign country cost hundreds of dollars in America,” Trump said. “That is unfair, it’s ridiculous, and it’s not going to happen any longer. It’s time to end global freeloading once and for all.” Trump said he would direct U.S. Trade Representative Robert Lighthizer to “make fixing this injustice a top priority with every trading partner.”
Changes to Medicare Part D
During the 2016 campaign, Trump had repeatedly insisted that Medicare should negotiate with suppliers to bring down prices paid under the program. But the plan released Friday called for only a limited version involving Part D.
“Part D is now 15 years old,” Azar said at the briefing. “When [it started], we had the best tools and were the best at negotiating deals for senior citizens — we drove tight formularies for senior citizens,” he said. “But over 15 years … it got frozen in place, and the private sector kept adapting and learning … how to control the ‘drug spend’ even better. We need to bring the tools available to the private sector to Part D plans so they can negotiate better deals.”
And the system for paying for the drugs dispensed under Medicare’s Part B program also has to change, Azar added. “[Doctors are] paid now on list price plus a markup; they send us a bill and we write a check,” he said. “We’ve got to figure out ways to move those drugs into private Part D negotiations so we can … start getting bargains for seniors and taxpayers.”
Azar also addressed transparency in drug pricing. “We’re having FDA look at how to require in direct-to-consumer [drug] ads that you have to disclose the list price of your drug. It’s material and relevant to know if it’s a $50,000 drug or a $100 drug, because often the patient will have to bear a lot of that cost.”
“The other thing we have to look at is the entire system of rebates with PBMs,” he continued. “Right now, the incentive is for the drug company to have [a high list price] and negotiate rebates [from that]. What if we said, “No rebates, just a flat price,” which would disincentivize drug companies from having higher list prices.
Azar also questioned the way PBMs are paid. “They’re taking it from both sides, getting compensated from insurance companies and from the drug companies they’ve negotiating against,” he said. Instead, perhaps the industry should move toward a “fiduciary model” in which the PBM works for insurance companies or individuals and can’t get paid by drug companies, “so there is a complete alignment of interests.”
Finally, he gave the administration credit for already giving Americans an $8.8 billion break on drug costs, via its approvals of generic drugs.
Reactions
Healthcare groups had mixed reactions to the administration’s proposals. “The AMA [American Medical Association] is pleased the Trump administration is moving forward with its effort to address seemingly arbitrary pricing for prescription drugs,” AMA president David Barbe, MD, said in a statement. “Physicians see the impact of skyrocketing prices every day as patients are often unable to afford the most medically appropriate medications — even those that have effectively controlled their medical condition for years … We hope the administration can bring some transparency – and relief – to patients.”
“We commend President Trump and his administration for their focus on this essential issue,” America’s Health Insurance Plans (AHIP), a lobbying group for the health insurance industry, said in a statement. However, although several of the administration’s proposals will help lower costs, “We are concerned that some proposals would actually lead to higher costs for Americans, because they would weaken the ability of plans to negotiate lower prices.”
“Insurance providers share the savings from negotiations with drug manufacturers by lowering premiums and copays for all consumers,” AHIP continued. However, one of the administration’s proposals “requiring drug rebates to be passed through to Medicare patients at the pharmacy counter would likely lead to higher drug prices from manufacturers, and would lead to higher premiums for seniors, as well as $40 billion in additional costs for hardworking taxpayers.”

Why Are Nursing Schools Rejecting Thousands of Applicants?

Despite a nationwide nursing shortage that continues to worsen, schools across the country are being forced to turn away qualified applicants due to a lack of nursing educators available to teach. With class sizes unable to be expanded, helping bridge the nursing shortage remains a challenging endeavor for nursing schools.
The Bureau of Labor Statistics predicts that the U.S. nursing field will have more than one million vacancies by 2022, leaving hospitals to implement strategies to recruit and retain nurses. According to Beckers Hospital Review, nursing schools rejected over 56,000 qualified applicants from undergraduate nursing programs in 2017. Community colleges and undergraduate and graduate schools are all being forced to turn away prospective nursing students because the schools are just unable to accommodate more students into their programs.
Class size in particular is a significant challenge for nursing schools that don’t have a sufficient number of nursing faculty or enough clinical space available to adequately train students. Another reason schools struggle to hire qualified nursing instructors is the high salaries being offered to working nurses. The U.S. has an annual national nursing faculty vacancy rate of 7%, which is very high. The shortage amounts to over 1,500 nursing educators nationwide — about two teachers per school.
Despite the challenges, nursing schools are developing new strategies to allow them to accommodate more students. Many are addressing the nursing shortage by thinking out of the box with bridge programs like accelerated RN-to-BSN degree programs or programs for veterans with medical experience who want to pursue nursing careers. Many schools are also partnering with local hospitals so that hospital nursing staff can help teach and train students outside of the school setting.
To learn more about the reasons nursing schools are being forced to turn away qualified applicants despite being in the midst of a nationwide nursing shortage, visit here.