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Sunday, May 20, 2018

5 interesting plot twists in the Cigna-Express Scripts deal

Months before Cigna began negotiating with Express Scripts, the insurer was in talks with another large publicly traded healthcare company.
But the discussion of a strategic partnership that began in September never progressed into serious negotiations, and the insurer ultimately determined there was more value in acquiring the pharmacy benefit manager, according to a financial filing by the companies this week. The filings didn’t indicate which company Cigna was in discussions with.
A month later, Cigna and Express Scripts executives met to discuss a possible “white label” commercial arrangement, which eventually transformed into acquisition talks. Five months later, the two companies inked a $67 billion deal.

The filing includes several interesting factors that impacted the deal:
  • Despite shopping around after its deal with Anthem fell through in May 2017, Cigna received no acquisition offers or interest from any third parties, prompting it to look for an acquisition.
  • The terms of the deal fluctuated between the beginning of January, when Cigna made its first offer, and the final deal in March. Cigna’s initially offering was $87-$89 per share. Express Scripts balked at that offer and countered weeks later at $102 a share. The two companies eventually settled on a $97.50 per share price.
  • Amazon made a brief appearance in the discussions when the Express Scripts board of directors acknowledged the potential entry of “significant new participants” in the healthcare industry during a December meeting. Another topic of discussion: The CVS-Aetna deal announced earlier that month.
  • Anthem’s decision to terminate its contract with Express Scripts in April of last year factored into the company’s decision to sell. Express Scripts CEO Tim Wentworth also highlighted “recent consolidation trends” as well as the “regulatory and political climate” and “continued competitive pressure” as reasons the board should seriously consider Cigna’s offer.
  • The regulatory termination fee tied to the deal reach as high as $3.25 billion, part of the counteroffer proposed by Express Scripts in February. The two companies eventually agreed Cigna would pay a $2.1 billion breakup fee if the Department of Justice doesn’t approve the deal.
Express Scripts and Cigna expect the deal to close by the end of the year.

In Type 2 diabetes, intermittent fasting may raise risk

New research suggests that intermittent fasting may raise insulin levels, damage pancreatic cells, and increase the amount of abdominal fat.
plate with clock on it
Intermittent fasting may be a popular diet, but it may also harm our metabolic health, suggests a new study.
The so-called intermittent fasting diet has been gaining more and more traction among people who want to lose weight quickly.
This popular diet consists of “fast” days, where one drastically restricts their calorie intake — to a quarter of the daily dose or less, for instance — and “feast” days, where the person dieting can eat whatever they please.
Sometimes referred to as a dieting “fad,” intermittent fasting has become popular in recent years, due to its suggested benefits of increasing lifespan and staving off cancer.
Indeed, some animal studies have indicated that intermittent fasting may lower the risk of cancer, while observational studies have shown that people whose religion has them fasting regularly live longer than seniors who do not fast.
But could there also be downsides to intermittent fasting? Research presented at the European Society of Endocrinology annual meeting — which took place in Barcelona, Spain — suggests that the dieting practice may have serious consequences for a person’s metabolism.
Specifically, the new study — led by Ana Cláudia Munhoz Bonassa, a researcher at the University of São Paulo in Brazil — suggests that intermittent fasting may impair the normal activity of the pancreas and the production of insulin, which may, in turn, raise the risk of type 2 diabetes.

Intermittent fasting may lead to diabetes

The researchers were prompted in their endeavor by older studies suggesting that fasting for a short period of time increases oxidative stress and the production of free radicals.
Oxidative stress and excessive levels of free radicals have been suggested to speed up the aging process and to damage our DNA, raising the risk of cancer, cardiovascular disease, and neurodegeneration.
To find out whether intermittent fasting does indeed generate free radicals, Bonassa and her colleagues placed healthy, adult rats on the diet for a period of 3 months.
During this time, the researchers measured and monitored the rodents’ insulin levels and function, their body weight, and their free radical levels.
At the end of the dieting period, the rats had lost weight, as expected. However, the distribution of their body fat changed unexpectedly.
The amount of fat tissue in the rodents’ abdomen increased. Belly fat has been shown by recent studies to be deeply linked with type 2 diabetes, with some research even suggesting a molecular mechanism through which the former may lead to the latter.
Additionally, Bonassa and colleagues found damage in the insulin-secreting pancreatic cells, as well as higher levels of free radicals and signs of insulin resistance.
The study’s lead author comments on the findings, saying: “We should consider that overweight or obese people who opt for intermittent fasting diets may already have insulin resistance.”
“[S]o,” Bonassa continues, “although this diet may lead to early, rapid weight loss, in the long-term there could be potentially serious damaging effects to their health, such as the development of type 2 diabetes.”
This is the first study to show that, despite weight loss, intermittent fasting diets may actually damage the pancreas and affect insulin function in normal healthy individuals, which could lead to diabetes and serious health issues.”
Ana Cláudia Munhoz Bonassa
In future, the scientists plan to study in more detail the damaging effects of intermittent fasting on the normal functioning of the pancreas and the insulin hormone.

Saturday, May 19, 2018

Why new Ebola outbreak terrifies public health authorities

A new outbreak of the Ebola virus that has killed at least two dozen people has set public health officials scrambling to contain the epidemic as it threatens to spread far beyond the remote jungles of the Congo River Basin — and raises new questions about the World Health Organization’s (WHO) preparations for the next killer virus.
The U.S. government is preparing its most direct response yet to the outbreak that appears to have begun in April, readying staffers from the Centers for Disease Control and Prevention (CDC) to deploy to multiple communities in the Democratic Republic of Congo.
Ministry of Health officials first identified cases of viral hemorrhagic fever when it reached the town of Bikoro earlier this month. On Thursday, officials said a new case had been identified in Mbandaka, a city of 1.2 million.
The new case in Mbandaka has raised the alarm among public health officials because it is the first time the virus has ever landed in a city that sits directly on the Congo River.
In all eight of the previous known Ebola outbreaks in the Democratic Republic of the Congo, the virus has been contained within remote jungle villages or relatively small towns, where isolated populations are less likely to spread the disease.
But the Congo River is effectively the region’s highway system. Barges and boats travel from Kisangani in the east through major cities including Bumba, Mbandaka — and eventually Kinshasa, the capital of the DRC and home to more than 11 million people, as well as Brazzaville, the capital of the Republic of Congo.
“The Congo River connects three national capitals and multiple other large cities,” said Jeremy Konyndyk, who served as head of USAID’s Office of Foreign Disaster Assistance during the 2014-2015 outbreak. “The fact that there are now several cases in an urban center of more than a million people underscores the potential for this outbreak to get out of control.”
If the Ebola virus traveled upriver from Bikoro to Mbandaka, some officials wonder, has it also traveled downstream toward Kinshasa, which offers direct air traffic to cities including Brussels, Paris, Dubai and Lagos, Nigeria?
“We don’t know what’s happening along the river, because the river is used by a lot of barges,” said Pierre Rollin, one of the world’s leading experts on the Ebola virus at the CDC. “None of the outbreaks have been by the river or in the big towns. So we have a lot of caution before claiming we know what’s going on.”
Previous outbreaks have been snuffed out in the Congo, Rollin said, because the area is so remote that humans did not have a chance to travel far enough to transmit the virus before succumbing.
That was not the case four years ago in West Africa, where the virus spread widely across international boundaries. Commercial and cultural travel throughout Guinea, Liberia and Sierra Leone — across borders drawn a century and a half ago by colonizers with little regard for traditional tribal boundaries — is far more common than it is in the Congo.
The present outbreak has raised anew questions about WHO and its capacity to respond to deadly viral threats. In the wake of the West African outbreak ago, when the ill-prepared WHO endured withering criticism for its lackluster response to the initial round of cases, the agency has undergone a remarkable round of self-flagellation, reorganizing to prioritize emergency preparedness and response while cutting bureaucracy.
“We’ve seen WHO activate much more quickly, at much larger scale, and in more effective partnership with players like” Doctors Without Borders, said Konyndyk, who sat on an independent panel that advised WHO on reforming its emergency functions after the West Africa outbreak.
The first WHO investigative team arrived in Bikoro on May 5, about a month after the first suspected cases are likely to have emerged in Ikoko Impenge. A logistics team arrived on May 9, and the United Nations began daily flights carrying supplies and personnel between Kinshasa and Mbandaka on May 13.
Tedros Adhanom Ghebreyesus, the WHO’s director general, visited Bikoro on May 13, in part to show the urgency of the situation.
“A major lesson learnt from the West Africa Ebola outbreak was that WHO needed a flexible fund to rapidly respond to outbreaks and emergencies,” Tarik Jasarevic, a WHO spokesman, said in an email from Geneva. The agency’s new Contingency Fund for Emergencies, already activated in the Congo, has made cash available to responders far more quickly than in the case of West Africa.
Still, some wonder why it took the Congolese Ministry of Health and the WHO a month to spot the virus in the first place.
“We are doing better at response, but not much better at rapid detection, which is important,” said Tom Frieden, the former CDC director who now runs the public health organization Resolve to Save Lives. “This was spreading for a while before [it was] recognized.”
Aiding the response further is a new vaccine, finalized in the last days of the West Africa outbreak. About 4,000 doses of the vaccine are headed to the epicenter of the new outbreak, where they will be used in two ways: First, health care workers, those most vulnerable to exposure, will be vaccinated. Then, those who have come into contact with anyone infected, and the contact’s contacts, will be vaccinated, a practice known as ring vaccination.
“That part should really add another arm to the response. It’s not the response by itself, because you still have to do all the rest,” Rollin said.
The Democratic Republic of the Congo is also far more prepared to respond to an Ebola outbreak because the virus is known to be endemic to the region. The first modern outbreak of the Ebola virus occurred in the village of Yambuku, about 370 miles from the site of the present one, back in 1976.

Cantor Fitzgerald: 18 Drug Companies With Catalysts Worth Watching

The biotech analysts at Cantor Fitzgerald have a packed calendar: here are some of the dates they’re tracking and why they’re important.
  • Mallinckrodt PLC MNK 2.3% is expected to release Phase 4 interim Acthar data for multiple sclerosis at the end of May, rheumatoid arthritis in June and systemic lupus erythematosus at some point in the second quarter.
  • Mylan NV MYL 1.05%’s Neulasta and Advair biosimilars have June 4 and June 27 Target Action Dates, respectively. Cantor forecast June oral arguments for challenged Restasis patents and a second-quarter launch of Cimduo.
  • Teva Pharmaceutical Industries Ltd (ADR) ADR TEVA 0.52%’s injectable CGRP fremanezumab has a June 16 PDUFA date, and Cantor anticipates approval and launch before the end of the year.
  • Valeant Pharmaceuticals Intl Inc VRX 0.5% is expected to secure approval for Duobrii June 18 and release Phase 3 data for IPD-123 in the second quarter.
  • Arsanis Inc ASNS 1.88% will report Phase 2 interim results for ASN100 in late June.
  • Dermira Inc DERM 0.83%’s DRM04 has a June 30 PDUFA date, and management will host an investor day May 24.
  • Nabriva Therapeutics PLC – ADR NBRV 4.83% is expected to report Phase 3 Lefamulin data in late spring.
  • Amneal Pharmaceuticals Inc AMRX 2.14% plans to launch generic Welchol and begin its Rytary trial with Teva sometime in the second quarter.
  • Aclaris Therapeutics Inc ACRS 1.99% is expected to release Phase 2 data for ATI-502 in the second quarter.
  • Shire PLC (ADR) SHPG 1.19% anticipates approval for its Covington manufacturing facility in June or July.
  • Heron Therapeutics Inc HRTX 2.1% expects top-line results for its HTX-011 studies toward the end of the second quarter.
  • Cidara Therapeutics Inc CDTX 1.05% plans to announce a development candidate midyear.
  • Spero Therapeutics Inc SPRO 0.33% will report Phase 1 data for SPR994 by mid-2018 with the second quarter bringing results for a Phase 1b study of SPR741 and preclinical study of SPR206. SPR994 will begin a Phase 3 trial at the end of the year.
  • Theravance Biopharma Inc TBPH 0.69% will report Phase 2a data for TD-9855 by the end of July, has a Nov. 13 PDUFA date for TD-4208 and will begin reporting Phase 1b data for its JAK inhibitor in the back half of 2018.
  • Allergan plc AGN 1.12% has a PDUFA date for Esmya in August; anticipates Sarecycline approval and the release of Abicipar Phase 3 data in the second half of 2018; and will report Rapastinel Phase 3 data in 2019. Cantor Fitzgerald expects Phase 2b data for oral CGRP atogepant and Phase 2 data for pilocarpine/oxymetazoline in the second half of 2018.
  • Endo International PLC ENDP 1.61% will report Phase 3 data for Xiaflex by the first quarter of 2019.
  • Paratek Pharmaceuticals Inc PRTK 1.32% will report Phase 2 data for Omadacycline cUTI in the second half of 2019.
  • Opko Health Inc. OPK 18.24% is expected to release interim Phase 2b data for OPK88004.

Study supports usual medical care plus chiropractic care for low back pain

Bottom Line: U.S military personnel with low back pain who received usual medical care plus chiropractic care reported moderate improvement in their pain intensity and disability compared with patients who received usual medical care alone.
Why The Research Is Interesting: Low back pain is one of the most common reasons service members in the U.S. military seek medical care. Common therapies for low back pain include nonsteroidal anti-inflammatory drugs, opioids, spinal fusions and edpidural steroid injections. An opioid crisis in the United States has created an urgent need to evaluate cost-effective and low-risk nonpharmacological treatments for low back pain. One of those options is chiropractic care.
Who and When: 750 active-duty U.S. service members enrolled in a clinical trial at three military sites (250 at each site) conducted from September 2012 to February 2016
What (Study Interventions and Measures): Usual medical care (self-care, medications, physical therapy and pain clinic referral) or usual medical care plus chiropractic care (spinal manipulation in the low back and adjacent areas plus additional procedures such as rehabilitative exercise, cryotherapy, superficial heat and other manual therapies) over six weeks (interventions); low back pain intensity and disability scores (main outcomes)
How (Study Design): This was a clinical trial. Clinical trials allow for the strongest inferences to be made about the true effect of an intervention such as a medication or a procedure. However, not all clinical trial results can be replicated in real-world settings because patient characteristics or other variables may differ from those that were studied.
Authors: Christine M. Goertz, D.C., Ph.D., formerly of Palmer College of Chiropractic and now with Spine IQ (The Spine Institute for Quality), Davenport, Iowa, and coauthors
Study Limitations: Differences in participant characteristics, treatments received and outcomes across sites, as well as a short follow-up
Study Conclusions: Changes in pain intensity and disability reported by U.S. military personnel in this clinical trial that supports usual medical care plus chiropractic care for low back pain are consistent with existing literature on spinal manipulation therapy in both military and civilian populations.

New blood test could help avoid more than 40% of prostate biopsies

A multi-center study that validates the clinical performance of IsoPSA – a new blood test that has proven to be more accurate in predicting overall risk of prostate cancer than standard prostate-specific antigen (PSA) – will be presented during a special press conference at the 13th Annual Meeting of the American Urological Association (AUA) on May 18 in San Francisco.
Results showed that more than 40 percent of biopsies could have been avoided in both the preliminary study (45.1 percent) and validation study (47 percent), suggesting that use of IsoPSA may substantially reduce the need for biopsy, and may thus lower the likelihood of overdetection and overtreatment of nonlethal prostate cancer.
The study, Prospective Validation of the IsoPSA Assay for Detection of High Grade Prostate Cancer, was conducted as a follow-up to early studies which demonstrated that IsoPSA, a structure-focused protein biomarker, may be an effective means of discriminating between high-grade prostate cancer (Gleason≥7) and low-grade/benign disease (Gleason=6).
The research team, led by Cleveland Clinic’s Eric Klein, M.D., conducted a multicenter validation trial and evaluated performance data with a new cohort, including cutoff parameters derived from a preliminary study, using the detection of cancer by biopsy as the endpoint.
“To be clinically useful, a biomarker must be both tissue-specific and cancer-specific. While PSA is prostate-specific, it is not specific for prostate cancer, leading to diagnostic inaccuracy and too many unneeded biopsies,” said Dr. Klein, chair of Cleveland Clinic’s Glickman Urological & Kidney Institute. “IsoPSA fulfills both the tissue- and cancer-specificity needed for a useful biomarker, and this validation study shows that it can more accurately detect high-grade cancer and reduce the rate of unneeded biopsies in patients at low risk of this disease.”
The IsoPSA test was developed by Cleveland Diagnostics, a company co-founded by Cleveland Clinic, in which it has financial interest. Dr. Klein has no personal financial interest in the company. Mark Stovsky. M.D., a Cleveland Clinic urologist and co-author on the study, has a leadership position (Chief Medical Officer) and investment interest in Cleveland Diagnostics. In late 2017, Cleveland Diagnostics and Genomic Health announced an exclusive licensing agreement to develop and commercialize the IsoPSA test.

FDA says harvest season over for E. coli-linked romaine lettuce

The U.S. Food and Drug Administration said on Wednesday the harvest season for romaine lettuce, linked to the multi-state E. coli outbreak, was over and it was unlikely that it was still available in stores due to its 21-day shelf life.
The reported strain of E. coli, which produces poisonous substances known as Shiga toxins, can cause severe abdominal cramps, bloody diarrhea and vomiting.
The Centers for Disease Control and Prevention said on May 2 one person from California had died related to the E. coli outbreak.
The last shipments of romaine lettuce from Yuma, Arizona were harvested on April 16, according to the FDA. (bit.ly/2GT7v6b)
Twenty-three more people fell ill since the last update on May 9, bringing the total to 172 people from 32 states, the CDC said on Wednesday. (bit.ly/2HhtHu6)
Three more states — Iowa, Nebraska, and Oregon — have also reported cases, the CDC said.