Europe Stands Pat on Hypertension Guidelines

European blood pressure guidelines will stick with the 140/90 mm Hg diagnostic threshold and instead focus on improving control rates through initial two-drug antihypertensive combinations for most patients.

Topline release of new joint European Society of Cardiology (ESC)/European Society of Hypertension (ESH) blood pressure guidelines at the latter’s annual conference in Barcelona on Saturday is to be followed by full publication at the ESC meeting in August.

“There are many consistencies with the U.S. guideline, but there also is a slightly more conservative approach to the threshold and the target,” Bryan Williams, MD, of University College London and the guideline writing committee chair for the ESC, told MedPage Today.

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelinerevised the diagnostic thresholds to 130/80 mm Hg for stage 1 hypertension — what the ESC calls high-normal — and 140/90 mm Hg for stage 2, with pharmacologic treatment for stage 2 and high-risk stage 1.

“Their suggestions are reasonable and pragmatic,” commented William White, MD, a past president of the American Society of Hypertension. “There’s been some criticism of the ACC/AHA 2017 guidelines for a couple of reasons — that it was based so much on one study, SPRINT, and that SPRINT’s population was not below [age] 60 in general and all had risk.”

The European guideline writers shied away from “medicalizing” the 130-140 mm Hg systolic group, Williams said.

Rather, “we still strongly believe that the most important objective is to get all our patients who are treated below 140 systolic. That should be the first target. When you have lower targets, people try to get below that number in the worried well. Let’s try to get everyone below 140.”

The ESC/ESH recommendations included a range for pharmacologic treatment aims from under 140 to 130 mm Hg, with consideration of going below 130 mm Hg for those who tolerate it well, but not below 120 mm Hg.

For people over age 65, the target was below 140 to 130 mm Hg, but not any lower.

“That’s a big change, because in the past the target was 150 to 140 in those over 65,” Williams noted. “The blood pressure targets are more aggressive, but we’re talking about mobile, fit, non-frail elderly.” For the frail elderly and those in residential facilities, there’s not much evidence, so clinicians have to use their judgment, he added.

The American College of Physicians and American College of Family Physicians guidelinesfrom 2017 controversially recommended a 150 mm Hg systolic threshold for diagnosis and treatment of average and lower-risk adults age 60 and older.

“The Europeans have a nice kind of medium here,” White noted.

For treatment, the ESC/ESH guideline aimed to cut clinical inertia that contributes to poor control rates.

“One of the objectives was to simplify treatment recommendations, and we’ve done that,” Williams said. “We know what optimal treatment should be for most people. Why don’t we normalize the concept that the patient should be treated with two drugs as initial therapy? Most guidelines get around to saying that, but don’t say it directly enough. Start with two drugs — we’ve made that completely clear.”

While those just above the treatment threshold or the frail elderly would be exceptions, the emphasis for two-antihypertensive combination therapy for most patients was on single pill combinations, if at a cost acceptable to the healthcare system.

White cautioned, though: “But for somebody who is 140/90 I don’t even know that even I would consider starting two drugs, because I think there are a lot of people who demonstrate really substantial reductions with one drug and they would probably get symptomatically low if you started them on two drugs. That is not a one size fits all.”

Other aspects of the European guidelines to be discussed in more detail with the full release in August are an emphasis on statin therapy for many more hypertensive patients than currently receive them, based on their total cardiovascular risk, blood pressure in pregnancy, hypertension emergencies, resistant hypertension, atrial fibrillation, and anticoagulation, and a stronger recommendation for home and ambulatory blood pressure monitoring.

https://bit.ly/2JDBL9F

FDA OKs chemo-free therapy for chronic, relapsed leukemia

The FDA on Friday approved a fixed-duration chemotherapy-free regimen for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) patients, with or without 17p deletion, the agency announced.

The phase III MURANO trial that led to the approval randomized 389 patients 1:1 to treatment with rituximab (Rituxan) plus either venetoclax (Venclexta) or bendamustine. After a nearly 2-year follow-up, the rate of progression-free survival (PFS) was 84.9% in venetoclax/rituximab compared with 36.3% for bendamustine/rituximab (HR for progression or death 0.17, 95% CI 0.11-0.25, P<0.001).

And the 2-year PFS advantage with the venetoclax combination was seen regardless of chromosome 17p deletion status (with, 81.5% versus 27.8%; without, 85.9% versus 41.0%).

“The approval of the combination of Venclexta plus rituximab for patients with relapsed/refractory CLL or SLL validates the results seen in the phase III trial, including the significant improvement in progression-free survival over a standard of care comparator arm,” said lead MURANO investigator John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia, in a statement. “Progression-free survival is considered a gold standard for demonstrating clinical benefit in oncology.”

The fixed-duration treatment regimen allows patients to stop treatment after 2 years.

Results of the MURANO trial were presented last year at the American Society of Hematology annual meeting and published earlier this year in the New England Journal of Medicine.

Minimal residual disease (MRD)-negativity was also improved with the venetoclax/rituximab combination. At 9 months, the rate of MRD-negativity was 62.4% versus 13.3% with bendamustine/rituximab, as well as at any point during the trial (83.5% versus 23.1%, respectively).

The rate of complete remissions or complete remissions with incomplete hematologic recovery was 8% in the venetoclax group versus 4% in the bendamustine group.

“What we don’t have is any data on how durable those remissions will be,” said Susan O’Brien, MD, of the University of California, Irvine, in an interview with MedPage Todayprior to the new approval. “But I think there is an expectation based on the high MRD-negativity rate that those will be pretty durable.”

The most common adverse events seen among patients with the venetoclax/rituximab combination were neutropenia, diarrhea, upper respiratory tract infection, cough, fatigue, and nausea.

And with the more serious adverse events of tumor lysis syndrome, there could be barriers to widespread use of venetoclax even in this approved, second-line setting.

“To most people in private practice, venetoclax is not regarded as that user friendly, and it’s not just because they are worried about tumor lysis, it’s because of the monitoring” said O’Brien, who explained that patients need to be followed carefully during treatment to ensure that tumor lysis syndrome doesn’t develop, even in those not at high risk.

LAST UPDATED 06.09.2018

• Primary Source

  The New England Journal of Medicine

  Source Reference: Seymour JF, et al “Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia” N Engl J Med 2018; 378(12): 1107-1120.

https://bit.ly/2Mb6h9z

Biogen late-stage clinical chief heads to Sarepta

Gilmore O’Neill, formerly Biogen’s senior vice president, late-stage clinical development, jumped ship and will be Sarepta Therapeutics’ chief medical officer.

While at Biogen, O’Neill held various leadership roles in Alzheimer’s development, movement disorders, acute neurology, multiple sclerosis, pain, neuromuscular disease, cell therapy and rare diseases. He was involved in the eventual approval for Biogen’s drugs Tecfidera, Zinbryta, Plegridy and Spinraza.

In his new position at Sarepta, he will lead all clinical development, medical affairs, pharmacovigilance, and regulatory affairs.

A physician licensed to practice medicine in Massachusetts, O’Neill previously served as a Harvard Medical School clinical instructor and as chief resident in neurology at the Massachusetts General Hospital. His subspecialty focus was on neuromuscular diseases and inherited leukodystrophies. He received his Bachelor of Medicine from University College Dublin and a Master of Medical Sciences from Harvard University.

He replaced Catherine Stehman-Breen, who joined Sarepta in April 2017. Prior to coming on as chief medical officer, Stehman-Breen had been vice president, clinical development and regulatory affairs at Regeneron Pharmaceuticals since 2015. She is currently Entrepreneur in Residence at Atlas Venture and interim chief medical officer.

“I feel extremely fortunate to welcome Dr. O’Neill to Sarepta and to our executive team as we advance our 21 pipeline programs and build ourselves into one of the most meaningful precision genetic medicine companies in the world,” said Doug Ingram, Sarepta’s president and chief executive officer, in a statement. “Gilmore is uniquely positioned to successfully lead our development strategy. He has deep expertise in neurobiology, genetic medicine and clinical development, having driven some of biotech’s most successful clinical programs. And his proven leadership ability and passion for our mission of changing lives through genetic medicine will be essential as we advance toward our goals with a sense of urgency, creativity and purpose.”

This is just another in a long line of prominent executives leaving Biogen in the last year. In August 2017, Alpna Seth, the head of Biogen’s biosimilars division, left to join former chief executive officer George Scangos at Vir Biotechnology. In June of 2017, Paul Clancy, Biogen’s chief financial officer, left to join Alexion Pharmaceuticals. Earlier in the year, Spyros Arvavanis-Tsakonas, chief scientific officer, shifted to part-time visiting scientist after making a deal with Harvard University. In March 2017, Adriana Karaboutis, executive vice president of technology, business solutions, and corporate affairs, left to become chief information and digital officer of National Grid.

O’Neill’s shift is sure to raise eyebrows given his leadership in Alzheimer’s disease at Biogen. All eyes are on the company’s efforts to move its aducanumab through an ongoing Phase III clinical trial in Alzheimer’s disease. Although the company has a strong presence in multiple sclerosis (MS) and its Spinraza for spinal muscular atrophy (SMA) is growing sales, much of its fortunes are tied to the success or failure of aducanumab.

At the same time, the company appears to be broadening its pipeline for neurology-related diseases. Yesterday Biogen inked an exclusive option deal with Tokyo-based TMS for TMS-007 and backup compounds for acute ischemic stroke (AIS). It also recently expanded an alliance with Ionis Pharmaceuticals to develop RNA-based drugs for brain diseases. And in March, it bought a Phase IIb-ready AMPA receptor potentiator for cognitive impairment associated with schizophrenia from Pfizer.

O’Neill said in a statement, “I was inspired to join the Sarepta leadership team by the quality of Sarepta’s pipeline and the sense of urgency within the company to advance these programs and improve the lives of patients. I’m looking forward to making a fast start, and one of my most pressing priorities will be to meet with and learn from the DMD (Duchenne muscular dystrophy) patient community.”

https://bit.ly/2HyNp0k

Pfizer, AbbVie: Nice yields!

AbbVie (ABBV), Pfizer (PFE), Merck (MRK), Bristol-Myers Squibb (BMY), Johnson & Johnson (JNJ) and Eli Lilly (LLY) sport nice yields, concerns about slow growth notwithstanding, Lawrence Strauss writes in this week’s edition of Barron’s: https://bit.ly/2kZngPt

https://bit.ly/2xTc5Bg

Gilead Turnaround This Year?

Jefferies Michael Yee recently sat down with Gilead Sciences (GILD) management, and the meeting reinforced his bullish thesis on the stock, that a turnaround is “happening this year.”

He writes that Gilead executives, including the chief executive, remain confident that the company would hit a trough this year and then resume growth, which will continue into 2019. Moreover, the second quarter should be better than the first, given one-time issues around its Hepatitis C and HIV businesses that weren’t well understood by the Street.

Yee reiterated a Buy rating and $95 price target on the shares today, writing that Gilead is still his “best large-cap idea” and that its turnaround and recovery offer a different narrative than other large biotechs, where the concern is mostly about generic or biosimilar risks in the coming years.

He also notes that M&A is viewed positively for the company, and if Gilead buys “fairly de-risked assets,” the news should be greeted with enthusiasm. Yee believes that longer term, with revenue and earnings growing again in 2019 to 2021, its multiple should expand.

Gilead is down 0.6% to $71.53 at a recent check; the iShares Nasdaq Biotechnology ETF (IBB) is falling 0.1%, to $100.45 and the SPDR S&P Biotech ETF (XBI) is 0.6% lower to $97.21.

https://bit.ly/2sRrYCH

Illumina Extends Supply Pact With Foundation Med, Links to PerkinElmer

Foundation Medicine and Illumina have amended their supply and service agreement and extended the terms of the agreement through June 6, 2023, according to a document filed with the US Securities and Exchange Commission by Foundation Medicine on Thursday.

According to the agreement, Illumina will supply Foundation Medicine and its German subsidiary with sequencers, reagents, other consumables, as well as service contracts to maintain and repair its instruments. Foundation Medicine has committed to purchasing a certain amount of reagents and other consumables every six months. Sequencers and service contract prices will be based on Illumina’s list prices, while reagents and consumables prices are fixed for a set period of time.

Separately, Illumina also said today that it has codeveloped a metagenomic sequencing workflow with PerkinElmer. The workflow combines Illumina’s Nextera DNA Flex library prep kit with PerkinElmer’s automation and will enable DNA to be extracted and sequenced from samples without needing to culture the bacteria.

The workflow is “aimed at significantly improving the discovery of microbiota-related disorders,” Mitu Chaudhary, manager of product management and library preparation solutions at Illumina, said in a statement.

Mark Dupal, global portfolio director or microfluidics and automation, applied genomics at PerkinElmer, added that the automation would “enable greater laboratory efficiency, reduce labor costs, and generate consistent, high-quality data.”

https://bit.ly/2MexSq2

Low-fat diet tied to improved breast cancer survival odds

Breast cancer patients may have a better chance of survival when they follow a low-fat diet heavy in fruits, vegetables and whole grains, a U.S. study suggests.

Researchers studied 19,541 participants in the federally funded Women’s Health Initiative (WHI) who were randomly selected to join a dietary experiment focused on limiting fat intake to 20 percent of calories. Researchers also looked at data for a control group of 29,294 women in the WHI study who didn’t alter their diets.

By the time the researchers had been tracking half the women for at least 8.5 years, 1,764 participants had been diagnosed with breast cancer.

A decade after their diagnosis, 82 percent of the breast cancer patients on the low-fat diet were still alive, compared with 78 percent in the control group.

For women on the low-fat diet who developed breast cancer, this translated into a 22 percent lower risk of death during the study, and these women typically didn’t succeed at reducing fat consumption by the amount suggested in the diet experiment.

“Decades ago, comparison of country-to-country differences in fat intake found countries with higher fat intake like the U.S. and most of Western Europe had higher breast cancer mortality, but subsequent observational studies have had inconsistent results,” said lead study author Dr. Rowan Chlebowski of City of Hope National Medical Center in Duarte, California.

The WHI dietary modification trial is the only full-scale randomized trial addressing this issue,” Chlebowski said by email.

The main goal of the diet experiment was to get women to change their eating habits, not to count calories or lose weight.

Women assigned to change their diets had a series of group and individual counseling sessions with certified nutritionists over the first year of the program, followed by group sessions four times a year for the remainder of the experiment.

After one year, women in the diet group got about 24 percent of their calories from fat compared with 35 percent fat in other participants’ diets. While weight loss wasn’t a goal, women in the diet group weighted about 2.2 kilograms (4.9 pounds) less than other participants.

While the diet experiment was ongoing, 671 women in the diet group and 1,093 who didn’t alter their eating habits developed breast cancer. This difference was too small to rule out the possibility that it was due to chance.

But women on the low-fat diet were less likely to develop certain hard-to-treat tumors.

One limitation of the study is that researchers relied on women to accurately describe their eating habits in questionnaires, the researchers note in JAMA Oncology. Another drawback is that women in the diet group managed only minimal increases in their consumption of fruits, vegetables and whole grains.

Because women in the low-fat diet group did lose weight relative to other participants, it’s also possible that weight rather than the fat content of the diet might explain the differences in cancer survival odds, said Dr. Graham Colditz, a researcher at Washington University School of Medicine in St. Louis, Missouri, who wasn’t involved in the study.

“For lowering breast cancer risk – and cancer risk overall – the most important part of diet is to keep calories in check,” Colditz said by email. “Weight gain and obesity is an important risk factor for postmenopausal breast cancer – and 12 other cancers.”

Not all fat is created equal, either.

“There is no evidence that total fat intake affects the risk of breast cancer,” Colditz said. “There is growing evidence, however, suggesting that type of fat could be important, with diets rich in polyunsaturated and monounsaturated fats possibly lowering risk, and those higher in saturated and animal fats possibly increasing risk.”

SOURCE: bit.ly/2LYypwv JAMA Oncology, online May 24, 2018.

https://reut.rs/2sIGOMx