A lot of interesting news on multiple fronts in the last 10 days! A couple of surprisingly very positive studies in the cardiovascular area, promising findings on personalized therapies for cancer, how health insurance literally saves lives, use of artificial intelligence for accelerating drug development, how the recent global ransomware attacks hit some in the health care sector, a major study on the opioid addiction epidemic, studies related to longer lifespans, and some tidbits.
HDL drug finally makes good
We all know HDLs are the “good cholesterol” in the bloodstream, and raising their levels – e.g., by increasing exercise or drinking moderately – protects against CVD. Most CVD drugs don’t raise HDLs much except for an investigational class called CETP inhibitors, which can impressively increase HDLs by more than 100%. CETP stands for “cholesterol ester transfer protein” and is a key component of HDLs, allowing them to hand off their cholesterol to other lipoproteins. CETP inhibitors block that transfer and – somehow – raise HDL levels. Yet, years of studies with several CETP inhibitors basically failed – in fact, some actually increased CVD risk.
Until now. Bucking that history, Merck’s recently announced initial results from REVEAL – a large, randomized, double-blind placebo-controlled Phase 3 trial in 30,000 CVD patients – showing its CETP inhibitor, anacetrapib, met its primary endpoint, significantly reducing major coronary events compared to placebo in patients at risk and already receiving an effective LDL-lowering regimen. Merck plans to review the results of the trial with outside experts, and will consider whether to file new drug applications with the FDA and other regulatory agencies. The results of the REVEAL study will be presented in more detail at the European Society of Cardiology meeting on August 29.
Novartis’ canakinumab delivers surprisingly strong results in reducing CV risk
In a somewhat similar vein (or artery), Novartis announced that its anti-inflammatory drug, canakinumab (ACZ885) met its primary endpoint in CANTOS – a large, randomized, double-blind placebo-controlled Phase 3 clinical trial in more than 10,000 patients with inflammatory atherosclerosis – showing it reduced major adverse cardiovascular events. Some experts believe the findings may change the CVD treatment paradigm. The drug is already approved as Ilaris for a number of inflammatory conditions. Like Merck, Novartis plans to provide more details on the findings at upcoming medical meetings.
Personalized cancer vaccines show promise
Two small Phase 1 studies recently published in Nature show promising results with patient-specific vaccines against melanoma. The vaccines home in on tumor-specific neoantigens, which have long been a target for immunotherapy, but actually identifying them only became possible with recent availability of massive sequencing of mutations within tumors, and of machine-learning approaches to predict which ones will bind with a patient’s immune cells (specifically, T cells).
In one report, U.S. researchers used these technologies to develop patient-specific vaccines targeting up to 20 predicted tumor neoantigens, and vaccinated six melanoma patients who previously had their tumors surgically removed. Generally, such patients have about a 50% chance of a recurrence; four of the six patients, however, had no recurrence 25 months later, while the two with a recurrence achieved complete tumor regression following treatment with a checkpoint inhibitor. In a second report, German researchers used a vaccine based on messenger RNA encoding up to 10 neoantigens, rather than the neoantigen proteins themselves. Of eight patients who had no visible tumors at the time they received the vaccine, all remained cancer-free after more than a year. Five others already had tumor regrowth at the time of vaccination but appeared to benefit as well, with tumors initially shrinking in two of them, and one patient experiencing complete remission after treatment with a PD-1 inhibitor.
Insurance not to die for
In the midst of the current health care bill debate, an analysis reported in Annals of Internal Medicine shows that health insurance saves lives and suggests that, if the current proposed health plan goes into full effect, about 29,000 more Americans would die prematurely each year. The analysis strengthens the conclusions of a previous (2002) Institute of Medicine report showing that people with insurance have up to a 29% lower risk of dying than the uninsured. While some politicians have argued health insurance does not affect the death rate, study coauthor Dr. Steffie Wollhandler said, “Losing insurance is lethal and gaining insurance reduces the death rate. That is completely consistent numerically across the different studies. The politicians in Washington need to deal with that as a fact and not pretend there’s disagreement on this issue.” Currently under the ACA, 28 million Americans are uninsured; CBO estimates the proposed health care bill will result in 22 million more Americans without insurance by 2026.
According to PhRMA, the average drug takes 10-15 years for R&D, costs $2.6 billion (including costs of failures) and, even if entered in clinical trials, has less than a 12% chance of being approved. To improve the odds and cut costs, drug companies are increasingly using artificial intelligence to home in more quickly on promising compounds. GSK recently announced a $43 million deal with the Scotland-based startup Exscientia, which also signed a deal with Sanofi in May. Merck, Johnson & Johnson and others are also exploring AI to help streamline the drug discovery process.
In a related story, the Wall Street Journal reported that Biogen completed a study using quantum computers to accelerate 3-D molecular comparisons. Quantum computing is predicted to able to solve problems within the next five years that are beyond even the most advanced computers available today.
Global ransomware attacks on health companies
Merck was one of dozens of companies attacked with the Petya malware virus on June 27, affecting all the company’s computers and paralyzing many of its operations. Additionally, the Pennsylvania-based Heritage Valley Health System was attacked, affecting the “entire health system, including satellite and community locations,” according to the organization’s website. The attacks were part of a global wave that started in the Ukraine and spread internationally. The attacks exploited a Windows vulnerability for which Microsoft provided a patch in March, but many groups failed to install it.
Sobering facts about the opioid addiction epidemic
An in-depth BlueCross BlueShield (BCBS) analysis based on more than 30 million claims describes the complexity of this epidemic, and notes some very concerning facts such as:
CDC: We’re living longer
In late June, the CDC released its 40th annual report on the health of the nation. Some highlights of changes between 1975 and 2015 include:
Genetic mutation linked longer lifespan in men
Scientists reported discovery of a mutation involving the growth hormone receptor and associated with a 10-year longer lifespan in men, but not in women. In the study, published in Science Advances, the researchers showed that the prevalence of the mutation increased with age in four diverse cohorts of men enrolled in various longevity studies. While the mutated growth hormone receptor seems increase growth during youth (the men with the mutation were about 1” taller than those without it), it also appears to slow cell division later in life, thereby slowing aging. The results also raise questions about the use of growth hormone to restore or maintain youthfulness – it may actually have the opposite effect.
And some tidbits…
FDA increases rate of drug approvals in 2017Fierce Pharma reported that the FDA has approved more drugs so far in 2017 than in all of 2016. On June 23, the agency approved Bevyxxa (betrixaban), the 23rd drug approval for the year; the agency approved only 22 drugs throughout all of 2016.
Read More: Drugs.com
Benefits of moderate drinking? What’s the “proof”?As previously reported in Med-Sci Matters, large, retrospective population studies show that moderate consumption of alcohol (up to 1 drink/day for women, 2/day for men) is associated with a mortality benefit – especially against cardiovascular death (but not cancer) – compared to abstinence or heavier drinking. However, no large, randomized, controlled intervention study – a higher standard of proof – has been performed to date.
Now, as reported in the New York Times, NIH has begun a $100 million clinical trial to test the “alcohol hypothesis” in men and women volunteers age 50 and older. The study has generated some controversy because alcohol beverage manufacturers have pledged $67.7 million to help fund the study, and some of the researchers have links to the alcohol industry. However, the principal investigator, Harvard associate professor Kenneth Mukamal, MD, MPH, says the investigators have had no contact with anyone in the alcohol industry in planning the study.