Genetic markers: Do you approve?
For the first time ever, the FDA has approved a therapy based on a tumor’s genetically-defined biomarker rather than the tumor’s type or location in the body. This new approach to drug evaluation is thought by experts to be a major milestone in precision medicine and good news for many biotech companies. Specifically, on May 23, the FDA granted accelerated approval of an expanded indication for Merck’s Ketruda (pembrolizumab) to include adults and children with unresectable or metastatic solid tumors that are “microsatellite instability-high” or “mismatch repair deficient.” Keytruda was previously approved for advanced melanoma, advanced non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma and urothelial (e.g., bladder) cancer.
First genome editing in the human body
While researchers have edited the human genome in the past, it was always done with cells outside the body (ex-vivo); after the genetic modification was complete, the genetically altered cells would be transferred back into the individual. Now, Sangamo Therapeutics is conducting clinical trials in which genes will be altered in cells in the body – the first time this in vivo approach to gene editing has been done. The researchers will use a special, non-infectious virus called an adeno-associated virus to deliver DNA “scissors” called zinc finger nucleases to snip open a specific portion of DNA in the patient’s liver cells, as well as to incorporate the functional gene at that location. The FDA has granted orphan drug and fast track designations to the therapy. Also related: Sangamo and Pfizer are collaborating on gene therapy (different than gene editing) for hemophilia A, the most common form of the disorder.
Hot off the presses: CBO, JCT score AHCA vs. ACA (FYI)
Yesterday, the Congressional Budget Office (CBO) and Joint Committee on Taxation (JCT) released their scoring of the latest version of the American Health Care Act (AHCA), the Republican bill to repeal and replace portions of the Affordable Care Act (ACA). The agencies estimated that the AHCA would reduce federal deficits by $119 billion over the coming decade, but increase the number of uninsured people by 23 million relative to current law.
U.S. health care access and quality just behind… Estonia!
The AHCA will have its work cut out for it, given findings from the first-ever global study comparing health care access and quality among 195 countries. The report, published in Lancet, assessed 32 causes of deaths that could have been avoided by timely and effective medical care (“amenable deaths”), and scored each country on a health-care quality index. Among the findings: the U.S. ranked #35 out of the 195 countries, just behind #34, Estonia. As reported in the Wall Street Journal, lead researcher Christopher Murray described the U.S. ranking “an embarrassment,” noting our health spend per capita of $9,000/year is more than any other country’s. He added, “Having a strong economy does not guarantee good health care (and) having great medical technology doesn’t, either.” The top country? Andorra, a small country in the Pyrenees mountains, population 85,000 and an economy based on tourism. In 2nd to 10th place, respectively: Iceland, Switzerland, Sweden, Norway, Australia, Finland, Spain, Netherlands and Luxembourg.
Testing 1, 2, 3, testing…not!
According to a systematic review in BMJ, new medications that receive FDA approval based on limited evidence aren’t always proven to work after they’re on the market. The analysis examined 117 novel drugs approved for 123 indications approved by FDA from 2005-2012 based on just one pivotal trial, pivotal trials that only used surrogate markers of disease, or both. The investigators found 35% of these indications had no follow-up postapproval studies at all, and only 7.3% had one or more postapproval, randomized, controlled, double-blind studies with a clinical outcome as the primary endpoint.
Even moderate drinking raises breast cancer risk
The relationship of alcohol intake and mortality has long been known to have a “J-shaped” curve: moderate drinking (no more than 1 drink/day for women, 2 for men) is associated with the lowest risk for total and cardiovascular death (the bottom of the “J”) compared to no intake (the left side of the “J”) or high intakes (the right side of the “J”). However, a number of studies suggested cancer risk and death were exceptions to the J-shaped curve; instead, risk rose linearly from no to moderate to high intakes. Now, a new analysis finds a linear relationship specifically for breast cancer, with even moderate drinking increasing risk a bit, by 5% before menopause and by 9% after menopause. The good news? The study also found evidence (albeit limited) suggesting breast cancer risk dropped with moderate exercise; and eating more dairy foods, non-starchy vegetables and fruits and vegetables rich in carotenoids (think colors – red, yellow and orange). The analysis was part of a large report on the effect of many factors – diet, exercise, lactation and body weight – on breast cancer risk. It was based on 119 studies that included clinical data on 12 million women and 260,000 cases of breast cancer.