This edition of Med-Sci Matters includes recent promising findings with type 1 diabetes, heart disease, cancer and human “healthspan”; the cost-benefit battle with a PCSK9 inhibitor; questions about the rigor of FDA accelerated approvals; and – not for geeks only! – “teleportation” of DNA.Advances in treating type 1 diabetes
As reported in New Scientist, for the first time, a stem-cell implant is being used to treat type 1 diabetes. The study, by the California-based company Viacyte, has so far enrolled two patients. A credit-card-size implant, called PEC-Direct, containing progenitor cells derived from stem cells, was placed under the patients’ skin. Blood vessels grew and nourished the cells, which matured after about 3 months into insulin-producing pancreatic islet cells that respond to blood sugar levels and release insulin as needed. If consistently successful, the treatment could free people with type 1 diabetes from insulin injections, though they would have to take immunosuppressants to prevent rejection of the implanted cells.
And a second “first” for treating type 1 diabetes: immunotherapy was shown to successfully stabilize the disease in the early stage, according to a report of a trial in 27 patients published in Science Translational Medicine.
Yes, it can…akinumab! The potential roles of inflammation across various disorders such as heart disease and cancer have long been recognized, but few well-controlled studies have proven anti-inflammatory therapies produce beneficial outcomes. Newly published findings from a trial with more than 10,000 patients show the Novartis drug canakinumab significantly reduced the risk for heart attack and stroke by 15% in high-risk patients with inflammatory atherosclerosis (NEJM); other findings show it also reduced the risk of lung cancer in smokers by 67%, and the risk of lung cancer mortality by 77% (Lancet). However, as reported in the New York Times, since the drug suppresses part of the immune system, it increases the risk of infections. Indeed, deaths from infection in the study appeared to match lives saved by the drug, so there was no significant benefit on overall mortality. Exerting powerful anti-inflammatory action by inhibiting the interleukin-1β pathway, canakinumab is currently marketed under the brand name Ilaris for treating a type of juvenile rheumatoid arthritis and other rare disorders. The new findings likely augur intensified research with anti-inflammatory agents against these and possibly other chronic diseases.
Worming our way to better health?Of course, increasing human lifespan is a laudable research goal, but alone it would likely be accompanied by increased frailty and enormous health care costs. Extending “healthspan” – the time that individuals remain healthy and free of age-related infirmities – is therefore an important goal of aging research. Researchers from Emory University published findings in PNAS showing that small molecules called indoles, produced by beneficial “commensal” microbiota and found in cruciferous veggies, extend healthspan in geriatric worms, flies and mice, without effects on lifespan. Indoles may represent or lead to a new class of therapeutics that improve how we age vs. simply extending how long we live (though achieving both would be nice!).
Dueling cost-benefit studiesA recently published health economic analysis in JAMA concluded that, based on the quality-adjusted life-year (QALY) benefits from improved cardiovascular outcomes, the PCSK9 inhibitor Repatha merited an annual cost of $4,500, about one-third the current cost of about $14,500 (not counting rebates and other discounts). Within one day, Amgen fired back with a study in JAMA Cardiology showing that Repatha is cost-effective at $9,700 a year – about what the drug costs after rebates and discounts, according to Amgen. With drug costs being one of the biggest current issues in health care, we can expect other similar “point-counterpoint” analyses going forward.
Disapproving of approvalsTwo studies published in JAMA show that many drugs granted FDA accelerated approval (AA), as well as devices approved for modified uses based on premarket approval supplements, lack clear evidence of safety and effectiveness. In granting AA, FDA often allows drug manufacturers to submit studies based on weaker, surrogate endpoints – usually biomarkers that change more quickly and are easier and less expensive to track than “hard” clinical endpoints. A condition of approval, however, often includes postmarketing confirmation of efficacy based on randomized controlled trials using clinical endpoints. The drug study showed that 14 of 22 drugs granted AA (from 2009-2013) did not undergo such follow-up studies, and 71 of 78 medical device modifications (from 2006-2015) were approved based on a single clinical study with only 185 or fewer patients.
Not for geeks only: The amazing DNA molecule maker!
Email DNA, RNA, proteins, viral particles for a vaccine? It’s now possible with a prototype “digital to biological converter” called the BioXP 3200. Not yet commercially available, the machine can produce customized DNA molecules from digital sequencing instructions and DNA building blocks of short nucleotide chains called “oligos,” all fully automated. Developed by innovative scientists from Synthetic Genomics in La Jolla, CA, the device could provide, for example, DNA or RNA for rapidly making a vaccine against a deadly virus – even in a remote country on the other side of the world. Or, as one of the developers has speculated, to “transmit” life to other planets!