Save Our Bones Bulletin: Enzyme Inhibitor Points To New Osteoporosis Drug, Daily Osteoporosis Injection Just Approved, Prescription Drug Spending Projected To Grow
In our technological age of instant gratification, many things are easy and immediate. You can order products to be delivered to your door by clicking a button; an app on your phone can tell you the weather right outside your window without you ever having to draw the curtains; and you can access all the information in the world by asking a question aloud to an artificially intelligent assistant.
Unfortunately, this has set up false expectations about other parts of our lives, including our health. The desire to find an instantly effective quick-fix solution to every problem is endemic in the developed world. Even when a tried-and-true corrective course of action is known, the lust for a one-time injectable wonder-drug, or a daily pill that replaces the need to take care of ourselves, is persistent.
Today’s bulletin looks at three news items from the world of Big Pharma, from fledgling research into a new synthetic bone-formation intervention, to the FDA’s latest drug approval, to the incentive driving and supporting all of these actions.
More Osteoporosis Drug Research Underway
Medical researchers at the Endocrine Unit of the Massachusetts General Hospital Department of Medicine have announced their work manipulating the way hormone signalling affects gene expression within bone cells. They aren’t the first to try and build a drug to change how your body builds bone, and they won’t be last.
This research is focused on parathyroid hormone (PTH) and its role in bone formation and resorption. You might know this injectable drug by the name Forteo, a yet-to-be understood drug that has been linked to cancer and many other terrible side effects. The current research is aimed at better understanding how PTH works, particularly in relation to osteocytes, so the researchers deactivated different enzymes in the signaling pathway that leads to bone formation and resorption.
Their first finding was that PTH suppresses a gene called SOST using transcription regulating enzymes HDAC4 and HDAC5. Previous research shows these two enzymes are regulated by other enzymes called SIKs.
Then, experiments with small-molecule SIK inhibitors showed that they also regulate other PTH target genes such as RANKL, which stimulates bone resorption. They found that an SIK2-specific inhibitor called YKL-05-093 mimicked the effects of PTH on gene expression in mice.
The problem was that repeat dosing with YKL-05-093 had “adverse effects” on mice. Given how awful the side-effects of FDA approved drugs can be, these unspecified effects must have been pretty awful for the researchers to deem them unacceptable. The researchers found a closely related compound, YKL-05-099, daily doses of which safely stimulated bone formation in male mice. However, what qualifies here as “safely” is unclear.
The team was surprised to find that YKL-05-099 also reduced levels of osteoclasts – cells responsible for the breakdown of bone – indicating that it had the desired dual effect of stimulating bone formation and suppressing bone resorption.
“We don’t completely understand why YKL-05-099 reduces osteoclasts, but we think the combination could be very useful therapeutically,” says Wein, who is an instructor in Medicine at Harvard Medical School (HMS).
“In addition to concentrating on understanding how this compound inhibits osteoclasts – which may lead us to develop even more specific SIK2 inhibitors – we also need to see if it increases bone mass in an animal model of postmenopausal osteoporosis, such as older female mice that have had their ovaries removed.”1
There’s no harm in better understanding the complex system that governs the process by which bodies create new bone and remove old bone. However, this research is not just in pursuit of knowledge, but is seeking the big payday of selling a patentable synthetic compound to a giant pharmaceutical corporation.
Unfortunately, these types of ‘solutions’ always have undesirable side effects. Especially when, as Savers know, we already have the tools we need to improve the quality of our bones.
We can improve our health and our bones by changing our diets, our lifestyle choices, and our exercise habits. Thousands of evidence-backed studies have proven this, and there are no negative side-effects to living a healthier life… but there are lots of positive ones.
FDA Approves Tymlos, An Injectable Osteoporosis Drug
The FDA has just given its dubious seal of approval to the injectable drug abaloparatide, sold under the name Tymlos. It is intended for the treatment of osteoporosis in postmenopausal women at high risk of fracture, or who have multiple risk factors for fracture, and will be prescribed to women who have been intolerant to, or unwilling to take, other drugs.
The Save Institute has been following the all-too-familiar progression of this drug from new research, to FDA trials, and now to approval. Be on the lookout for doctors attempting to push this drug, as Radius Health, Tymlos’ manufacturer, will surely be sending them reams of information and tempting reasons to prescribe their new drug.
Much like Forteo, and like the compound identified in the research above, Tymlos manipulates PTH to trick your body into building new bone. Here’s an excerpt from the report:
“Abaloparatide is a human parathyroid hormone-related peptide (PTHrP[1-34)]) analog that acts as an agonist at the PTH1 receptor. This results in activation of the cAMP signalling pathway in target cells. In animals, abaloparatide had an anabolic effect on bone, demonstrated by increases in bone mineral density (BMD) and bone mineral content that correlated with increases in bone strength at vertebral and nonvertebral sites.
The FDA’s approval was based on 18-month results from the phase-3 Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) and on results from the first six months of the ACTIVExtend trial, which demonstrated significant reductions in the risk of vertebral and nonvertebral fractures regardless of age, the years since menopause, the presence or absence of a prior fracture (vertebral or nonvertebral), and BMD at baseline.”2
At the end of the day, the FDA has a terrible track record for protecting consumers. Frighteningly, the warning label for abaloparatide includes the risk of osteosarcoma, which is cancer of the bone. It also includes Orthostatic Hypotension, a temporary lowering of blood pressure, which may result in dizziness, palpitations, tachycardia or nausea; Hypercalcemia, an abnormally high level of calcium in the blood leading to symptoms like loss of appetite, nausea, thirst, fatigue, muscle weakness, restlessness and confusion, and problems with the heart, urinary tract, and kidney function; and Hypercalciuria, which is an excess of calcium in a person’s urine that can harm their kidneys.
Tymlos may be Big Pharma’s newest drug, but it brings with it side effects that are typical of osteoporosis drugs. They make bones denser without making them stronger, more resistant to fracture, and they do so at the risk of a long list of dangerous side effects.
US Prescription Drug Spending Will Keep Increasing
A recent prediction of annual U.S. spending on prescription medicines forecasts a 22% increase between 2015 and 2020, leading to a potential peak of $400 billion in 2020. The report was released by IMS Health Holdings Inc, a health care information company.
The figures take into account anticipated discounts, rebates and other price concessions that are common, and they indicate an annual growth rate of 4% to 7%. When wholesale prices are considered, spending increases 46% to as much as $460 billion in 2020.
“The average net price increase for branded drugs was just 2.8 percent in 2015, according to IMS, versus 12.4 percent using wholesale prices.
‘That reflects the new dynamics in the marketplace, where we have heightened competition in several major therapy areas, including diabetes, with manufacturers taking price concessions through rebates,’ said Murray Aitken, executive director of IMS Institute for Healthcare Informatics, which produced the report.
It also reflects more aggressive tactics by pharmacy benefit managers and health insurers to restrict access to certain drugs unless manufacturers agree to hefty discounts, he said.
Research pipelines filled with innovative medicines should ensure a high number of new drug launches by 2020, led by expensive cancer treatments.
U.S. oncology drug spending reached $39.1 billion in 2015, an 18-percent jump, while treatments for autoimmune diseases, such as rheumatoid arthritis, rose nearly 29 percent to $30.2 billion.”3
To put this in context, another report predicting global spending anticipates world-wide prescription drug spending at nearly $1.5 trillion by 2021. That’s based on wholesale pricing, and is up about $370 billion from last year’s spending. The U.S. will account for up to $675 billion of that figure.4
This report, issued by Quintiles IMS Holding, was released in December and is more recent than the IMS report. It also seems to suggest that whereas IMS predicted wholesale U.S. spending of around $460 billion in 2020, 2021 will see a leap to $675 billion.
What are we to make of these staggering figures? They illustrate a truth that we must bear in mind whenever we are interacting with the medical industry, and the pharmaceutical industry in particular, that racks up billions and billions of dollars developing and selling drugs.
As Savers fortunately know, osteoporosis drugs are not necessary. This isn’t to say that improving your health doesn’t require an investment. It does. But a holistic, whole-body approach to changing the way you feel and live asks a different sort of investment. It asks for time, to sleep soundly and care for yourself. It asks for nourishment, from whole and healthy foods to create a balanced diet. It asks for effort, to strengthen your body through regular exercise.
While all of these tasks are simple, it’s no small feat to change your lifestyle. The Osteoporosis Reversal Program was created to provide easy actions and ample support for making these changes. Many of the topics touched upon today, such as the documented dangers of osteoporosis drugs and the value of natural alternatives, are fully explained in the Program.
Stop Worrying About Your Bone Loss
Join thousands of Savers from around the world who have reversed or prevented their bone loss naturally and scientifically with the Osteoporosis Reversal Program.
Seeking knowledge is an important first step to creating change. You’re already on the path to stronger bones, and a fuller life!
Till next time,
1 “Signalling pathway could be key to improved osteoporosis treatment.” Domain-B. October 20, 2016. Web: http://www.domain-b.com/technology/Health_Medicine/20161020_treatment.html
2 “FDA Approves Tymlos for Osteoporosis in Postmenopausal Women.” Managed Care. May 1, 2017. Web: https://www.managedcaremag.com/news/fda-approves-tymlos-osteoporosis-postmenopausal-women
3 “US prescription drug spending to hit $400 billion a year by 2020, IMS reports.” Reuters. April 14, 2016. Web: http://www.foxnews.com/health/2016/04/14/us-prescription-drug-spending-to-hit-400-billion-year-by-2020-ims-reports.html
4 “Global prescription drug spend seen at $1.5T in 2021: report.” Reuters. December 06, 2016. Web: http://www.foxnews.com/health/2016/12/06/global-prescription-drug-spend-seen-at-1-5t-in-2021-report.html