New bone drug Tymlos -- is it safe?
Another new bone drug — Tymlos (abaloparatide) — recently hit the market, approved by the FDA for treating osteoporosis in postmenopausal women.
As always when we get a new entry into this ever-more-crowded market, I wanted to see how Tymlos works in the body and what downsides could be lurking behind all the hype. Is Tymlos safe? I wish I had a new and different message for you about Tymlos. Believe me, it would be nice to be able to say, for once, that the newest product on the bone drug market really is good for bones — and safe for those who take it. Unfortunately, I can’t say this.
Tymlos -- how does it work?
Tymlos, like Forteo before it, works by imitating a natural bone-building process in the body to increase the patient’s bone density. It’s similar to Forteo in that it focuses on the parathyroid hormone (PTH) pathway, except that while Forteo mimics PTH itself, Tymlos mimics a peptide called human parathyroid hormone-related protein (PTHrP) — but the end result is the same: stimulation of the PTH pathway to increase osteoblast activity, with the goal of building denser bone. If Tymlos works along similar lines as Forteo, then it stands to reason that it’s going to have similar drawbacks — and it does.
The side effects of Tymlos -- a deeper look
Like Forteo, Tymlos comes with a warning about osteosarcoma, a rare bone cancer. The warning is based on animal studies that have shown increased rates of this cancer in animals dosed with abaloparatide (Tymlos). Rather ironically, one study cheerfully noted that their results “suggest no increased risk of osteosarcoma would be expected in patients treated with [Tymlos]” in comparison to Forteo — which itself offers a greater-than-normal risk of osteosarcoma, so that’s not much of a recommendation.
Another adverse effect in the warning list is orthostatic hypotension — that is, low blood pressure upon standing, which could lead to fainting or falls (not something you want in a person at high risk of fracture!). High blood or urine calcium levels (the latter in association with kidney stones) are also concerning side effects.
Further,the effects of this drugs on the immune system is really unexplored and only lightly touched upon in the safety trials. Half of the individuals using Tymlos develop antibodies to the drug which in some cases lead to cross-reactivity, and in all cases squantered precious immune system focus and energy.
It’s also notable that a large, double-blind clinical trial with 2,463 women (age 49–86) comparing Tymlos directly to Forteo and placebo, Tymlos significantly outstripped both the placebo group and the Forteo group in terms of participants who had to stop treatment due to side effects such as nausea, dizziness, headache, and palpitations; where the Forteo group had about an 0.7% absolute increase in such side effects over the placebo group (a relative increase of 11%), the Tymlos group experienced a whopping 3.8% increase (a 61% relative increase) in these effects over the placebo group.
How much does Tymlos really reduce fracture?
I bring up the “absolute” vs. “relative” increases in side effects for a reason: The 43% nonvertebral fracture risk reduction in Tymlos-treated patients sounds fantastic until you realize it’s relative risk, not absolute risk. In absolute terms, the placebo group had 2% more nonvertebral fractures than the Tymlos group — meaning for every 100 women who took this drug and dealt with its side effects, 2 were spared a nonvertebral fracture who would’ve had one if they’d done nothing. And how about vertebral fractures? This new drug was only slight more successful at reducing vertebral fractures reporting an absolute reduction of 3.64%. One hundred women have to be treated for 3.64 spinal fractures to be prevented. (Given the exorbitant cost of this drug, that's not such a great return on investment!)
Ultimately, this drug has the same problems most of the others have — it hijacks the body’s natural processes to force a result without consideration for the unintended consequences. Which begs the question: Why not work with the body to strengthen bones the way nature intended?
Hattersley G, Attalla B, Varela A, Smith SY. Comparison of osteosarcoma incidence between abaloparatide (BA058) and PTH (1--34) in long term rat studies. Bone Abstracts (2014) 3 PP302 | DOI: 10.1530/boneabs.3.PP302
Miller PD, Hattersley G, Riis BJ, et al; for the ACTIVE Study Investigators. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016;316(7):722-733. doi:10.1001/jama.2016.11136
Tymlos Prescribing Information. Radius Pharmaceuticals. Web. http://radiuspharm.com/wp-content/uploads/tymlos/tymlos-prescribing-information.pdf