New FDA Approval: Parsabiv

Drug

Etelcalcitide [Parsabiv]

Indication

The treatment of secondary hyperparathyroidism in adults on dialysis. 
 

How it Works

Parsabiv is a new calcimimetic. You might say it's a "calcium-sensing receptor agonist" in the parathyroid gland.

In short, there's a receptor on the parathyroid that detects the amount of calcium in the blood stream. When calcium is low, the parathyroid releases parathyroid hormone (PTH). PTH gets more calcium in the blood stream through a variety of mechanisms...but most notably it activates osteoclasts in the bone and causes resorption. Resorption effectively transfers calcium from the bones to the blood (making the bones a little weaker in the process). 

Let's jump back to Physiology: 101 really quick to talk about why secondary hyperparathyroidism is a problem. For starters, remember that the kidney is responsible for clearing ions like phosphate from your system. In chronic renal failure, the kidney doesn't do such a good job of this...and phosphate can accumulate. As a general rule in the body, phosphate and calcium move in opposite directions. If blood phosphate is up, blood calcium is down. And vice-versa. This is because (you may remember from your TPN lecture) that calcium and phosphate combine to form calcium phosphate. This is insoluble and gets excreted from the body...taking calcium with it. Additionally, remember that the kidney helps to convert Vitamin D to its active form; and Vitamin D is really important in calcium absorption from the diet.

So, in addition to accumulating phosphate, patients with renal failure also usually have an actual deficiency in calcium. This causes the parathyroid gland to kick into overdrive, and it goes nuts releasing a bunch of PTH to get blood calcium levels up. Inevitably, this calcium must come from the bones (where almost all of the calcium in your body is stored), which puts patients at extreme risk for osteopenia and osteoporosis. Subsequent hip and spine fractures severely increase morbidity for patients with chronic renal failure.

We initially combat this trend with phosphate binders. We often start by giving calcium carbonate (Tums) with each meal. This binds to phosphate in the GI tract and the Calcium-Phosphate complex will be excreted out. However, we usually can't give calcium as a phosphate binder for too long, because we eventually run into the opposite problem: hypercalcemia. So eventually, calcium free phosphate binders such as sevalamer (Renvela, Renagel) are required. We also usually are giving Vitamin D supplementation.

Eventually (especially in patients with end stage renal disease on dialysis), even that's not enough. And so we use calcimimetics to "trick" the parathyroid gland into believing there is enough calcium in the blood stream. This shuts it down, and stops the "take all of the calcium from the bone" process from happening.

Until Parsabiv, we've only had one calcimimetic on the market (cinacalcet [Sensipar]). 

Notable Adverse Effects

Parsabiv is tricking your parathyroid gland into believing that there is enough calcium in the blood. The obvious risk in this strategy is that you might encounter an actual reduction of calcium in the blood. Hypocalcemia (both symptomatic and asymptomatic) are potential side effects of Parsabiv. Hypocalcemia may present as muscle cramps confusion, or tingling in the extremities. 

Also remember from physiology that calcium plays an important role in muscle contraction; making muscle spasm another potential complication of Parsabiv therapy. 

And (like basically every other drug in existence), Parsabiv can cause nausea, vomiting, diarrhea, or headache. None of these adverse effects occurred in more than 12% of the study population.

Current Place in Therapy

This is the first drug in 12 years to be approved for hyperparathyroidism, so this condition isn't exactly a hot bed of research. Parsabiv was only pitted against placebo in clinical trials, so unfortunately there isn't data to show it's effectiveness compared to Sensipar.

The main advantage of Parsabiv is in the field of compliance. Sensipar is taken PO, anywhere from 2 - 4 times daily. This dosing schedule can lead to quite a pill burden, especially when combined with phosphate binders at every meal and the many other co-morbidities often seen in patients with chronic renal failure who are on dialysis.

Parsabiv, on the other hand, is given as an IV injection after each dialysis session. This is much more convenient (and can improve adherence), because it's administered by a dialysis nurse while the patient is still in the chair. 

The manufacturer of Parsabiv, Amgen, has said that it expects the monthly price of Parsabiv to be on par with the monthly price of Sensipar (also manufactured by Amgen).

Of course, the patent for Sensipar is expected to expire early next year, so at that point Sensipar will likely become considerably cheaper than Parsabiv. This is a similar strategy to what Gilead has been doing while converting all tenofovir formulations to the new tenofovir alafenamide salt. 

Even still, for patients that struggle with the pill burden of Sensipar; Parsabiv will likely present an attractive therapeutic alternative.