FDA Approves Crizanlizumab, A New Drug For Sickle Cell Disease

It isn’t the easiest drug name to pronounce, but crizanlizumab-tmca will be the first ever available targeted therapy for sickle cell disease. On Friday, the U.S. Food and Drug Administration (FDA) announced that they have given Novartis the go-ahead to begin marketing Adakveo, the somewhat easier to say brand name for crizanlizumab-tmca.

This is positive news for not only the approximately 100,000 Americans who are currently suffering from sickle cell disease, according to the Centers for Disease Control and Prevention (CDC), but also everyone else. After all, the disease continues to cost our society lots of money. A study published in the journal Pediatric Blood and Cancer in 2009 found that in 2005 alone sickle disease cost an average of $11,702 for children covered by Medicaid insurance and $14,772 for those covered by employer-sponsored insurance. Things have undoubtedly gotten more costly since then because when is the last time that you heard of healthcare having gotten cheaper over the past 15 years?

Sickle cell disease is an inherited condition that results from a mutation in your genes that produce hemoglobin. Hemoglobin is the protein in your red blood cells that help the cells carry oxygen like little red Ubers through your blood vessels. If you haven’t figured it out yet, you and your body kind of need oxygen to survive. Normal hemoglobin is called Hemoglobin A. Just think “aaayyyy,” this is normal hemoglobin.

Your red blood cells are supposed to look like little doughnuts with no holes in them, so-called bi-concave discs. Here is a picture of scientist holding up a model of a red blood cell, otherwise known as an erythrocyte:

The model is on the left and the scientist is on the right. Note that red blood cells don’t tend to be this large. For an erythrocyte to be larger than a man’s head, the man’s head would have to be smaller than 6 to 8 μm in diameter.

The mutation in sickle cell disease results in a different type of protein, called Hemoglobin S, being produced rather than Hemoglobin A. Remember S for sickle. Hemoglobin S results in red blood cells of a different shape, ones that looks C-shaped like a crescents or a "sickle," hence the disease name. The picture below shows a normal red blood cell on the left and a sickle-cell on the right:

This is a situation where looks really do matter. Sickle-shaped red blood cells don’t survive as long as normal-shaped red blood cells. Your spleen serves as an America’s Got Talent judge for your blood, clearing out those red blood cells that don’t seem to look or perform well. Thus, the spleen keeps filtering out the sickle-shaped red blood cells, leaving your body routinely short of red blood cells, resulting in anemia.

Moreover, unlike smoother disc-shaped red blood cells, these sickle-shaped ones can struggle to get through narrow blood vessels. They can stick to the inner walls of the vessels, clump together, and clog up blood vessels, creating Los Angeles-like traffic jams that impede the flow of blood to various body parts. This can result in vaso-occlusive crises. “Vaso-” means vessel, and “occlude” means stop, shut, or close. So, “occlude your mouth” would be a way of saying, “shut you mouth,” and a vaso-occlusive crisis means an emergency situation where blood flow to a part or parts of your body is shut down or blocked.

The result is severe pain and potential organ damage since your body parts are being deprived of oxygen. Stroke, vision loss, blood clots in the lungs, and infections are just some of the life-threatening complications that may result. Until now, there haven’t been any specific ways of preventing such crises, aside from drinking plenty of fluids and avoiding situations that may be triggers such as high elevation, extreme cold, physical exhaustion, and certain drugs like acetazolamide. Vaso-occlusive crises certainly can occur despite these precautionary measures. Treatment of such crises has mainly involved giving pain medications, hydration, oxygen, and potentially blood transfusions.

The approval of Adakveo offers another much more specific possibility. It’s a monoclonal antibody that can bind and block a protein called P-selectin. P-selectin sits on the cells lining the inside walls of blood vessels and in platelets. In sickle cell disease, P-selectin can help the crescent-shaped red blood cells stick to the blood vessel walls. Thus, blocking P-selectin with Adakveo may prevent this sticking and potentially prevent vaso-occlusive crises.

Indeed, a randomized clinical trial with 198 participants showed that patients who received Adakveo had fewer health care visits for vaso-occlusive crisis each year than those who received placebo (1.63 versus 2.98 visits) and had a longer time until experiencing their first vaso-occlusive crisis during the study (1.4 versus 4.1 months). In fact, over a third (36%) of those patients being treated with Adakveo didn’t even have any vaso-occlusive crises during the study.

According to Angus Liu, writing for the industry publication FiercePharma, the wholesale acquisition cost for Adakveo will be $2,357 per vial, meaning that the expected usage of three or four vials a month would come out to $7,071 or $9,428 per month. Not exactly pocket change. But this new medication could end up saving those