New Sickle Cell Drugs Approved

New sickle cell drugs, Adakveo by Swiss drug company Novartis and Oxbryta by Global Drug Therapeutics, were approved by the United States Food and Drugs Administration (FDA) this November. This gives hope to many people around the world who live with sickle cell disease.

Sickle cell disease is a genetic disorder in which the haemoglobin formed is abnormal, and this causes the red blood cells to have a distinctive sickled shape. This shape causes the cells to get stuck in small blood vessels, restricting blood flow and limiting oxygen supply, leading to massive pain and organ damage. The disease is known to mostly affect people living in regions where malaria is endemic, regions like Africa. This is thought to be a selective advantage against malaria. The only known cure for the disease is bone marrow transplants.

Each year, about 300,000 infants are born with major sickle-cell disorders—including more than 200,000 cases in Africa. More than 50-80% of them die before the age of 5 years. 

Oxbryta (voxelotor) which was given accelerated approval, is an inhibitor of deoxygenated sickle haemoglobin polymerization, which is the central abnormality in sickle cell disease. “With Oxbryta, sickle cells are less likely to bind together and form the sickle shape, which can cause low haemoglobin levels due to red blood cell destruction. This therapy provides a new treatment option for patients with this serious and life-threatening condition," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. 

Oxbryta, approved as oral tablets on 25th November 2019, is the first approved treatment that directly inhibits sickle haemoglobin polymerization, the root cause of sickle cell disease. According to the president of the Sickle Cell Disease Association of America, the drug could "change the course of this disease."

The drug is for use by adults and children aged 12 and older. Its approval was based on the results of a clinical trial with 274 patients with sickle cell disease, 90 of whom received 1500 mg of Oxbryta, 92 patients received 900 mg of Oxbryta and 92 patients received a placebo. After 24 weeks of treatment, 51.1% of patients receiving Oxbryta achieved a greater than 1 g/dL increase in haemoglobin compared with 6.5% receiving placebo (P < .001).The most common side effects for patients taking voxelotor were headache, diarrhoea, abdominal pain, nausea, fatigue, rash, and fever.

Adakveo (Crizanlizumab), on the other hand, is a monoclonal antibody treatment to reduce the frequency of vaso-occlusive crisis – a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells. It is for use by patients age 16 years and older. “Adakveo is the first targeted therapy approved for sickle cell disease, specifically inhibiting selectin, a substance that contributes to cells sticking together and leads to vaso-occlusive crisis,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Vaso-occlusive crisis can be extremely painful and is a frequent reason for emergency department visits and hospitalization for patients with sickle cell disease.”

Adakveo's approval was based on the results of a randomized clinical trial enrolling 198 patients with sickle cell disease with a history of vaso-occlusive crisis, with patients receiving either Adakveo or a placebo. The patients treated with Adakveo experienced fewer health care visits for vaso-occlusive crisis annually (median annual rate of 1.63 visits), compared to patients who received a placebo (median annual rate of 2.98 visits). Additionally, 36% of patients who received Adakveo did not experience a vaso-occlusive crisis during the study, and it delayed the time that patients first experienced vaso-occlusive crisis after starting treatment from 1.4 months to 4.1 months. The common side effects of the drug were back pain, nausea, fever and joint pain. The drug was approved on 15th November 2019.

Despite the good news, there is some concern that the new drugs may be unaffordable for those who need them the most. Hydroxyurea, which has been the standard care for sickle cell patients in recent years, is taken as a capsule once daily, with 100 capsules being sold for $78, putting an individual’s annual cost for the drug at around $300. In comparison, Novartis revealed that annually, the new drug will cost between $84,852 and $113,136. This means that the drug will most likely not be affordable to many Africans, yet Africans are the most afflicted by this disease.