By: Patricia Oneal, M.D., and Rosanna Setse, M.D., M.P.H., Ph.D.
The medical definition of sickle cell disease – a group of inherited red blood cell disorders caused by abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in red blood cells – does not come close to describing the condition from the patient’s perspective. Sickle cell disorders have devastating effects on patients and their families. Patients often experience recurrent episodes of excruciating pain, or sickle cell crisis, debilitating fatigue, infections, cognitive disorders, strokes, a life-threatening condition called acute chest syndrome, and damage to their vital organs, tissues, and bones. In some patients, the disease may trigger frequent and very painful sickle cell crises that require hospitalization. In others, it may cause less frequent and milder attacks. Although mortality during childhood has improved progressively, the life expectancy among individuals with sickle cell disease in the United States is on average 30 years less than the general population.
Sickle cell is a rare disease–but it’s not so rare if you are part of a certain population. According to the Centers for Disease Control and Prevention, about 1 of every 365 African-Americans and about 1 out of every 16,300 Hispanic-Americans are born with sickle cell disease. In addition, more than 2 million people carry the sickle cell gene that enables them to possibly pass the disease on to their children. Today, bone marrow transplantation offers the only potential cure for this disorder; but finding a donor is difficult and the procedure has serious risk.
As September — Sickle Cell Awareness Month — comes to a close, we take this opportunity to reflect on how much must be done to help patients in need and educate others on sickle cell disease — and also to recognize progress and hope for a better future.
In July, FDA approved Endari (L-glutamine oral powder) to reduce the severe complications from the blood disorder in patients age 5 years and older. Endari is only the second FDA-approved treatment for this disorder and the first since hydroxyurea was approved nearly 20 years ago. Studies showed that patients taking Endari experienced fewer trips to the emergency room and fewer hospitalizations for sickle cell pain than those given a placebo. They also had fewer occurrences of acute chest syndrome. Common side effects include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain, and chest pain.
FDA works with all interested in improving the lives of patients with sickle cell disease. In February 2014, we held the first ever federal meeting with patients as part of our Patient Focused Drug Development program. A highlight was learning what symptoms bothered patients the most in their daily lives – the sort of information that can help inform the development and use of patient reported outcomes. And for the past several years, clinical review staff has organized meetings to facilitate drug development in sickle cell disease. During these events, academic researchers, clinicians and FDA engaged in an interactive discussion on trial design, potential endpoints, and patient reported outcomes.
Sickle cell disease describes a group of inherited red blood cell disorders caused by abnormal hemoglobin, the protein that carries oxygen throughout the body. Normal hemoglobin moves easily through blood vessels, but sickle hemoglobin can be crescent or sickle shaped, which causes it to stick on vessel walls, blocking or stopping the flow of blood.
It is not entirely clear why progress in developing treatments for sickle cell disease has been slow. One challenge has been the multi-faceted nature of sickle cell disease as well as difficulty in defining biochemical endpoints and targets of clinical benefit in clinical trials. But there is hope.
Since 2010, we have seen a rise in the number of industry meetings, clinical trial development and investigational new drug (IND) submissions for sickle cell disease (required when companies want to conduct clinical trials of an investigational new drug), which may qualify for an expedited approval program known as Fast Track. Patient-reported outcome measures are being incorporated into clinical trials for new products. Currently 143 clinical trials (on Clinicaltrials.gov) are recruiting patients studying drug interventions, gene therapy, behavioral treatment and diagnostic testing in both adults and children.
While we at the Center for Drug Evaluation and Research work to encourage drug development, other efforts are underway to make bone marrow transplantation accessible to more patients as well as utilizing gene editing which can provide a permanent cure for sickle cell disease by correcting the sickle mutation in the stem cells.
We know there is much more work to be done, but FDA is proud to say during this Sickle Cell Awareness Month, that we are part of a dynamic team and remain committed to promoting the development of safe and effective treatments for this blood disorder.
Patricia Oneal, M.D., is a Medical Officer in the Division of Hematology Products at FDA’s Center for Drug Evaluation and Research.
Rosanna Setse, M.D., M.P.H., Ph.D., is a Medical Officer in the Office of Hematology & Oncology Products at FDA’s Center for Drug Evaluation and Research.
For more information, please visit: The FDA Encourages New Treatments for Sickle Cell Disease