Hope for sickle cell disease patients as FDA approves innovative gene therapies

Dr Victor Oria

January 10, 2024

On December 8, 2023, the US Food and Drug Administration approved two innovative gene therapies for sickle cell disease (SCD), a devastating illness that affects thousands of Americans and many others in the global south.

For decades, a bone marrow transplant was the only viable option for patients with SCD, a choice out of reach for most patients because a suitable donor is usually an unaffected sibling.

These two therapies, Casgevy and Lyfgenia, are the first cell-based gene therapies approved for treating SCD in patients 12 years and older. Both products are made from patients’ blood stem cells, modified, and transplanted as a one-time single-dose infusion.

Significant treatment milestone

Casgevy is the first FDA-approved gene editing therapy in patients with recurrent vaso-occlusive crises. It involves editing patients’ hematopoietic stem cells using CRISPR/Cas9 technology and transplantation into the patient, where they engraft in the bone marrow and increase the production of fetal hemoglobin (HbF).

Lyfgenia utilizes a lentiviral vector system that modifies the patient’s stem cells to produce HbAT87Q, a form of hemoglobin that functions like hemoglobin A, the normal hemoglobin found in adults without SCD. Together, these two therapies represent a significant treatment milestone for SCD patients.

Sickle cell disease is a lifelong and devastating blood disorder that affects over four million people worldwide, predominantly in Africa, the Middle East, and South East Asia.

A single mutation in the gene coding for the β-globin chain of hemoglobin causes this inherited disorder. Pathologically, it is characterized by acute pain crises, hemolytic anemia, a high risk of infections, and progressive end-organ damage.

Malaria-endemic countries

The global burden of SCD disease published in August 2023 showed that the national incidence of SCD remained relatively constant from 2000 to 2021. However, the total number of births of babies with SCD increased by 13.7 percent, primarily due to population growth in sub-Saharan Africa and Caribbean nations.

During the same period, the number of people living with SCD increased by 41.4 percent (5.56 million to 7.74 million), creating a public health burden in the global south where this disease is prevalent.

The high SCD burden is dominant in malaria-endemic countries in the Caribbean, sub-Saharan Africa, the Middle East, and India. For example, Angola, Bahrain, the Democratic Republic of Congo, Ghana, Guinea, Kenya, Niger, and Sao Tome and Principe reported a SCD incidence at birth of 1000-2000 per 100,000 live births.

Substantial hurdles and potential risks

Countries like Benin, Burkina Faso, Equatorial Guinea, Nigeria, Sierra Leone, and Togo reported over 2000 incidences per 100,000 live births. These countries accounted for 44 percent of all global SCD incidences at birth. Collectively, sub-Saharan Africa accounts for over 66 percent of global SCD cases, making it an urgent public health burden. Over 90 percent of these children die from SCD-related complications, such as severe anemia and infections, before they reach five years.

This makes SCD a significant contributor to under-five mortality in Africa. In Kenya, the situation reflects the silence and magnitude of this disease. It is prevalent in 18 counties, with high incidences reported in the Coast, Nyanza, and Western regions. The Ministry of Health estimates that about 14000 children are born in Kenya with SCD yearly. Yet most of these children die before their fifth birthday primarily because of late diagnosis, lack of access to appropriate treatment, and education gaps among healthcare providers.

As SCD is predominant in malaria-endemic regions, both conditions share three similar symptoms: jaundice, severe anemia, and splenomegaly. This is the most significant contributor to misdiagnosis in peripheral hospitals, where most patients seek medical attention.

In 2021, the Kisumu County Government launched an SCD infant screening and management center to manage the misdiagnosis problem. Kisumu is among the highest-burdened counties, with 21 out of 100 children born with SCD.

These two new therapies come with substantial hurdles and potential risks despite their approval. While the cost may be manageable for some US-based patients, most patients in the Global South may not afford them.

For instance, Vertex Pharma says it will charge 2.2 million dollars to edit a patient’s gene using Casgevy, while Bluebird will charge 3.1 million dollars per patient for its Lyfgenia therapy.

Long treatment process

Second, treatment access will be challenging as only a few medical centers have been approved to do them. Moreover, the treatment process is long and requires vigorous quality checks before the edited stem cells can be transplanted. Doctors estimate they can only treat five to ten patients annually, given the detailed technical labor required for these therapies. Third, there is limited information about the long-term unwarranted consequences of these gene therapies.

For Lyfgenia, the FDA added a boxed warning that this therapy can cause certain blood cancers. While such cases have not been reported for Casgevy, extended post-treatment monitoring is crucial to address any challenges arising after the treatment is rolled out. To date, the most commonly reported side effects from the clinical trials include abdominal pain, vomiting, mouth sores, stomatitis, low blood cell counts, and febrile neutropenia.

However, this is a historic way forward in a world with limited options. For the Global South, we must find a way of getting these therapies to our patients despite their cost.


Dr Oria (PhD) is LEAD Fellow, Prof Janine Erler Research Group, Biotech Research and Innovation Centre – University of Copenhagen, Denmark.