Sickle Cell Clinical Trials: What Patients Should Know About Gene Therapy Treatments

Sickle cell disease (SCD) is an inherited blood disorder that causes red blood cells to become misshapen, leading them to get stuck in blood vessels and, ultimately, deprive tissues and organs of oxygen. The disease affects about 100,000 Americans, occurring most often in Black populations. Companies and academic institutions alike have been working towards safe and effective gene therapies for decades, and ASGCT members have been at the forefront of those discoveries. Now, the expansion of treatment options calls for more patient education around clinical trial participation.

“A flurry of interest”

Erica Esrick, MD, is an attending physician at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and the local site principal investigator (PI) of a multicenter phase II trial using stem cells to induce fetal hemoglobin in SCD patients. Dr. Esrick was also the clinical PI of a similar pilot trial, and recently presented those results at the American Society of Hematology (ASH) Annual Meeting. ASGCT Member David A. Williams, MD, chief of the division of hematology and oncology at Boston Children’s Hospital, was the sponsor of the pilot study and is the study co-chair of the phase II trial with Mark Walters, MD.

Since the pilot trial began in 2018, Dr. Esrick says, there has never been a shortage of interested patients. Researchers saw “a flurry of interest” from people who learned about gene therapy in the media or through their doctors. Once the first three adults were successfully treated in the pilot, the team opened up the trial to adolescents and then to patients younger than 13.

When speaking with prospective participants, Dr. Esrick says she’s very careful to make sure they have a clear understanding of all the risks and benefits of gene therapy, which of course need to be balanced against the risks of continuing to live with SCD. Even after learning what is known and not known about treatment, many patients are very enthusiastic.

“I want to be absolutely sure that all the risks are fully understood, because there’s such a huge unmet need and a huge level of suffering,” Dr. Esrick says. “Patients and families are desperate for something to do, which is understandable.”

A disease with a dark history

Many patients have experienced racism in clinical care, Dr. Esrick says, and there is a long and awful history of unethical treatment toward Black clinical trial participants.

Unfortunately, the overlay of racism in sickle cell care has had an enormous impact on the sickle cell community, Dr. Esrick says. The condition, first described in a 1910 paper, was identified as a disease in 1922 because researchers claimed it was unique to Black people—a position reflecting common ideologies in the medical community at that time.

It's critical that people involved in clinical trials have a solid understanding of this historical background, Dr. Esrick says. 

Cystic fibrosis is comparable to SCD in that it’s an inherited and progressive disease associated with decreased quality of life and a shortened life span. However, cystic fibrosis primarily affects white Americans. Although it impacts one-third fewer Americans, cystic fibrosis receives much more research funding per patient than SCD.

Educating patients

In order to help patients understand the nuances of treatment options, care teams should use a variety of educational resources. At Boston Children’s Hospital, those include in-house materials like explanatory animations of the complex gene therapy approaches, websites like NIH’S Cure Sickle Cell Initiative, and videos on ASGCT’s Patient Education site.

There are also many verbal conversations, especially when minors are involved, Dr. Esrick says. Medical teams encourage patients to bring their family members or friends to appointments so they can listen in.

“It’s our job to answer questions, and also to discuss the issues that we think are important to be considered,” Dr. Esrick adds. If patients are eligible for multiple trials, how should they decide which one to participate in? What is the time commitment? How long will it be until the medical teams have more information on the efficacy of each treatment option?

The fact is, Dr. Esrick says, no one can say for certain which treatment option will work or which is best for any particular person. That’s why it’s important for patients to have realistic expectations coming into treatment.

“Sometimes families and patients have generated a lot of hope and enthusiasm before hearing about some of the risks, and I feel like it’s my job to walk that back a little," Dr. Esrick says. “Not to discourage them; just to make sure there’s accurate understanding.”

An exciting future

Compared to a couple of decades ago, Dr. Esrick says, there has been a huge increase in the number of treatment options for SCD. In addition to cell and gene therapies and gene editing treatments, there have been advancements in allogeneic transplants as well as new medications.

“It’s really exciting that sickle cell is one of the earlier diseases to potentially benefit from exciting new treatments like gene therapy using lentivirus vectors and gene editing using CRISPR,” she says.

For anyone thinking about participating in an SCD trial, Dr. Esrick emphasizes the importance of learning as much as possible while maintaining an awareness of potential risks.

“Talk to your own doctor, and feel empowered to reach out to people running trials to get more information.”

To learn more about SCD trials, visit ASGCT’s Clinical Trials Finder.

Devin Rose is ASGCT's communications manager.