Disappointments in Gene Therapy, But Hope Remains

News broke this week about the death of a patient in a gene therapy trial. Sarepta Therapeutics, which is running a clinical study to evaluate its gene therapy for the rare disease known as Duchenne muscular dystrophy, announced that a 15-year-old trial participant had died. Since it was the second death in this trial, the company has pressed pause on dosing for patients with similar cases.

I began working in the genomics field in 2000, one year after the death in another gene therapy trial ­— that one was an 18-year-old patient in a study conducted at the University of Pennsylvania. The event essentially brought gene therapy trials to a halt for years. I remember hearing some people in the industry predict that gene therapies would never get another chance.

All these years later, and with CRISPR gene editing driving so many advances in how gene therapies can be designed and delivered, the gene therapy field is back. And yes, there are still devastating outcomes sometimes. But we’ve also seen tremendous successes: patients have achieved previously unimaginable recoveries after therapies for vision loss, cancer, sickle cell disease, and more.

The Sarepta trial response is telling. Unlike that death in 1999, the two recent patient deaths have not stopped the Duchenne muscular dystrophy trial from proceeding. Instead, scientists are closely examining both cases to determine the specific cause of each death. For example, the first patient had gotten an infection shortly before dying. Researchers will look for clues that might tell whether it was the therapy, the infection, or something else that actually killed the patient. In addition, the clinical trial team noted that both patients had a more severe form of dystrophy, so for now the gene therapy being tested will only be given to trial participants with milder symptoms in the hopes of avoiding another death. These on-the-fly adjustments are indicative of a more thoughtful and measured response from scientists and clinicians in a more mature industry.

Even as gene therapies become safer and more effective, though, the field as a whole faces many challenges. Unlike conventional medicines, gene therapies often have to be developed for each individual patient. That means they’re a lot more expensive, running from hundreds of thousands of dollars to single-digit millions of dollars. Those prices are unlikely to come down significantly anytime soon. For the pharmaceutical and biotech companies developing these treatments, they have to recoup their costs (and earn their sizable profits) from a therapy that might only be delivered one time to each patient. That’s very different from traditional drugs, where patients might stay on the same treatment for decades, making a lower cost per dose more palatable to drug developers. The sky-high prices of gene therapies can also make insurance companies more reluctant to cover them, forcing patients and their families to go through extensive pre-approval processes.

On the logistics front, gene therapies are more complicated to work with than traditional medications. They require very specific storage conditions and trained professionals to administer them. In some cases, hospitals may have to go through complex certification procedures just to be allowed to deliver these therapies within their facilities.

There is much to sort out before gene therapies become more commonplace in medicine. But even with the latest tragic news, I’m confident that the field is more resilient than it once was, and that the benefits of gene therapies will ultimately be available to many more patients.