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Despite the Hype Over Gene Therapy, Few Drugs Are Close to Approval

There are hundreds of early clinical trials, but only a handful of late-stage ones have reached completion.
September 29, 2016

Most experts in the medical field will tell you that gene therapy has finally come of age, but the numbers tell a different story. Despite 30 years of research and a bigger pipeline than ever, only a small number of gene therapy trials have completed late-stage testing or are currently in late-stage trials.

The concept of gene therapy—replacing or adding a gene to correct a faulty, disease-causing one—was first tested in a clinical trial in 1990. That ushered in a period of enormous hype, with news headlines proclaiming a life-saving approach. Then, in 1999, came the first patient death from an experimental gene therapy. That had a chilling effect, quelling much of the initial excitement.

The chill has thawed, and today hundreds of clinical trials testing gene therapies are ongoing or recruiting. Early data from recent trials have shown incredible promise for gene therapies targeting certain genetic diseases: patients have seemingly been cured of hemophilia and rare types of inherited blindness.

But the majority of such gene therapies are in phase I trials and probably won’t reach patients for many years. According to, only five late-stage gene therapy trials—that is, phase III or IV—are actively open or recruiting patients, and another five late-stage trials have been completed. Researchers who may eventually seek approval from the U.S. Food and Drug Administration for treatments they are testing must register their clinical trials on this site.

Early clinical trials are meant to establish safety, but data from larger, late-stage trials are needed to convince regulators that drugs are effective for the intended population. Although there are only a small number of gene therapies in late-stage trials for rare diseases, similar gene technology is being used now in many immune therapy studies to alter blood cells to fight cancer. 

Data from also reveal that the five completed late-stage gene therapy trials have yet to post their results to the database, which is required by law for all trials except phase I. No gene therapy for an inherited disease has been approved by the FDA, but Europe so far has approved two.

Ronald Crystal, chairman of genetic medicine at Weill Cornell Medical College and an early leader in gene therapy, says these underwhelming numbers can be explained by the fact that most gene therapy development until recently has been done by academic researchers, who often don’t have the resources or funding to conduct large later-stage trials even if data from early trials suggest that treatments are safe and effective.

For context, Crystal contrasts gene therapy to monoclonal antibodies, engineered immune proteins that home in on specific targets. Both technologies started off with great hype in the 1980s and ’90s, but it took years to make substantial advances in either. Monoclonal-antibody therapies, though, have an estimated 134 completed late-stage trials on the books, according to And more than two dozen monoclonal antibodies have been approved by the FDA for cancer and other diseases like autoimmune disorders.

Katherine High, the cofounder, president, and chief scientific officer of gene therapy leader Spark Therapeutics, chalks it up to the sheer complexity of the technology. Spark (#9 of our “50 Smartest Companies” in 2016) was the first company to conduct a randomized controlled phase III study—the gold standard in clinical research—for a gene therapy treatment. High says the company plans to submit its most advanced candidate, RPE65, which treats a rare genetic retinal disease that causes blindness, to the FDA for approval early next year.

The companies having the most success in gene therapy right now are the ones focusing on inherited monogenic diseases, those that are caused by a mutation in one gene, says Tim Miller, president and CEO of Abeona Therapeutics. Abeona is developing a gene therapy for a rare skin disorder called recessive dystrophic epidermolysis bullosa, also known as “butterfly skin” syndrome, which is caused by a mutation in a single gene. The therapy just advanced into phase II trials.

As the field of gene therapy continues to mature, drug approvals will come. It’s widely speculated that Spark’s therapy for blindness will be the first gene therapy approved in the United States. Meanwhile, we’re likely to see other research groups try to replicate the successful gene therapies for other conditions.

But first, more of those therapies need to make it to later-stage trials. And right now, there’s plenty of room.

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