

A decades-old scientific technology that targets disease at its genetic root has come of age. New startups are pouring into the space — and becoming major acquisition targets.

Top executives from Spark Therapeutics, Bluebird Bio, and AveXis spoke on Wednesday about the challenges they faced to become three of the most prominent biotechs in the space, as part of the Gene Therapy for Rare Disorders conference in Boston.

Spark was acquired by the Swiss drug giant Roche earlier this year for nearly $5 billion. Another large Swiss drugmaker, Novartis, bought AveXis last year for nearly $9 billion.

The field has faced serious, long-term challenges around patient safety to get where it is today, and executives quickly pointed to that issue.

Gene therapies are incredibly complex medicines, and startups can't make assumptions about how their products will work based on how other similar therapies work, or even on how they do when tested on animals like mice or monkeys, many of the experts said.

"You really have to know your own product," said Katherine High, Spark Therapeutics' cofounder, president, and chief scientific officer.

Read: Bill Gates is worried about gene editing worsening inequality. Now a top ethicist is raising new red flags.

Avoiding a potentially deadly immune-system response

Gene therapies often involve taking a patient's cells and making a change at the genetic level to target the source of their disease.

Because of this, though, they can trigger a harmful — and possibly deadly — response from the patient's immune system, which fights disease by recognizing foreign substances in the body.


Scientists test experimental therapies on non-humans first, but those models haven't always predicted how human bodies will respond, said High and Brian Kaspar, AveXis' chief scientific officer.

"I think we were all surprised" by that, High said, adding that the issue most likely also posed challenges for the scientists who developed organ transplants, which similarly trigger a life-threatening immune response in the body.

AveXis confronted this by working hard to understand how its products did in each type of animal model, Kaspar said.

"Many people do a mouse study and essentially wave their hands at human models," he said. But AveXis goes "through the same process each and every time, on each and every program."
