Spark Therapeutics’ Luxturna advisory committee vote sets gene therapy landmark

After decades of research, a gene therapy to correct a specific genetic mutation is on the brink of being approved by the FDA.

Spark Therapeutics’ Luxturna for an inherited form of blindness was unanimously backed by an advisory committee yesterday, despite questions from agency reviewers about the clinical endpoints used in the biotech’s pivotal trial and safety, and the FDA will now decide whether to greenlight it by Jan. 12.

The 16 members of the panel were all persuaded by the data for Luxturna (voretigene neparvovec), a one-shot treatment for a currently untreatable condition called biallelic RPE65-mediated inherited retinal dystrophy (IRD) that affects around 3,500 individuals in the U.S. and Europe. Impassioned testimony from people treated with the therapy also played its part.

In the primary phase 3 trial used to back the application for Luxturna, 93% of the participants showed some improvement in their functional vision as measured by their ability to navigate obstacles in low light—a measured known as the bilateral multiluminance mobility test (MLMT).

People with biallelic RPE65-mediated IRD are born with poor vision and typically go on to lose their sight completely. Those treated in Spark’s study showed functional improvements at 30 days—the therapy can’t restore normal sight—and that was maintained out to one year and in one case out to four years after dosing.

Patients described what that level of improvement meant to their daily lives, for example allowing them to read facial expressions, recognize colors and go out at night.

Albert Maguire, M.D., of the Scheie Eye Institute, who led the trial, said: "As a practicing physician who often speaks with patients and families living with IRDs, these conversations have been, up to now, frustrating in that there has been nothing to offer. 

"Today’s advisory committee vote is an important step closer to the day that discussion can include potentially treating the blindness caused by their IRD."

Philadelphia-based Spark said the positive vote "moves us closer to bringing this investigational adeno-associated viral (AAV) vector gene therapy to patients," while analysts at Jefferies said approval by the FDA would be a "watershed moment" for the entire gene therapy field.

With approval looking likely, the conversation has swiftly switched to pricing, but the biotech isn’t revealing its plans on that just yet, saying it will do so once FDA has delivered its verdict. Some analysts have suggested, however, that a price tag of $1 million could be on the cards, following in the footsteps of uniQure and its Glybera for lipoprotein lipase deficiency (LPLD), which was the first gene therapy to be approved in Europe.

uniQure’s therapy was a commercial disaster, however, and was withdrawn from the market earlier this year due to lack of demand. GlaxoSmithKline was the second company to get the OK for a gene therapy in Europe and priced its product—Strimvelis for severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency—at a more modest $650,000 a year, but hasn’t said much about takeup.

The closest comparator for Luxturna to date is Novartis’ CAR-T therapy Kymriah (tisagenlecleucel), which has a one-off treatment price of $475,000 but addresses a larger patient population, and most observers seem to expect Luxturna to come in a little higher than that.

The panel vote is just one of a number of positive developments for Spark of late, coming after encouraging data for its hemophilia A and Pfizer-partnered hemophilia B programs and the filing of Luxturna in Europe.

Shares in the company were up nearly 8% in after-hours trading and have been rising steadily over the last six months on expectations that Luxturna was heading for approval.