Tar­get­ing blind­ness

FDA panel en­dorses treat­ment for a rare form of child­hood blind­ness

The Washington Post - - FRONT PAGE - BY LAU­RIE MCGIN­LEY lau­rie.mcgin­ley@wash­post.com

An FDA panel en­dorses an ex­per­i­men­tal gene ther­apy for pa­tients with a rare type of hered­i­tary loss of sight.

A Food and Drug Ad­min­is­tra­tion ad­vi­sory com­mit­tee unan­i­mously en­dorsed an ex­per­i­men­tal gene ther­apy Thurs­day for pa­tients with a rare kind of hered­i­tary blind­ness, set­ting the stage for a his­toric ap­proval.

If the agency agrees with the rec­om­men­da­tion, the one-time treat­ment would be the first gene ther­apy cleared in the United States for an in­her­ited dis­or­der.

Made by Philadel­phia-based Spark Ther­a­peu­tics, the ther­apy in­volves in­ject­ing a healthy ver­sion of the RPE65 gene — re­spon­si­ble for mak­ing a pro­tein needed for sight — into the eyes of pa­tients who have de­fec­tive copies of the gene. The treat­ment does not give pa­tients per­fect vi­sion but does pro­duce sub­stan­tial im­prove­ments, re­searchers said.

The FDA has ap­proved only one treat­ment that it calls gene ther­apy — Kym­riah, which is used for child­hood leukemia. That ap­proach in­volves ex­tract­ing im­mune cells, ge­net­i­cally al­ter­ing them in the lab and re­turn­ing them to the pa­tient.

By con­trast, Lux­turna, the Spark prod­uct, rep­re­sents what is thought of as true gene ther­apy, in which a func­tional gene does the job of a de­fec­tive one. About 1,000 to 2,000 peo­ple in the United States have in­her­ited reti­nal dis­eases caused by a mu­tated RPE65 gene.

The com­pany has not pro­vided an es­ti­mated cost for the treat­ment, but it’s likely to be steep. Wall Street an­a­lysts are pre­dict­ing a price of $750,000 to $1 mil­lion for both eyes. That could fuel an al­ready heated de­bate over the ris­ing cost of phar­ma­ceu­ti­cals.

Chil­dren with the dys­func­tional gene of­ten are di­ag­nosed at an early age with dis­or­ders such as Le­ber con­gen­i­tal amau­ro­sis or re­tini­tis pig­men­tosa. They have lim­ited vi­sion that typ­i­cally gets worse over time, re­sult­ing in night blind­ness and a loss of pe­riph­eral and cen­tral vi­sion. Al­most all end up com­pletely blind.

Dur­ing an all-day com­mit­tee meet­ing Thurs­day, sev­eral young peo­ple told sto­ries about how the ex­per­i­men­tal treat­ment had trans­formed their lives, al­low­ing them, for the first time, to see stars and their par­ents’ faces, and to go out at night with friends.

A few years ago, “I was at a precipice of los­ing it all,” Kate­lyn Corey, a 24-year-old Los An­ge­les res­i­dent, told the panel. She was fall­ing far be­hind in her col­lege work as her vi­sion de­te­ri­o­rated and her world lit­er­ally dark­ened. Af­ter get­ting the gene ther­apy in 2013, “I was no longer liv­ing in a black-and-white film,” she said. “I may not have gained nor­mal vi­sion, but I gained all of my in­de­pen­dence.” She grad­u­ated from col­lege and earned a master’s de­gree in epi­demi­ol­ogy.

Corey and oth­ers who spoke Thurs­day ac­knowl­edged that their vi­sion is far from 20-20 and that it isn’t clear that the im­prove­ment will be per­ma­nent. Still, the ef­fects have lasted for four years or more, re­searchers say.

The com­mit­tee’s vote of con­fi­dence is a ma­jor ad­vance for a field that has strug­gled for decades to over­come dev­as­tat­ing set­backs. “One of the hopes of the Hu­man Genome Project was to use genes to de­velop medicines,” said Kather­ine High, pres­i­dent and head of re­search and de­vel­op­ment at Spark. “It has been much more com­plex than peo­ple imag­ined, but if we can suc­ceed, it means a lot for peo­ple with rare in­her­ited dis­eases.”

Hun­dreds of gene-ther­apy clin­i­cal tri­als are un­der­way through­out the world, in­clud­ing for he­mo­philia and Hunt­ing­ton’s dis­ease, ac­cord­ing to the Al­liance for Re­gen­er­a­tive Medicine, an in­dus­try group.

For reti­nal dis­eases alone, there are more than 18 genether­apy tri­als un­der­way, ac­cord­ing to Stephen Rose, chief re­search of­fi­cer at the Foun­da­tion Fight­ing Blind­ness. The group fi­nanced some of the ear­lier re­search for the treat­ment, whose generic name is voreti­gene nepar­vovec.

The FDA isn’t re­quired to take the rec­om­men­da­tions of its ad­vi­sory com­mit­tee, but it usu­ally does. Its dead­line for de­cid­ing on the Spark treat­ment is mid-Jan­uary.

Spark was founded in 2013 based on re­search and a sub­stan­tial in­vest­ment from Chil­dren’s Hospi­tal of Philadel­phia (CHOP). In a piv­otal trial in­volv­ing about 30 pa­tients ages 4 to 44, most pa­tients who re­ceived the treat­ment showed im­prove­ment in nav­i­gat­ing a novel maze — with ob­sta­cles and ar­rows for di­rec­tions.

The ob­sta­cle course was de­signed to mea­sure pa­tients’ “func­tional vi­sion,” or the abil­ity to han­dle daily ac­tiv­i­ties in low­light con­di­tions. The pa­tients didn’t see sta­tis­ti­cally sig­nif­i­cant gains in “vis­ual acu­ity” — that is, in read­ing an eye chart.

Dur­ing the meet­ing, re­searchers showed a video of a 6-year-old pa­tient who, be­fore get­ting the treat­ment, bumped into ob­jects on the ob­sta­cle course and was un­able to com­plete it quickly. At age 10, years af­ter be­ing treated, she was able to move through the course eas­ily in sec­onds.

Chris­tian Guardino, a 17-yearold high school se­nior from Patchogue, N.Y., was di­ag­nosed with the dis­or­der when he was less than a year old. “We lit­er­ally had to keep all the lights on,” said his mother, El­iz­a­beth. “He was go­ing com­pletely blind and he couldn’t nav­i­gate on his own.”

In 2012, Chris­tian, who tes­ti­fied at Thurs­day’s meet­ing, got the treat­ment as part of the trial at CHOP and his vi­sion im­proved im­me­di­ately. Now, his mother said, he can play sports, go out with friends at night and read books, al­beit ones with large print.

Chris­tian de­scribes the change in his life as “in­cred­i­ble.” Re­cently, he com­peted on NBC’s “Amer­ica’s Got Tal­ent,” wow­ing the judges with his pow­er­ful voice. He was es­pe­cially happy, he said, to be able to see the judges so clearly.

Jean Ben­nett, an oph­thal­mol­o­gist at the Univer­sity of Penn­syl­va­nia who has been in­volved in the de­vel­op­ment and test­ing of the gene ther­apy, said the treat­ment al­lows chil­dren to be­come much more in­de­pen­dent. “They can walk around, play sports,” she said.

“I may not have gained nor­mal vi­sion, but I gained all of my in­de­pen­dence.” Kate­lyn Corey, a 24-year-old Los An­ge­les res­i­dent who par­tic­i­pated in ex­per­i­men­tal treat­ment

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