Af­ter a tri­al flop and an un­ex­pect­ed de­tour, Sarep­ta says its gene ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy looks ready to get back on the Phase III track.

Doug In­gram

A re­view of pre­lim­i­nary safe­ty and ex­pres­sion da­ta from 11 pa­tients sug­gests that the ma­te­r­i­al man­u­fac­tured with their up­dat­ed com­mer­cial process spurred con­sis­tent pro­duc­tion of dy­s­trophin, the biotech re­port­ed, while main­tain­ing a clean side ef­fect pro­file. The study, SRP-9001-103, was the first to test Sarep­ta’s com­mer­cial grade process in pa­tients.

The plan is to take these re­sults to the FDA for a meet­ing be­fore the end of June, and kick­start its much-an­tic­i­pat­ed Phase III soon af­ter.

“We feel very very good where we are,” CEO Doug In­gram said on an in­vestor call.

In­vestors clear­ly did too, send­ing shares $SRPT up 12.60% to $84.60.

Louise Rodi­no-Kla­pac

Sarep­ta was sup­posed to go in­to Phase III ear­li­er. But in Sep­tem­ber, the FDA knocked back their plans, rais­ing con­cerns about the po­ten­cy as­says they were us­ing for the piv­otal study and com­mer­cial sup­ply. And then the last tri­al, 102, failed the func­tion­al end­point.

The com­pa­ny quick­ly re­solved the as­say is­sue as well as one of the things that In­gram said con­found­ed the 102 re­sults: an “im­prob­a­ble im­bal­ance” in the base­line char­ac­ter­is­tics of a cer­tain pa­tient co­hort. The oth­er? Ti­ter­ing vari­abil­i­ty with­in the dos­es — which is what 103 is de­signed to clean up.

More specif­i­cal­ly, Sarep­ta changed the way they mea­sured the how much AAV they were dos­ing, switch­ing from the tra­di­tion­al qPCR method to a lin­ear PCR method.

Look­ing at biop­sies at week 12, they found com­pa­ra­ble bio­mark­er re­sults — whether in terms of dy­s­trophin ex­pres­sion, dy­s­trophin pos­i­tive fibers or in­ten­si­ty — said CSO Louise Rodi­no-Kla­pac.

Count Baird an­a­lyst Bri­an Sko­r­ney in the “ex­treme­ly en­cour­aged” camp.

The con­tin­ued ab­sence of se­vere ad­verse events bodes well for Sarep­ta even as it falls be­hind Pfiz­er in ini­ti­at­ing a Phase III, he added:

By our count, this marks over 60 pa­tients who have been treat­ed with AAVrh74 to date (4 in Study 101, 41 in Study 102, 11 in Study 103, and 6 LGMD2E pa­tients), which we be­lieve makes it high­ly un­like­ly that the fact that AAVrh74-based gene ther­a­py has not re­sult­ed in com­ple­ment ac­ti­va­tion is due to ran­dom chance. While there were two SAEs in this study (1 in­creased liv­er en­zymes and 1 nau­sea/vom­it­ing) over­all we view these side ef­fects as eas­i­ly man­age­able and not life-threat­en­ing. All told, we view the ab­sence of com­ple­ment ac­ti­va­tion in Sarep­ta’s pro­gram as a key dif­fer­en­ti­at­ing fac­tor as com­pared to Pfiz­er’s and Sol­id’s AAV9-based as­sets which have been plagued with these ad­verse events.

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.