Albert Bourla, AP Images

Pfiz­er re­veals de­lays across the board for its clin­i­cal gene ther­a­py pro­grams

At JP Mor­gan 2020, a year af­ter tak­ing the reins at Pfiz­er, Al­bert Bourla claimed the com­pa­ny was poised to be­come a leader in gene ther­a­py. He’s since thrown hun­dreds of mil­lions of dol­lars at those plans, in­clud­ing a $630 mil­lion deal just last month for two of Voy­ager’s AAVs.

Now, it ap­pears Phase III read­outs are fur­ther away than Bourla had hoped.

Set­backs have re­sult­ed in de­lays across all three of Pfiz­er’s clin­i­cal gene ther­a­py pro­grams, the com­pa­ny re­vealed in its Q3 re­sults on Tues­day — in­clud­ing one tri­al which was paused over safe­ty con­cerns.

Pfiz­er’s slam­ming the brakes on its Sang­amo-part­nered Phase III he­mo­phil­ia A study af­ter some pa­tients re­port­ed high lev­els of Fac­tor VI­II, an es­sen­tial blood-clot­ting pro­tein. Nor­mal Fac­tor VI­II lev­els typ­i­cal­ly range from 50% to 100%, and any­thing low­er than 50% could in­di­cate he­mo­phil­ia A. How­ev­er, lev­els above 150% are as­so­ci­at­ed with an in­creased risk of throm­bo­sis, or the for­ma­tion of clots in the blood ves­sels.

Mul­ti­ple pa­tients in Pfiz­er’s he­mo­phil­ia A tri­al had Fac­tor VI­II lev­els over 150%, though the com­pa­ny has not said how many. To date, no pa­tients have ex­pe­ri­enced throm­bot­ic events, and some are be­ing treat­ed with oral an­ti­co­ag­u­lants to re­duce the risk, Pfiz­er said.

The com­pa­ny says it has vol­un­tar­i­ly halt­ed screen­ing and dos­ing in the study — which is more than half-full — un­til it can amend the pro­to­col to pro­vide guide­lines for the man­age­ment of el­e­vat­ed Fac­tor VI­II lev­els.

This isn’t Pfiz­er’s on­ly he­mo­phil­ia set­back. Sep­a­rate­ly, the com­pa­ny said, “re­cent in­ter­ac­tions with the FDA” have led it to de­cide against con­duct­ing in­ter­im analy­ses for both its he­mo­phil­ia A and B stud­ies. In­stead, it will wait for full analy­ses based on at least 50 par­tic­i­pants in the he­mo­phil­ia A study and 40 par­tic­i­pants in the he­mo­phil­ia B study, push­ing out the time­lines for both of the pro­grams.

While Pfiz­er had been an­tic­i­pat­ing read­outs in 2022 for its he­mo­phil­ia B and A pro­grams, it is now look­ing at a Q1 2023 read­out for he­mo­phil­ia B. The com­pa­ny hasn’t pro­vid­ed a new time­line for the he­mo­phil­ia A pro­gram.

That could put Pfiz­er sig­nif­i­cant­ly be­hind its ri­val uniQure, which read out some pos­i­tive Phase III re­sults from a 54-pa­tient tri­al back in June. Over the course of a 52-week pe­ri­od, uniQure’s drug re­duced pa­tients’ an­nu­al­ized rate of bleed­ing re­quir­ing treat­ment by 80% from base­line. That tri­al was briefly put on hold in De­cem­ber fol­low­ing the di­ag­no­sis of HCC in one pa­tient, but reg­u­la­tors gave uniQure the OK to re­sume in April.

uniQure says it plans to sub­mit a BLA in the first quar­ter of next year.

Pfiz­er’s al­so ex­pect­ing a de­lay in its piv­otal DMD study, which is now ex­pect­ed to read out in 2023. The news comes af­ter safe­ty con­cerns led Pfiz­er to scale back that tri­al, cut­ting out pa­tients with cer­tain ge­net­ic mu­ta­tions.

Three cas­es of mus­cle weak­ness, two of which in­clud­ed heart in­flam­ma­tion, forced the tri­al amend­ment. In its Q3 re­sults, Pfiz­er said it’s be­lieved that an im­mune re­sponse against the mi­ni-dy­s­trophin pro­tein caused these cas­es. All pa­tients were treat­ed with high­er dos­es of steroids, and all im­proved with­in a few weeks, though some are still re­cov­er­ing.

“This type of re­ac­tion is a risk po­ten­tial­ly in­her­ent to any gene re­place­ment ther­a­py, and sim­i­lar se­vere ad­verse events re­port­ed in oth­er pro­grams sup­port the no­tion that this is a class ef­fect,” Pfiz­er said.

This isn’t the first time the DMD pro­gram has hit a road­block on its late-stage path, with the com­pa­ny re­port­ing in May that it was meet­ing head­winds from the FDA on the qual­i­ty of its po­ten­cy as­says.

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