No­var­tis’ Zol­gens­ma joins grow­ing list of med­i­cines to lose ac­cel­er­at­ed as­sess­ment sta­tus in EU

The EMA’s Com­mit­tee for Med­i­c­i­nal Prod­ucts for Hu­man Use (CHMP) re­cent­ly an­nounced its de­ci­sion to re­move No­var­tis’ spinal mus­cu­lar at­ro­phy gene ther­a­py onasemno­gene abepar­vovec from its ac­cel­er­at­ed as­sess­ment pro­gram.

CHMP did not an­nounce its rea­son­ing be­hind the de­ci­sion, which ef­fec­tive­ly means that the treat­ment, ap­proved in the US as Zol­gens­ma and launched at a price of more than $2 mil­lion, will be re­viewed in the EU in 210 days rather than the ac­cel­er­at­ed 150 days. No­var­tis con­firmed that its gene ther­a­py is now un­der stan­dard ap­proval.

A No­var­tis spokesman ex­plained to Fo­cus: “This will give the agency the time they need to re­view the ro­bust amount of da­ta we are pro­vid­ing to an­swer their ques­tions.” An AveX­is (No­var­tis ac­quired AveX­is) spokesper­son al­so told Fo­cus they are work­ing close­ly with Eu­ro­pean reg­u­la­tors and an­tic­i­pate “a po­ten­tial ap­proval in Q4 2019.”

And al­though it’s rare for CHMP to make such a de­ci­sion (on­ly six oth­er med­i­cines have lost their ac­cel­er­at­ed as­sess­ment sta­tus af­ter it was grant­ed in re­cent years), many of these re­ver­sals have come in the last two months.

This month, five med­i­cines, in­clud­ing four can­cer med­i­cines, were tak­en off the ac­cel­er­at­ed as­sess­ment track.

In ad­di­tion to Zol­gens­ma, those in­clud­ed Karyopharm’s mul­ti­ple myelo­ma treat­ment se­linex­or, which was con­tro­ver­sial­ly ap­proved in the US fol­low­ing a neg­a­tive ad­vi­so­ry com­mit­tee de­ci­sion, Stem­line Ther­a­peu­tics’ rare blood dis­ease treat­ment tagrax­o­fusp, which was ap­proved in the US as El­zon­ris last De­cem­ber and Dai­ichi Sankyo’s acute myeloid leukemia drug quizar­tinib, which was re­ject­ed by FDA in June.

Sh­iono­gi’s an­tibac­te­r­i­al ce­fide­ro­col is al­so no longer be­ing re­viewed by CHMP un­der the ac­cel­er­at­ed ap­proval pro­gram, the com­mit­tee said on 9 Ju­ly.

But a de­ci­sion by CHMP to re­move a treat­ment from an ac­cel­er­at­ed as­sess­ment is not al­ways a neg­a­tive sign. For in­stance, Bay­er’s Vi­t­rakvi (larotrec­tinib), which was tak­en out of the ac­cel­er­at­ed as­sess­ment pro­gram in June, then won a rec­om­men­da­tion for con­di­tion­al ap­proval in Ju­ly.

The oth­er two treat­ments to lose their ac­cel­er­at­ed re­views were TaiMed Bi­o­log­ics’ HIV treat­ment ibal­izum­ab, which was ap­proved by the FDA in March 2018 as Trog­a­r­zo, and lost its ac­cel­er­at­ed as­sess­ment sta­tus in the EU in June, and AMMTeK’s neona­tal di­a­betes drug Amg­lidia (gliben­clamide), which was switched at day 90 at the ap­pli­cant’s re­quest to a stan­dard re­view and was lat­er rec­om­mend­ed by CHMP for a mar­ket­ing au­tho­riza­tion in Feb­ru­ary 2018.

As far as why CHMP might de­cide that it is no longer ap­pro­pri­ate to con­duct an ac­cel­er­at­ed as­sess­ment, an EMA guide­line from 2016 points to sev­er­al sce­nar­ios.

“Ex­am­ples of such sit­u­a­tions are when ma­jor ob­jec­tions have been iden­ti­fied that can­not be han­dled in an ac­cel­er­at­ed timetable, when a longer clock-stop is re­quest­ed by the ap­pli­cant (e.g. to pre­pare for the oral ex­pla­na­tion), or when the need for GMP or GCP in­spec­tion be­comes ap­par­ent dur­ing the as­sess­ment,” the guide­line says. “Sim­i­lar­ly, in case of a neg­a­tive trend fol­low­ing the oral ex­pla­na­tion, the CHMP may de­cide to con­tin­ue the as­sess­ment un­der stan­dard as­sess­ment time­lines. The new timetable will be com­mu­ni­cat­ed to the ap­pli­cant and the rea­sons for the change to the stan­dard timetable will be sum­marised in the CHMP as­sess­ment re­port.”

An EMA of­fi­cial’s pre­sen­ta­tion in 2017 al­so shows more than a dozen oth­er med­i­cines from 2013 to 2017 that ob­tained ac­cel­er­at­ed as­sess­ments but lat­er re­vert­ed to stan­dard time­lines.

So­cial im­age: Shut­ter­stock

Ed­i­tor’s note: Up­dat­ed on 7/29 with com­ment from AveX­is and a link to the 2017 EMA pre­sen­ta­tion.

RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.


Zachary Brennan

managing editor, RAPS

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