Why not? Sarepta’s third Duchenne MD drug sails to accelerated approval

Amber Tong

Senior Editor

Sarep­ta may be run­ning in­to some trou­ble with its next-gen gene ther­a­py ap­proach to Duchenne mus­cu­lar dy­s­tro­phy. But when it comes to an­ti­sense oligonu­cleotides, the well-trod­den reg­u­la­to­ry path is still lead­ing straight to an ac­cel­er­at­ed ap­proval for casimersen, now chris­tened Amondys 45.

We just have to wait un­til 2024 to find out if it works.

Amondys 45’s ap­proval was un­cer­e­mo­ni­ous, com­pared to its two old­er sib­lings. There was no con­tro­ver­sy with­in the FDA over ap­prov­ing a drug based on a bio­mark­er rather than clin­i­cal ben­e­fit, set­ting up a pow­er­ful prece­dent that still haunts act­ing FDA com­mis­sion­er Janet Wood­cock as biotech in­sid­ers weighed her po­ten­tial per­ma­nent ap­point­ment; no dra­ma like the FDA is­su­ing a stun­ning re­jec­tion on­ly to re­verse its de­ci­sion and hand out an OK four months lat­er, which got more com­pli­cat­ed af­ter the scathing com­plete re­sponse let­ter was pub­lished; no anx­ious tea leaf read­ing or heat­ed ar­gu­ments from drug de­vel­op­ers and pa­tient ad­vo­cates who were tired of hav­ing cor­ti­cos­teroids as their loved ones’ on­ly (some­times ex­pen­sive) op­tion.

If any­thing, a pri­or­i­ty re­view set it up for a wide­ly ex­pect­ed green light for what an­a­lysts pre­dict will be the last prod­uct de­vel­oped on the phos­pho­ro­di­ami­date mor­pholi­no oligomer plat­form while Sarep­ta shifts fo­cus to new­er fran­chis­es.

De­spite re­cent set­backs on the reg­u­la­to­ry and da­ta fronts — in which a gene ther­a­py failed the key end­point on mus­cle func­tion — the biotech has stood firm­ly by the po­ten­tial of its ge­net­ic fix. There’s a lot at stake: Head-and-neck in a race against Pfiz­er (and to a less­er ex­tent Sol­id Bio), Sarep­ta had scored ear­ly wins in clin­i­cal tri­als and wooed Roche as a part­ner be­fore the phar­ma gi­ant beat it to a Phase III tri­al.

Per­haps low­er pro­file is the pep­tide-con­ju­gat­ed phos­pho­ro­di­ami­date mor­pholi­no oligomer, or PP­MO, plat­form. The first pro­gram, SRP-5051 for ex­on 51 mu­ta­tions, is in a Phase II tri­al coined MO­MEN­TUM with da­ta ex­pect­ed in the sec­ond quar­ter of 2021, SVB Leerink an­a­lyst Joseph Schwartz wrote:

From our re­cent con­ver­sa­tions with mgmt, it ap­pears SRPT is keen to quick­ly ad­vance SRP-5051 stat­ing Ph.2 MO­MEN­TUM’s Part B could po­ten­tial­ly be reg­is­tra­tional in the US. Fol­low­ing quick­ly be­hind SRP-5051 are PP­MOs de­signed to tar­get ex­ons 53 and 45. De­pend­ing on SRPT’s pace, it is pos­si­ble some PP­MOs could be in late-stage piv­otal tri­als or even be­yond be­fore PMO con­fir­ma­to­ry tri­als read out.

The place­bo-con­trolled con­fir­ma­to­ry tri­als are de­signed to see if an in­crease in dy­s­trophin pro­duc­tion spurred could in­deed pa­tients walk, and they take close to two years of fol­low-up. ESSENCE — the one in­volv­ing Vyondys 53 and Amondys 45 — is ex­pect­ed to con­clude in 2024. MIS51ON, test­ing Ex­ondys 51, won’t wrap un­til 2026, ac­cord­ing to a list­ing on clin­i­cal­tri­als.gov.

That gives Sarep­ta plen­ty of time to catch up and beef up its sales ef­fort. Ac­cord­ing to the biotech, around 8% of Duchenne pa­tients have a mu­ta­tion amenable to ex­on 45 skip­ping.

“Along with our oth­er ap­proved RNA ther­a­pies, we can now of­fer treat­ment op­tions for near­ly 30% of Duchenne pa­tients in the U.S,” CEO Doug In­gram said. “And our com­mit­ment to bring ther­a­pies to the great­est per­cent­age of the DMD com­mu­ni­ty as soon as pos­si­ble con­tin­ues.”

At its last quar­ter­ly up­date in 2020, Sarep­ta re­port­ed that its two Duchenne drugs on the mar­ket earned $333.2 mil­lion in the first nine months. It ex­pects Amondys 53 to bring in as much as $547 mil­lion in an­nu­al sales, ac­cord­ing to its rev­enue guid­ance.

Amondys 45 will be “priced at par­i­ty” with those two oth­er ap­proved treat­ments. Both Ex­ondys 51 and Vyondys 53 cost $1,680 for 2ml; the ac­tu­al an­nu­al price varies de­pend­ing on the pa­tient’s weight, and es­ti­mates have ranged from $300,000 to $892,000. Mean­while, Vil­tep­so — a sim­i­lar an­ti­sense oligonu­cleotide de­vel­oped by Japan’s NS Phar­ma — has a price tag of around $733,000 per year.