Roche and part­ner PTC Ther­a­peu­tics have bro­ken out de­tailed pos­i­tive da­ta back­ing their spinal mus­cu­lar at­ro­phy ther­a­py, which is ex­pect­ed to have a good shot at eclips­ing Spin­raza’s mar­ket lead­er­ship.

The FDA is set to make its de­ci­sion on the ther­a­py, ris­diplam, by May 24. If ap­proved — the drug is ex­pect­ed to gen­er­ate be­tween $2 bil­lion and $3 bil­lion in peak sales — and com­pete with Bio­gen’s first-to-mar­ket Spin­raza and No­var­tis’ most-ex­pen­sive-drug-in-the-world Zol­gens­ma.

On Thurs­day, the com­pa­nies re­port­ed de­tailed da­ta from the SUN­FISH tri­al, which test­ed ris­diplam against a place­bo in 180 pa­tients aged 2-25 years with type 2 and 3 SMA, a rare ge­net­ic mus­cle-wast­ing dis­ease. Most pa­tients in the tri­al were old­er, and a rel­a­tive­ly more se­vere form of the dis­ease. The main goal of the study — which was met — was the change in mo­tor func­tion af­ter one year. Roche ini­tial­ly an­nounced the pri­ma­ry end­point had been met last No­vem­ber.

The to­tal mean change in pa­tients re­ceiv­ing ris­diplam was sig­nif­i­cant­ly high­er than place­bo (1.55 point mean dif­fer­ence; p=0.0156). As ex­pect­ed, the strongest re­spons­es ver­sus place­bo were ob­served in the youngest pa­tients aged be­tween 2 and 5 years (78.1% ver­sus 52.9% achiev­ing ≥3 point in­crease).

It is hard to com­pute the clin­i­cal mean­ing­ful­ness of ris­diplam based on ab­solute 1.55 mean point re­duc­tion, even though sta­tis­ti­cal sig­nif­i­cance was hit, Sun­Trust Robin­son Humphrey an­a­lyst Robyn Kar­nauskas wrote in a note.

PTC man­age­ment has pre­vi­ous­ly sug­gest­ed that a 2-point dif­fer­ence would be clin­i­cal­ly mean­ing­ful us­ing the Mo­tor Func­tion Mea­sure scale (MFM-32) scale, but since the mean point dif­fer­ence was 1.55, clin­i­cal mean­ing­ful­ness may not be so ev­i­dent at first blush, she said.

These re­sults sup­ple­ment pos­i­tive da­ta from 41 pa­tient-FIRE­FISH study, which test­ed ris­diplam in pa­tients aged 1-7 months with type 1 SMA.

Ris­diplam is strate­gi­cal­ly po­si­tioned to have strong up­take in the type 2/3 SMA pop­u­la­tion, Cred­it Su­isse’s Mar­tin Auster wrote in a re­cent note. “While we ex­pect Zol­gens­ma to cap­ture the vast ma­jor­i­ty of the in­ci­dence Type 1/2 SMA pop­u­la­tion, we an­tic­i­pate ris­diplam will emerge as the dom­i­nant ther­a­py for old­er SMA pa­tients.”

Bio­gen se­cured the first-ever SMA ap­proval and has since been dosed in over 9,300 pa­tients. How­ev­er, com­par­ing Bio­gen’s da­ta to the Roche/PTC re­sults in SMA type 2/3 pa­tients is dif­fi­cult giv­en the pri­ma­ry end­points are dif­fer­ent in the two tri­als, in ad­di­tion to dif­fer­ent en­roll­ment cri­te­ria.

“While the im­pact of No­var­tis’ Zol­gens­ma has been rel­a­tive­ly mut­ed, we think that the like­ly ap­proval and launch of ris­diplam could im­pact Bio­gen’s Spin­raza fran­chise,” Cred­it Su­isse’s Evan Seiger­man wrote in a re­cent note. “We al­so think that Roche could price ris­diplam be­low Spin­raza to help en­cour­age use – es­pe­cial­ly in T2 or T3 pa­tients.”

Spin­raza, an an­ti­sense oligonu­cleotide, is in­ject­ed in the spine every four months fol­low­ing ini­tial load­ing dos­es. Zol­gens­ma, a gene-ther­a­py, is de­signed to be a one-shot cure, while ris­diplam is a dai­ly oral treat­ment, en­gi­neered to work by tweak­ing how the SMN2 gene is spliced, which rais­es func­tion­al SMN pro­tein lev­els in both the cen­tral ner­vous sys­tem and pe­riph­er­al tis­sues.

SMA is rare, af­fect­ing 1 per 8,000 to 10,000 peo­ple glob­al­ly, but rep­re­sents a lu­cra­tive bat­tle­ground for these drug­mak­ers. Spin­raza, launched in late 2016, car­ries a list price of $750,000 for the first year and $375,000 an­nu­al­ly there­after. Zol­gens­ma — on­ly ap­proved for pa­tients un­der the age of 2 — caused stick­er shock with its $2.1 mil­lion price tag and the in­evitable push­back from pay­ers, al­though No­var­tis has em­pha­sized that its five-year in­stall­ment plan and cu­ra­tive po­ten­tial makes it worth it.

“While there are al­ready 2 ef­fi­ca­cious prod­ucts ap­proved for SMA in the US, (Roche) man­age­ment…see a very large op­por­tu­ni­ty giv­en the con­ve­nient oral for­mu­la­tion of ris­diplam, num­ber of pa­tients not el­i­gi­ble for gene ther­a­py, and small up­front price com­pared to gene ther­a­py and oligonu­cleotide com­peti­tors,” SVB Leerink an­a­lysts wrote in a re­cent note.