Roche/PTC edge clos­er to dis­rupt­ing mar­ket for SMA ri­vals Bio­gen and No­var­tis with more pos­i­tive da­ta

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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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