Weeks af­ter FDA de­lay, Roche, PTC un­veil an­oth­er batch of pos­i­tive ris­diplam da­ta in se­vere SMA pa­tients

While the FDA has de­cid­ed it needs an­oth­er quar­ter to re­view Roche and PTC Ther­a­peu­tics’ oral SMA ther­a­py, its mak­ers are re­port­ing a steady drum­beat of new pos­i­tive da­ta. On Tues­day, the com­pa­nies un­veiled one-year da­ta in pa­tients with the most se­vere form of the dis­ease from a key tri­al.

The FDA is set to make its de­ci­sion on the ther­a­py, ris­diplam, by Au­gust. It is ex­pect­ed to com­pete with Bio­gen’s Spin­raza and No­var­tis’ Zol­gens­ma.

The da­ta were from Part 2 of the FIRE­FISH tri­al eval­u­at­ing ris­diplam in 41 in­fants aged 1 – 7 months old with symp­to­matic type 1 SMA. The study met the main goal — with 29% of in­fants sit­ting with­out sup­port for five sec­onds by month 12. Typ­i­cal­ly, no in­fants hit this mile­stone in the nat­ur­al his­to­ry of type 1 SMA.

Two piv­otal stud­ies con­sti­tute ris­diplam’s mar­ket­ing ap­pli­ca­tion. FIRE­FISH is an open-la­bel tri­al in in­fants with type 1 SMA, while SUN­FISH is place­bo-con­trolled and re­cruit­ed pa­tients aged 2 to 25 years with types 2 or 3 SMA. Both con­tain two parts: The first por­tion is used to de­ter­mine the op­ti­mal dose and as­sess the safe­ty, while the lat­ter is em­ployed to con­firm ef­fi­ca­cy.

Da­ta from FIRE­FISH Part 2 al­so showed 18 in­fants were able to hold their head up­right, 13 were able to roll to the side and 2 in­fants were able to stand with sup­port. In an ex­plorato­ry end­point, 95% of in­fants who were alive at 12 months (36/38) main­tained the abil­i­ty to swal­low and 89% (34/38) were able to feed oral­ly.

The drug’s safe­ty pro­file was con­sis­tent with pre­vi­ous stud­ies.

“We be­lieve that this ef­fi­ca­cy com­pares fa­vor­ably to the da­ta from Bio­gen’s EN­DEAR study of Spin­raza in Type 1 SMA, which showed that ~84% were alive af­ter 1 year of treat­ment and the event free sur­vival rate was ~55%,” Baird an­a­lyst Bri­an Sko­r­ney wrote in a note.

“While cross-tri­al com­par­isons are al­ways dif­fi­cult, we be­lieve that the strong da­ta Part 2 of the FIRE­FISH study of ris­diplam should lead to rapid up­take of this med­ica­tion once it is ap­proved, which would come at the detri­ment of Spin­raza as pa­tients are like­ly to switch to the more ef­fi­ca­cious med­ica­tion.”

Bio­gen’s Spin­raza, an an­ti­sense oligonu­cleotide, is in­ject­ed in the spine every four months fol­low­ing ini­tial load­ing dos­es. No­var­tis’ 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.

With Roche’s plan to make ris­diplam cheap­er than Spin­raza, the ap­peal of oral ad­min­is­tra­tion could make the drug an even big­ger threat to the Spin­raza fran­chise — which gen­er­at­ed near­ly $2.1 bil­lion last year — com­pared to the world’s most ex­pen­sive ther­a­py, Zol­gens­ma.

“Giv­en the dy­nam­ics sur­round­ing COVID-19, and the an­tic­i­pat­ed shift to­ward telemed­i­cine and min­i­miz­ing in-per­son in­ter­ac­tion with health­care providers, we be­lieve the com­pet­i­tive ad­van­tage of be­ing an oral ther­a­py that can be giv­en at home will be even more pro­nounced and could lead to the rapid up­take of ris­diplam should the med­ica­tion gain ap­proval by the Au­gust 24th PDU­FA,” Sko­r­ney added.

Ear­li­er this month, the FDA said it need­ed an­oth­er three months to re­view ad­di­tion­al da­ta on the drug sub­mit­ted by its mak­ers.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,000+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.

Gilead bol­sters its case for block­buster hope­ful fil­go­tinib as FDA pon­ders its de­ci­sion

Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.

Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,000+ biopharma pros reading Endpoints daily — and it's free.