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.

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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FDA ap­proves the third NSOMD drug in 18 months as Roche/Genen­tech beefs up its port­fo­lio of drugs for neu­ro­log­i­cal dis­or­ders

There were no FDA approved treatments for neuromyelitis optica spectrum disorder at the start of 2019. Now, as of Friday, there are three.

The latest entrant to the market is the Roche/Genentech drug satralizumab after US regulators gave it the thumbs up late Friday. An IL-6 inhibitor, the drug joins Alexion’s Soliris and AstraZeneca spinout Viela Bio’s Uplizna. The annual cost of satralizumab — which will hit the market as Enspryng — will be $190,000 for 13 doses, a Genentech spokesperson said, though the first year of treatment requires 15 doses and cost about $220,000.

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Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for Covid-19 vac­cine -- shares rock­et up

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Cal­lid­i­tas bets up to $102M on a biotech buy­out, snag­ging a once-failed PBC drug

After spending years developing its oral formulation of the corticosteroid budesonide, Sweden’s Calliditas now has its sights set on the primary biliary cholangitis field.

The company will buy out France-based Genkyotex, and it’s willing to bet up to €87 million ($102 million) that Genkyotex’s failed Phase II drug, GKT831, will do better in late-stage trials.

Under the current agreement, Calliditas $CALT will initially pay €20.3 million in cash for 62.7% of Genkyotex (or €2.80 a piece for 7,236,515 shares) in early October, then circle back for the rest of Genkyotex’s shares under the same terms. If nothing changes, the whole buyout will cost Calliditas €32.3 million, plus up to  €55 million in contingent rights.

Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Stéphane Bancel speaks to President Donald Trump at the White House meeting on March 2 (AP Images)

UP­DAT­ED: Mod­er­na of­fers steep dis­count in US sup­ply deal — but still takes the crown with close to $2.5B in vac­cine con­tracts

The US pre-order for Moderna’s Covid-19 vaccine is in.

Operation Warp Speed is reserving $1.525 billion for 100 million doses of Moderna’s Phase III mRNA candidate, rounding out to about $15 per dose — including $300 million in incentive payments for timely delivery. Given that Moderna has a two-dose regimen, it’s good for vaccinating 50 million people. The US government also has the option to purchase another 400 million doses for a total of $6.6 billion, or $16.5 per dose.

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A lab technician works during research on coronavirus at Johnson & Johnson subsidiary Janssen Pharmaceutical in Beerse, Belgium, Wednesday, June 17, 2020. (Virginia Mayo/AP Images)

UP­DAT­ED: End­points News ranks all 28 play­ers in the Covid-19 vac­cine race. Here's how it stacks up to­day

(This piece was last updated on August 14. Endpoints News will continue to track the latest developments through the FDA’s marketing decisions.)

The 28 players now in or close to the clinical race to get a Covid-19 vaccine over the finish line are angling for a piece of a multibillion-dollar market. And being first — or among the leaders — will play a big role in determining just how big a piece.

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