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.

In a sec­ond big set­back for Covid-19 an­ti­body treat­ment hopes, Re­gen­eron halts en­roll­ment for more se­vere pa­tients

Regeneron has just delivered more bad news for the hope that neutralizing antibodies could be used to treat patients with more severe forms of Covid-19.

The New York biotech said today that an independent monitoring committee recommended halting enrollment of patients who need high-flow oxygen or mechanical ventilation in one of the trials on their antibody cocktail, after finding “a potential safety signal” and “an unfavorable risk/benefit profile.” The news comes a week after the NIH scrapped a trial of Eli Lilly’s Covid-19 antibody after finding it was having little effect on an initial cohort of hospitalized patients.

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Daphne Koller, Getty

Bris­tol My­er­s' Richard Har­g­reaves pays $70M to launch a neu­rode­gen­er­a­tion al­liance with a star play­er in the ma­chine learn­ing world

Bristol Myers Squibb is turning to one of the star upstarts in the machine learning world to go back to the drawing board and come up with the disease models needed to find drugs that can work against two of the toughest targets in the neuro world.

Daphne Koller’s well-funded insitro is getting $70 million in cash and near-term milestones to use their machine learning platform to create induced pluripotent stem cell-derived disease models for ALS and frontotemporal dementia.

CEO Kenji Yasukawa (Astellas)

In ear­ly blow to Ken­ji Ya­sukawa's R&D re­vamp, Astel­las drops out of the TIG­IT race, cit­ing PhI fail­ure

Just after AstraZeneca jumped into the TIGIT race, Astellas quietly disclosed that it was leaving, dropping out of a hunt for an immunotherapy approach that has shown tantalizing promise but remains largely unproven.

Astellas revealed in their second quarter earnings today that they’ve ended development of the anti-TIGIT antibody they acquired in their up to $400 million buyout of Potenza in 2018. The Japanese pharma had been testing it in combination with Keytruda in a 300-person Phase I study on patients with advanced solid tumors. A smaller study testing the antibody alone was completed, 2 years ahead of schedule, in July.

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No­vo Nordisk qui­et­ly nabs a rare 'break­through' sta­tus in NASH for its cash cow

Earlier this month, the small French biotech Inventiva touted themselves as having won the first FDA breakthrough designation in NASH since Intercept grabbed the first one back in 2015, before the disease had become one of biotech’s hottest areas. Unbeknownst to them, though, a much larger European rival had already landed the status months prior.

Novo Nordisk, the Danish metabolic giant, disclosed in their Q3 report Friday that back in August, the FDA gave them breakthrough status for semaglutide, their blockbuster diabetes drug, in NASH, or non-alcoholic steatohepatitis. The designation sets Novo up as a leading contender in a new wave of companies developing treatments for a silent and widespread disease that, despite a series of setbacks, is still viewed by many as a huge potential market.

Patrick Soon-Shiong at the JP Morgan Healthcare Conference, Jan. 13, 2020 (David Paul Morris/Bloomberg via Getty Images)

Af­ter falling be­hind the lead­ers, dissed by some ex­perts, biotech show­man Patrick Soon-Sh­iong fi­nal­ly gets his Covid-19 vac­cine ready for a tri­al. But can it live up to the hype?

In January, when dozens of scientists rushed to start making a vaccine for the then-novel coronavirus, they were joined by an unlikely compatriot: Patrick Soon-Shiong, the billionaire doctor most famous for making big, controversial promises on cancer research.

Soon-Shiong had spent the last 4 years on his “Cancer Moonshot,” but part of his project meant buying a small Seattle biotech that specialized in making common-cold vectors, called adenoviruses, to train the immune system. The billionaire had been using those vectors for oncology, but the company had also developed vaccine candidates for H1N1, Lassa fever and other viruses. When the outbreak began, he pivoted.

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Eli Lilly CEO David Ricks (Evan Vucci/AP Images)

A p-val­ue of 0.38? NE­JM re­sults raise new ques­tions for Eli Lil­ly's vaunt­ed Covid an­ti­body

Generally, a p-value of 0.38 means your drug failed and by a fair margin. Depending on the company, the compound and the trial, it might mean the end of the program. It could trigger layoffs.

For Eli Lilly, though, it was part of the key endpoint on a trial that landed them a $1.2 billion deal with the US government to supply up to nearly 1 million Covid-19 antibodies.

So what does one make of that? Was the endpoint not so important, as Lilly maintains? Or did the US government promise a princely sum for a pedestrian drug?

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CMO Merdad Parsey (Gilead)

Gilead hits the brakes on a tri­fec­ta of mid- and late-stage stud­ies for their trou­bled fil­go­tinib pro­gram. It's up to the FDA now

Gilead $GILD execs haven’t decided exactly what to do with filgotinib in the wake of the slapdown at the FDA on their rheumatoid arthritis application, but they’re taking a time out for a slate of studies until they can gain some clarity from the agency. And without encouraging guidance, this drug could clearly be axed from the pipeline.

In their Q3 report out Wednesday afternoon, the company says researchers have “paused” a Phase III study for psoriatic arthritis along with a pair of Phase II trials for ankylosing spondylitis and uveitis. Late-stage studies for ulcerative colitis and Crohn’s are continuing, but you can see for yourself how big a hole this leaves in the inflammatory disease pipeline, with obvious implications if the company abandons filgo altogether.

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As­traZeneca sells off heart fail­ure and hy­per­ten­sion drugs to Chep­lapharm for $400M

Out with the old and in with the new: AstraZeneca is selling off two heart failure and hypertension drugs to Germany-based Cheplapharm, bagging $400 million and making way for development in other areas.

Cheplapharm paid $200 million for the European rights to Atacand (candesartan cilexetil) and Atacand Plus (candesartan cilexetil and hydrochlorothiazide) back in 2018. They’re now doubling that amount for commercial control in more than 70 countries.

News brief­ing: Ax­o­vant faces months of de­lay on lead Parkin­son's gene ther­a­py; Chi­nese CAR-T biotech nabs $100M

One of Axovant’s top gene therapy prospects for its second act is hitting a roadblock that could push its clinical timelines back by almost a year.

In an update, the biotech said it was informed about delays in CMC data and third-part fill-finish issues around mid-October by its manufacturing partner, Oxford Biomedica. Axovant has been developing a suspension-based process for the Parkinson’s drug; with that taking longer than expected, it now believes “it is unlikely that its planned randomized, sham-controlled trial of AXO-Lenti-PD will enroll patients by the end of calendar year 2021.”