New Zol­gens­ma da­ta sug­gest com­pa­ra­ble ef­fi­ca­cy to Spin­raza — an­a­lysts

As No­var­tis awaits the FDA de­ci­sion on its spinal mus­cu­lar at­ro­phy (SMA) gene-ther­a­py, Zol­gens­ma, the com­pa­ny that de­vel­oped the treat­ment for the rare, dead­ly in­her­it­ed dis­or­der, AveX­is, pre­sent­ed da­ta snap­shots from on­go­ing tri­als on Sun­day, prompt­ing an­a­lysts to sug­gest that the one-shot ther­a­py was look­ing com­pa­ra­ble to Bio­gen’s ap­proved Spin­raza.

In the on­go­ing late-stage STR1VE study, de­signed to eval­u­ate the ef­fi­ca­cy and safe­ty of a one-time IV in­fu­sion of Zol­gens­ma in pa­tients with SMA Type 1 who are <6 months of age, da­ta showed pa­tients con­tin­ued to show event-free sur­vival well above nor­mal his­tor­i­cal con­trols, AveX­is sug­gest­ed at the Amer­i­can Acad­e­my of Neu­rol­o­gy an­nu­al meet­ing.

SMA caus­es mus­cle weak­ness and pro­gres­sive loss of move­ment, trig­gered by a ge­net­ic de­te­ri­o­ra­tion in the nerve cells con­nect­ing the brain and spinal cord to the body’s mus­cles. Ba­bies with type 1 rarely sur­vive be­yond the first few years of life, while most chil­dren with type 2 sur­vive in­to adult­hood. Types 3 and 4 don’t usu­al­ly af­fect life ex­pectan­cy. The Swiss drug­mak­er has sug­gest­ed a price of $4 -$5 mil­lion for Zol­gens­ma, which it ac­quired via its $8.7 bil­lion takeover of AveX­is.

An­oth­er sig­nif­i­cant up­date was the snap­shot from the STRONG study, which is eval­u­at­ing the in­trathe­cal de­liv­ery of Zol­gens­ma in pa­tients with SMA Type 2. Pa­tients were strat­i­fied in­to two groups based on age at time of dos­ing: pa­tients who are ≥6 months but <24 months, and pa­tients who are ≥24 months but <60 months. The pri­ma­ry ef­fi­ca­cy out­come for pa­tients in the first group is the abil­i­ty to stand with­out sup­port ≥3 sec­onds; the main goal for the sec­ond group is a change in Ham­mer­smith Func­tion­al Mo­tor Scale-Ex­pand­ed (HFMSE) score from base­line. Since dos­ing, 22 mo­tor mile­stones in 10 pa­tients have been achieved across Dose A and Dose B, in­clud­ing two pa­tients who gained the abil­i­ty to stand in­de­pen­dent­ly, one of whom went on to walk alone, and one pa­tient who gained the abil­i­ty to walk with as­sis­tance. The me­di­an du­ra­tion of fol­low-up was 6.5 months and all 30 pa­tients are alive.

“The av­er­age age at en­roll­ment in STRONG was 17 months…these re­sults are chal­leng­ing to in­ter­pret or com­pare with the Spin­raza da­ta since the Bio­gen/Io­n­is study en­rolled pa­tients who were slight­ly old­er (3 years at base­line). Thus, we be­lieve the most com­pa­ra­ble dat­a­point is ef­fi­ca­cy on the HFMSE, which was the pri­ma­ry end­point in Bio­gen/Io­n­is’ Spin­raza tri­al. On this mea­sure, AVXS-101 pro­duced a mean 4.2 point im­prove­ment at a me­di­an fol­low up time of 7.5 months; by com­par­i­son, Spin­raza gen­er­at­ed a ~3 point im­prove­ment at 9 months in the Phase III CHER­ISH study. The mag­ni­tude of these im­prove­ments are ob­vi­ous­ly very close to one an­oth­er, and when we think about STRONG/CHER­ISH de­signs and the re­cruit­ed tri­al pop­u­la­tions, the bal­ance of con­found­ing vari­ables prob­a­bly fa­vors the STRONG study a lit­tle, un­der­ly­ing our con­clu­sion that the ef­fi­ca­cy of gene ther­a­py and Spin­raza are prob­a­bly pret­ty sim­i­lar,” Stifel an­a­lysts wrote in a note.

Ever­core ISI’s Umer Raf­fat sug­gest­ed that in the sec­ond group, al­though Zol­gens­ma ap­pears to kick in faster, both the gene-ther­a­py and Bio­gen’s $BI­IB Spin­raza plateau at the same. But, there is one cru­cial caveat — the pa­tients in AveX­is tri­al seemed to have low­er HFMSE scores to be­gin with, he wrote.

Over­all, no treat­ment-emer­gent deaths have been pre­sent­ed in the new da­ta, he not­ed. Rough­ly two weeks ago, AveX­is dis­closed that one of the in­fants in the STR1VE-EU study died from an in­fec­tion, and au­thor­i­ties are in­ves­ti­gat­ing whether Zol­gens­ma played a role in the death. Al­though reg­u­la­to­ry bod­ies are ex­pect­ed to be ac­com­mo­dat­ing for safe­ty is­sues when it comes to a po­ten­tial once-and-done treat­ment for the lethal dis­ease, com­pe­ti­tion ab­sent these safe­ty con­cerns could cer­tain­ly tem­per adop­tion.

The AveX­is da­ta “looks com­pet­i­tive and like a vi­able op­tion for pa­tients, in­clud­ing new in­trathe­cal dos­ing for Type 2, etc, and be­yond just in­fants (where gene ther­a­py is most com­pet­i­tive to start). We think FDA ap­proval and a fair­ly ‘broad la­bel’ could be com­ing for No­var­tis as soon as this week. Our doc sur­vey sug­gests more than 1/3 of pa­tients could opt for this; hence, Bio­gen es­ti­mates may be too high for Spin­raza,” Jef­feries an­a­lysts wrote in a note.

PTC Ther­a­peu­tics $PTCT and Roche’s oral SMA ther­a­py, ris­diplam, will like­ly be tak­en to the FDA for re­view  lat­er this year for a broad pop­u­la­tion, and could be on the mar­ket by the end of 2020, they added.

“Bot­tom line — we could see a 1/3, 1/3, 1/3 split of mar­ket over time,” Jef­feries an­a­lysts said. Doc­tors sug­gest gene ther­a­pies “could be 30-33% share of new SMA Type I-III pa­tients over time. An es­ti­mat­ed 20-25% could look to switch from Spin­raza to gene ther­a­py (de­pends on weight of pa­tient). 2) Sim­i­lar­ly, docs sug­gest 1/3 share for oral ris­diplam, too, af­ter 3-5 years; 3) Com­men­tary by docs sug­gests an even split of opin­ions on the mar­ket as well — from oral pills ‘very ap­peal­ing’ and ‘game chang­er’ and ‘es­pe­cial­ly at­trac­tive for teens/adults’ to oth­er ther­a­pies need more da­ta and like­ly com­bo,” cit­ing their sur­vey.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Covid-19 roundup: J&J be­gins piv­otal Phase III tri­al for vac­cine; Con­tro­ver­sial hu­man chal­lenge tri­als to be­gin in Lon­don — re­port

Johnson & Johnson announced it’s beginning a pivotal Phase III trial for its Covid-19 candidate, JNJ-78436735 — the first single-dose vaccine in this stage.

The Phase III trial, dubbed ENSEMBLE, will enroll 60,000 patients worldwide, making it the largest Phase III study of a Covid-19 vaccine to date. J&J said the candidate achieved positive interim results in a Phase I/IIa study, which will be published “imminently.” There’s a possibility that the first batches will be ready for potential emergency use in early 2021, according to the company.

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Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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