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.

Mer­ck is tak­ing the ax to its US op­er­a­tions, cut­ting 500 jobs in its lat­est re­or­ga­ni­za­tion

Merck is cutting 500 jobs in its US sales and headquarters commercial teams in its latest effort to find new ways to streamline the operation.

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Alice Shaw, Lung Cancer Foundation of America

Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

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Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Flu Virus (Source: CDC)

FDA ex­pands Xofluza ap­proval as Roche strug­gles to catch loom­ing flu mar­ket

As a potentially powerful flu season looms, so does a big test for Roche and its new flu drug, Xofluza. The Swiss giant just got a small boost in advance of that test as the FDA expanded Xofluza’s indication to include patients at high risk of developing flu-related complications.

Xofluza (baloxavir marboxil) was approved last October in the US, the first landmark flu drug approval in 20 years and a much-needed green light for a company that had watched its leading flu drug Tamiflu get eaten alive by generics. Like its predecessor, the pill offered a reduction in flu symptoms but not a cure.

EMA backs sev­en ther­a­pies, in­clud­ing Mer­ck­'s Ebo­la vac­cine

The first-ever Ebola vaccine is on the precipice of approval after the European Medicine’s Agency (EMA) backed the Merck product in this week’s roster of recommendations.

The drugmaker $MRK began developing the vaccine, christened Ervebo, during the West African outbreak that occurred between 2014 and 2016, killing more than 11,000.

The current outbreak in the Democratic Republic of Congo (DRC) has shown case fatality rates of approximately 67%, the agency estimated. Earlier this year, the WHO declared the outbreak — which so far has infected more than 3,000 people — a public health emergency of international concern.