Zol­gens­ma did­n't cause an in­fant death, AveX­is ex­ecs say as they spot­light long-term da­ta

Be­fore the re­cent da­ta ma­nip­u­la­tion scan­dal en­gulfed No­var­tis’ star gene ther­a­py Zol­gens­ma, the death of an in­fant in one of their Phase III tri­als threat­ened to sound safe­ty alarms about the spinal mus­cu­lar at­ro­phy treat­ment. But sci­en­tists at the AveX­is sub­sidiary now say an in­ves­ti­ga­tion has cleared that par­tic­u­lar wor­ry.

Nes­tled in a lengthy pre­sen­ta­tion of up­beat da­ta, the up­date of­fers some much-need­ed val­i­da­tion for Zol­gens­ma as ex­ecs scram­ble to re­build their cred­i­bil­i­ty with both reg­u­la­tors and the gen­er­al pub­lic.

Out of the sev­er­al stud­ies tout­ed at the Eu­ro­pean Pae­di­atric Neu­rol­o­gy So­ci­ety Con­gress, there are a few key take­aways: Some of the ear­li­est pa­tients, as old as 5, are hit­ting de­vel­op­men­tal mile­stones in a long-term fol­low-up study; treat­ing in­fants be­fore they show any symp­toms of SMA has al­lowed them to grow up in a way they oth­er­wise nev­er would have; and there’s more ev­i­dence that the gene ther­a­py pre­vents symp­to­matic pa­tients’ from wors­en­ing.

While the au­top­sy re­port find­ings didn’t fea­ture up top, AveX­is ex­ecs did take the time to ad­dress them in a call with re­porters. Af­ter the British in­fant died in the STRIVE-EU study of a se­vere res­pi­ra­to­ry in­fec­tion fol­lowed by neu­ro­log­i­cal com­pli­ca­tions, the in­ves­ti­ga­tor thought the event might be re­lat­ed to treat­ment.

“We had been con­cerned about the po­ten­tial… that Zol­gens­ma might have been caus­ing brain in­flam­ma­tion,” AveX­is chief ex­ec­u­tive Dave Lennon said, as quot­ed by Reuters. “In this case, the orig­i­nal di­ag­no­sis, and that as­so­ci­a­tion, hasn’t held true.”

Al­though Zol­gens­ma might have been re­spon­si­ble for oth­er known side ef­fects such as el­e­vat­ed en­zymes in the liv­er, low platelets and low blood pres­sure, their in­ves­ti­ga­tion found no ev­i­dence of treat­ment-re­lat­ed brain dam­age. The con­clu­sion: SMA Type 1 was the un­der­ly­ing cause for the in­fec­tion, which in turn de­prived the brain of oxy­gen and trig­gered hy­pox­ic-is­chemic brain dam­age.

Mean­while, the rest of the re­sults demon­strate the “life-chang­ing im­pact Zol­gens­ma can have on chil­dren with SMA Type 1” for fam­i­lies who nev­er ex­pect­ed their chil­dren to crawl, sit or walk, said CMO Ol­ga San­ti­a­go in a state­ment.

START, which start­ed out as a 13-pa­tient safe­ty study, is now track­ing 10 of those pa­tients with a mean age of 4.2 years for whom treat­ment was on av­er­age 3.9 years ago. All are alive and the ma­jor­i­ty (sev­en) is not re­ceiv­ing Spin­raza, Bio­gen’s SMA main­te­nance ther­a­py. Six of them do not re­quire dai­ly res­pi­ra­to­ry sup­port, and at least two are able to stand with as­sis­tance in ad­di­tion to two oth­ers who were re­port­ed to be walk­ing in­de­pen­dent­ly.

Se­ri­ous ad­verse events were re­port­ed, af­fect­ing six out of the 13 orig­i­nal pa­tients, but AveX­is main­tained that noth­ing was new.

In the SPR1NT study, pa­tients were treat­ed much younger — less than 6 weeks — as they tend to be di­ag­nosed at birth. It’s on­ly been a few months since the 23 pa­tients were dosed, but among those with two copies of SMN2, six out of 10 were able to sit with­out sup­port for at least 30 sec­onds — a co-pri­ma­ry end­point. Over­all, of the 22 be­ing eval­u­at­ed, all were alive with­out the help of per­ma­nent ven­ti­la­tion.

The fi­nal da­ta cut won’t be tak­en un­til two years af­ter treat­ment, yet these in­ter­im re­sults show why it’s crit­i­cal to di­ag­nose SMA and in­ter­vene as ear­ly as pos­si­ble, ac­cord­ing to San­ti­a­go.

A sep­a­rate Phase III glob­al tri­al dubbed STR1VE is al­so watch­ing for the 30-sec­ond sit­ting as a co-pri­ma­ry end­point. There, so far, 50% of pa­tients in the US tri­al and 6% in the EU tri­al has hit that goal — some­thing that ba­bies with SMA Type 1 would nev­er be able to do, AveX­is em­pha­sized.

The oth­er co-pri­ma­ry is event-free sur­vival as mea­sured by avoid­ance of death or per­ma­nent ven­ti­la­tion. The tri­al is sched­uled to wrap lat­er this year.

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.