Sarep­ta leads off Duchenne MD gene ther­a­py study with a ‘home run’ on ef­fi­ca­cy — but can they de­liv­er in 2 years?

Sarep­ta $SRPT has leaped out in­to the front of the race to de­vel­op a once-and-done gene ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy. 

With their R&D day in full swing Tues­day, com­pa­ny ex­ecs and the se­nior re­searcher on their ground­break­ing hu­man gene ther­a­py study post­ed a first look at the promis­ing re­sults seen in three young pa­tients who re­ceived treat­ments in a small study with no con­trol which will in­volve a to­tal of 12 boys. The da­ta are very ear­ly, but the im­me­di­ate re­sponse seen in the first few months has in­spired the com­pa­ny to be­lieve that it is on the right track to get a new ther­a­py to these pa­tients in as lit­tle as two years — pro­vid­ed all the stars align in its fa­vor.

“If you were me, look­ing un­der the mi­cro­scope, you would be so amazed you wouldn’t sleep at night,” says Jer­ry Mendell, the not­ed gene ther­a­py ex­pert at Na­tion­wide Chil­dren’s Hos­pi­tal in Colum­bus, OH who is lead­ing the project.

Doug In­gram

CEO Doug In­gram called the re­sults a “home run” dur­ing a pre­view of to­day’s pre­sen­ta­tion. Look­ing over the time­line, In­gram told me that it was con­ceiv­able that they would be ready to roll with a ther­a­py in 24 months, but that would re­quire a near per­fect ex­e­cu­tion of the plan, with no nasty sur­pris­es.

That doesn’t hap­pen very of­ten in biotech. But they’re try­ing. Hard.

Baird’s Bri­an Sko­r­ney called it “amaz­ing,” and the mar­ket agreed. The stock, which has been climb­ing north steadi­ly over the past few months, rock­et­ed up 56%.

The main goal of this first hu­man study is safe­ty, but in­ves­ti­ga­tors al­so tracked how each of the first three boys in a co­hort of six boys aged 4 to 7 re­spond­ed based on some well un­der­stood bio­mark­ers. And while the num­bers rep­re­sent on­ly three pa­tients, small num­bers and ini­tial re­sults like this are key in gene ther­a­py — with the caveat that there’s a ton of ad­di­tion­al work that needs to be done to prove that the ben­e­fits are life-chang­ing for the boys and durable for years to come.

The first pic­ture looks stel­lar, eas­i­ly out­strip­ping ex­pec­ta­tions.

Here’s what Mendell has been los­ing sleep over, for good rea­sons:

• Mean gene ex­pres­sion, as mea­sured by per­cent­age of mi­cro-dy­s­trophin pos­i­tive fibers was 76.2% and the mean in­ten­si­ty of the fibers was 74.5% com­pared to nor­mal con­trol. Break­ing that down on a pa­tient-by-pa­tient ba­sis the per­cent­ages on mi­cro-dy­s­trophin ex­pres­sion in mus­cle fibers demon­strat­ed some vari­abil­i­ty, rang­ing from a low of 59% to 83%, while the per­cent­age of dy­s­trophin-pos­i­tive fibers fell in a more nar­row band of 73.5% to 78%.

• Biop­sies run by in­ves­ti­ga­tors showed a mean lev­el of mi­cro-dy­s­trophin of at least 36.5%, rang­ing up us­ing a dif­fer­ent mea­sure. 

• Lev­els of cre­a­tine ki­nase in blood — an en­zyme that leaks out of dam­aged mus­cles which is used to di­ag­nose the dis­ease — plunged by a mean of 87%.

Source: Sarep­ta

Click on the im­age to see the full-sized ver­sion

Oth­er than two cas­es of el­e­vat­ed gam­ma- glu­tamyl trans­ferase suc­cess­ful­ly treat­ed with in­creased steroids, re­searchers re­port­ed no oth­er safe­ty is­sues.

“These kids are at a point now where they wouldn’t be able to join the tri­al,” says In­gram.

Way bet­ter than any­one could have hoped for,” added Sko­r­ney. “And the CK da­ta is in­dica­tive of a clin­i­cal ef­fect, which would have been the ques­tion if all we saw was pro­tein ex­pres­sion.”

That’s good, if not great, but it al­so de­serves some per­spec­tive. Duchenne MD is a pro­gres­sive dis­ease, which slow­ly crip­ples and then kills the kids. If one of the pa­tients has de­clined to the point where they are in a wheel­chair, says Mendell, they’ll like­ly re­main in their wheel chair. No one is get­ting up and walk­ing af­ter suf­fer­ing that much dam­age to their mus­cles. But it could play a key role in main­tain­ing up­per body strength and pos­si­bly al­low them to lead a full life over a nor­mal span, or some­thing fair­ly close to that. 

The younger pa­tients would en­joy the great­est ben­e­fits, though again, that’s pro­vid­ed that the gene ther­a­py they have de­signed works for a long, long time.

The plan is to push ahead on a study that will re­cruit 12 boys for the con­trol arm, and keep check­ing each pa­tient for their re­spons­es. Af­ter a year, the pa­tients in the con­trol will move over to re­ceive the treat­ment.

In­ves­ti­ga­tors in­volved in the work pub­lished snaps of the da­ta they’re col­lect­ing, in­clud­ing the West­ern Blot re­sults. Sarep­ta and the FDA got in­to an epic don­ny­brook over the da­ta that were pre­sent­ed for their first drug eteplirsen, with heat­ed claims that much of what was of­fered was un­re­li­able at best, if not in­ten­tion­al­ly mis­lead­ing. The biotech seems de­ter­mined to avoid a re­peat of that reg­u­la­to­ry dis­as­ter, which would have killed their pitch to reg­u­la­tors — a ma­jor­i­ty of the ex­pert pan­el vot­ed against ap­proval — if Janet Wood­cock had not over­ruled the lot of them and forced an ap­proval through.

The par­ents of these Duchenne vic­tims are a force of na­ture. It was their de­mands that won over Wood­cock and a sig­nif­i­cant bunch of sup­port­ers in and around the na­tion’s capi­tol. And they will want an ef­fec­tive gene ther­a­py as fast as pos­si­ble.

So I asked In­gram if the com­pa­ny would be will­ing to pro­vide this gene ther­a­py if a fam­i­ly asked for it, as pro­vid­ed in Right to Try or as part of a com­pas­sion­ate use pro­gram. He replied that the com­pa­ny would re­main laser fo­cused on the study.

So, no.

Sarep­ta may be in the lead on a Duchenne gene ther­a­py, but it’s not alone. Pfiz­er is work­ing here,  hav­ing dosed its first pa­tient two months ago, and Sol­id Bio just got a green light from the FDA to re-start its first tri­al af­ter a se­ri­ous re­ac­tion in the first pa­tient raised con­cerns and forced a tem­po­rary halt to the study. They’ll be play­ing catch-up, look­ing for any edge to leap in front of the leader. And all the da­ta will be im­me­di­ate­ly lined up for quick com­par­isons, to see who’s got the best re­sults.

Im­age: Jer­ry Mendell. JAIN FOUN­DA­TION

Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

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Inspired by his recent experiences scrounging for space in Boston and the Bay Area, master biotech builder, investor, and global dealmaker Arie Belldegrun has organized a new venture to build a new, 250,000 square foot biopharma building in Boston’s Seaport district — home to Vertex and a number of up-and-coming biotech players.

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Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

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Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

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Norbert Bischofberger. Kronos

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