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

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

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But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

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The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.

Jeff Kindler's Cen­trex­ion re­news bid to make pub­lic de­but

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The Boston based company, led by former Pfizer $PFE chief Kindler, originally contemplated a $70 million to $80 million IPO last year— but eventually postponed that strategy. On Wednesday, the company revived its bid to make a public debut in a filing with the SEC — although no pricing details were disclosed.