Sarep­ta posts ear­ly, rosy gene ther­a­py da­ta for limb gir­dle mus­cu­lar dy­s­tro­phy — fu­el­ing $165M buy­out of part­ner

Sarep­ta Ther­a­peu­tics $SRPT has re­vealed a promis­ing, ear­ly snap­shot of re­sults for its sec­ond gene ther­a­py pro­gram in pa­tients with a pro­gres­sive mus­cle de­gen­er­a­tive dis­or­der — months af­ter re­port­ing en­cour­ag­ing da­ta for its Duchenne gene ther­a­py, as the com­pa­ny for­ti­fies its sta­tus as a bonafide gene ther­a­py play­er. And the re­sults in­spired a $165 mil­lion buy­out.

Doug In­gram

On Wednes­day, Sarep­ta di­vulged da­ta from three pa­tients in the first co­hort of an open-la­bel Phase I/II study test­ing the use of an ex­per­i­men­tal gene ther­a­py — MYO-101 — in limb gir­dle mus­cu­lar dy­s­tro­phy (LGMD), a group of rare pro­gres­sive ge­net­ic dis­or­ders char­ac­ter­ized by wast­ing and weak­ness of the vol­un­tary mus­cles of the hip and shoul­der ar­eas (limb-gir­dle area) that have no ap­proved treat­ments.

The ther­a­py — which in­fus­es the cor­rec­tive gene us­ing a virus as a ve­hi­cle — is de­signed to treat LGMD2E, al­so known as be­ta-sarco­gly­canopa­thy, a se­vere form of LGMD char­ac­ter­ized by pro­gres­sive mus­cle fiber loss, in­flam­ma­tion and mus­cle fiber re­place­ment with fat and fi­brot­ic tis­sue.

MYO-101, along with four oth­er ex­per­i­men­tal LGMD gene ther­a­pies, was in-li­censed for $60 mil­lion by Sarep­ta last May from a pri­vate biotech called My­onexus (which burst on­to the scene with $2.5 mil­lion in seed fund­ing in 2017). On Wednes­day, Sarep­ta said it had ex­er­cised its op­tion to buy the com­pa­ny for $165 mil­lion.

Tri­al da­ta on the three pa­tients showed the ther­a­py re­ju­ve­nat­ed the pro­duc­tion, by an av­er­age of 51%, of be­ta-sarco­gly­can, the pro­tein re­quired for mus­cle func­tion that is miss­ing in this pa­tient pop­u­la­tion. The da­ta were mea­sured fol­low­ing a mus­cle biop­sy 60 days fol­low­ing in­fu­sion.

Whether the en­hanced pro­duc­tion of the be­ta-sarco­gly­can trans­lates to func­tion­al im­prove­ments re­mains to be seen, and the com­pa­ny will pro­vide those da­ta as it an­a­lyzes them at an up­com­ing med­ical meet­ing.

Cred­it Su­isse’s Mar­tin Auster pre­dict­ed that the ev­i­dence of po­ten­tial func­tion­al im­prove­ments ver­sus nat­ur­al his­to­ry da­ta would be made at the MDA con­fer­ence sched­uled for April 13 to 17.

How­ev­er, based on pre­clin­i­cal da­ta, Sarep­ta said that func­tion­al im­prove­ments are seen with more than a 20% im­prove­ment in be­ta-sarco­gly­can pro­duc­tion.

In the tri­al, one of the sec­ondary end­points was the re­duc­tion in cre­a­tine ki­nase (CK), an en­zyme found in the blood that is typ­i­cal­ly el­e­vat­ed as a re­sult of mus­cle dam­age. Ini­tial da­ta showed that MYO-101 dra­mat­i­cal­ly re­duced CK lev­els on av­er­age by 90%, Sarep­ta said.

“We think every mea­sure of ef­fect ex­ceeds ex­pec­ta­tions and like­ly puts this pro­gram on a fast track to ap­proval,” Baird’s Bri­an Sko­r­ney wrote in a note.

Un­like Duchenne pa­tients, those af­flict­ed with LGMD are typ­i­cal­ly not treat­ed with steroids as stan­dard, back­ground ther­a­py. In this tri­al, pa­tients were start­ed on steroids be­fore they were in­fused with the gene ther­a­py.

Two pa­tients were fol­lowed up af­ter 90 days had el­e­vat­ed liv­er en­zymes — an is­sue that has cropped up in oth­er gene ther­a­py tri­als such as AveX­is’ (No­var­tis) SMA pro­gram — with one deemed as a se­ri­ous ad­verse event. How­ev­er, Sarep­ta said the lofty liv­er sig­nal oc­curred when the pa­tients were ta­pered off oral steroids, and symp­toms re­solved up­on sup­ple­men­tal steroid treat­ment.

The co­hort da­ta, al­though ear­ly, have a po­ten­tial read-through to all the limb-gir­dle pro­grams, Sarep­ta CEO Doug In­gram said on a con­fer­ence call with an­a­lysts on Wednes­day. The com­pa­ny’s shares $SRPT jumped about 8% in ear­ly trad­ing.

The promise of gene ther­a­pies is in­tox­i­cat­ing as they are po­ten­tial one-shot cures for pre­vi­ous­ly un­touch­able dis­eases. In just a lit­tle over a year now, SanofiNo­var­tis and Roche have all in­vest­ed in with multi­bil­lion-dol­lar gene ther­a­py M&A deals, snap­ping up the pi­o­neers in the field. Ear­li­er this week, Roche mag­ni­fied the en­thu­si­asm with its $4.3 bil­lion bet on Spark Ther­a­peu­tics $ONCE, a com­pa­ny that has ef­fec­tive­ly helped a cat­e­go­ry of blind pa­tients see again.

“While im­me­di­ate readthrough (of the Sarep­ta da­ta) goes to LGMD2B and 2C, the promise goes be­yond LGMD. We think this is what ul­ti­mate­ly dri­ves long-term val­ue here as it makes the foun­da­tion be­hind Roche’s $4.8B Spark ac­qui­si­tion seem enor­mous­ly spec­u­la­tive and lim­it­ed in con­trast,” Sko­r­ney said.

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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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?

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrates their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk which uses the same basic ingredient as Genotropin which the pharma giant sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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Alex­ion clinch­es aHUS ap­proval for Ul­tomiris as the clock ticks on Soliris con­ver­sion

Alexion has racked up a second approval for Ultomiris, the successor therapy to Soliris, as its mainstay blockbuster therapy faces a patent review process that could drastically shorten its patent exclusivity.

The FDA OK for atypical hemolytic uremic syndrome (aHUS) on Friday was widely expected after Alexion posted a full slate of positive Phase III data in January. But regulators also flagged concerns about serious meningococcal infections, slapping a black box warning on the label and mandating a REMS.

FDA ap­proval lets Foamix set its maid­en ac­ne ther­a­py on course for US mar­ket launch

Months ago, Foamix leaned on its biggest shareholders — Perceptive Advisors and OrbiMed — to financially grease its wheels, ahead of the FDA decision date for its acne therapy. On Friday, that approval came in — and the topical formulation of the antibiotic minocycline is set for a January launch.

The therapy, Amzeeq (formerly known as FMX101), was approved to treat inflammatory lesions of non-nodular moderate-to-severe acne vulgaris in patients aged 9 and older.

Christine Bunt, Robert Langer. Verseau

Armed with Langer tech and $50M, Verseau hails new check­point drugs un­leash­ing macrophages against can­cer

The rising popularity of CD47 has propelled the “don’t-eat-me” signal to household name status in the immuno-oncology world: By blocking that protein, the theory goes, one can stop cancer cells from fooling macrophages. But just as PD-(L)1 merely represents the most fruitful of all checkpoints regulating T cells, Verseau Therapeutics is convinced that CD47 is one of many regulators one can modulate to stir up or tame the immune system.