FDA mo­tions Al­ny­lam's lumasir­an in­to a PhI­II short track, set­ting up a shot at an OK in '20

Al­ny­lam $AL­NY may be go­ing so­lo on the de­vel­op­ment of rare dis­ease drug lumasir­an af­ter Sanofi took a pass on its op­tion, but the FDA has come through with a ma­jor as­sist. The com­pa­ny an­nounced to­day that reg­u­la­tors have agreed on a Phase III study de­sign that would ac­cel­er­ate — should all go well — its jour­ney to ap­proval.

For the tri­al de­signed to test lumasir­an in the ul­tra-rare pri­ma­ry hy­per­ox­aluria type 1 (PH1), the new­ly reached align­ment al­lows Al­ny­lam to adopt a pri­ma­ry end­point based on a bio­mark­er: the re­duc­tion of uri­nary ox­alate at six months. The FDA has al­so sanc­tioned a study size of around 25 pa­tients with PH1.

Pritesh Gand­hi

The use of a bio­mark­er spot­lights the FDA’s will­ing­ness to let drug­mak­ers shoot for faster OKs, rather than forc­ing them to wait for da­ta on dis­ease pathol­o­gy (Al­ny­lam notes the bio­mark­er is “di­rect­ly linked to the patho­phys­i­ol­o­gy of PH1 and known to be well cor­re­lat­ed with dis­ease pro­gres­sion”).

The tri­al de­sign pact with the agency al­so marks an ad­vance for the late-stage pipeline at Al­ny­lam as it waits for an ex­pect­ed ap­proval of patisir­an, which will launch their first com­mer­cial op­er­a­tions in RNAi. This biotech has been through all the ups and downs of­ten seen with any new ap­proach to drug de­vel­op­ment. And it’s poised for some ma­jor changes.

With the study de­sign ham­mered out, Al­ny­lam ex­pects to start the PhI­II study in mid-2018, re­port topline re­sults in 2019 and, if pos­i­tive, sub­mit an NDA in ear­ly 2020.

“We are very pleased with the FDA’s shared sense of ur­gency to eval­u­ate the ef­fi­ca­cy and safe­ty of lumasir­an as a po­ten­tial ther­a­peu­tic op­tion for pa­tients as rapid­ly as pos­si­ble,” said Pritesh Gand­hi, gen­er­al man­ag­er of the lumasir­an pro­gram, in a state­ment.

Al­ny­lam is cur­rent­ly con­duct­ing a Phase I/II Part B study in 20 pa­tients. Pre­lim­i­nary re­sults, an­nounced last year, sug­gest that lumasir­an led to a mean max­i­mal re­duc­tion in uri­nary ox­alate of 66% in an un­blind­ed group of four pa­tients, and all of them achieved uri­nary ox­alate lev­els at or near the nor­mal range. Lumasir­an, an RNAi ther­a­peu­tic, is de­signed to “re­duce the he­pat­ic lev­els of the [gly­co­late ox­i­dase] en­zyme, there­by de­plet­ing the sub­strate nec­es­sary for ox­alate pro­duc­tion.” It was grant­ed a break­through ther­a­py des­ig­na­tion in March.

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Vas Narasimhan. Getty Images

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David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The researcher behind base-editing is out with what some scientists are hailing as the biggest advancement in CRISPR technology since that 2016 breakthrough: “prime editing.” The new molecular gadget is capable of erasing any base pair and stenciling in another and cutting or adding long segments of DNA without breaking both strands of the helix.

David Liu, base editing pioneer and founder of Beam Therapeutics, published the findings in Nature alongside Andrew Anzalone. They estimated that the breakthrough “in principle” puts 89% of human diseases in purview — although experts cautioned that human therapies were a long way off.

Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

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HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

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Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.

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

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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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