De­ci­pher­a's GIST ther­a­py ripretinib wins speedy FDA re­view — set­ting the stage for bat­tle with ri­val Blue­print

Blue­print Med­i­cines has the edge on tim­ing with its ri­val can­cer drug Ay­vak­it, but De­ci­phera Phar­ma­ceu­ti­cals is not far be­hind. On Wednes­day, the Waltham, Mass­a­chu­setts-based com­pa­ny dis­closed it had se­cured a speedy re­view for its drug ripretinib and an Au­gust de­ci­sion date.

Both pre­ci­sion ther­a­pies are de­signed to treat gas­troin­testi­nal stro­mal tu­mors (GIST) — a rare form of sar­co­ma found in the di­ges­tive sys­tem, most of­ten in the wall of the stom­ach.

Last month, Blue­print scored ac­cel­er­at­ed ap­proval for Ay­vak­it in pa­tients with un­re­sectable or metasta­t­ic GIST har­bor­ing a platelet-de­rived growth fac­tor re­cep­tor al­pha (PDGFRA) ex­on 18 mu­ta­tion, in­clud­ing PDGFRA D842V mu­ta­tions on the ba­sis of da­ta that showed an over­all re­sponse rate of 84%.

But the com­pa­ny’s ap­pli­ca­tion to mar­ket the drug in fourth-line GST pa­tients — the in­di­ca­tion De­ci­phera’s ripretinib is gun­ning for — was pushed to May 14. The FDA is ex­pect­ed to make its de­ci­sion on the De­ci­phera ther­a­py by Au­gust 13.

Ripretinib has a break­through drug des­ig­na­tion, which should speed things along at the FDA that of late has no prob­lem mov­ing ahead of sched­ule, es­pe­cial­ly when it comes to on­col­o­gy ther­a­pies for pa­tients with few op­tions.

“Ripretinib was ac­cept­ed for pri­or­i­ty re­view un­der the FDA’s RTOR pro­gram, which is an ef­fort to ex­pe­dite the ap­proval process for drugs that are deemed im­por­tant as new ther­a­pies by a more in­ter­ac­tive process be­tween the Agency and the Spon­sor,” SVB Leerink’s An­drew Berens wrote in a note. “As such, we would an­tic­i­pate that the drug will be ap­proved ahead of the Au­gust 13th ac­tion date (PDU­FA), as have oth­er drugs en­tered in this RTOR pro­gram and/or been grant­ed BTD.”

De­ci­phera wast­ed no time in an­nounc­ing a new round of fund­ing — just over 10 min­utes af­ter the PDU­FA date was un­veiled pub­licly — of­fer­ing $250 mil­lion in shares of its com­mon stock, rough­ly six months af­ter it raised $400 mil­lion on the back of large­ly pos­i­tive late-stage da­ta.

The raise may sig­nal that a buy­out — which was the re­sult in the case of tar­get­ed ther­a­py de­vel­op­ers Loxo and Ar­ray — is un­like­ly.

“In our view, many in­vestors had an­tic­i­pat­ed an ac­qui­si­tion ahead of the GIST launch, which ap­pears un­like­ly fol­low­ing this raise,” Berens said. “The com­pa­ny in­di­cates that the pro­ceeds will help fund pipeline ad­vance­ments, tri­al ex­pan­sion, and prepa­ra­tions for a com­mer­cial launch of ripretinib.”

In a ma­jor­i­ty of pa­tients with GISTs, the can­cer cells have a tweaked KIT onco­gene. This gene di­rects cells to make the KIT pro­tein, which caus­es the cells to un­con­trol­lably grow and di­vide. In some 5% to 10% of GISTs, the can­cer cells have a mu­ta­tion in the PDGFRA gene, which caus­es the cells to make too much of the PDGFRA pro­tein, ac­cord­ing to the Amer­i­can Can­cer So­ci­ety.

While ap­proved ki­nase in­hibitors con­trol cer­tain ini­ti­at­ing and drug re­sis­tance-caus­ing mu­ta­tions in KIT and PDGFRα, no ex­ist­ing ther­a­py can in­hib­it all known mu­ta­tions. De­ci­phera’s ripretinib is de­signed to thwart the full spec­trum of known mu­ta­tions in KIT and PDGFRα.

Da­ta from a 129 pa­tient late-stage study test­ing ripretinib in GIST pa­tients who had been pre­vi­ous­ly treat­ed with at least three ther­a­pies showed it im­proved pro­gres­sion-free sur­vival by 6.3 months ver­sus 1 month in the place­bo group. But the over­all re­sponse rate (ORR) was 9.4% (com­pared to 0% in the con­trol group) — not a sta­tis­ti­cal­ly sig­nif­i­cant re­sult. And al­though the tri­al was not pow­ered to un­der­take a for­mal analy­sis of over­all sur­vival with­out a suc­cess­ful hit on ORR, re­searchers had a look any­way — find­ing a pos­i­tive 15.1 months for the drug ver­sus 6.6 months for the con­trol arm. To re­coup the ORR miss, the com­pa­ny added some up­dat­ed ear­ly-stage da­ta from a sep­a­rate fol­low-up study of sec­ond- to fourth-line pa­tients.

Ripretinib is al­so be­ing test­ed as sec­ond-line ther­a­py in GIST pa­tients against Pfiz­er’s Su­tent in the late-stage IN­TRIGUE tri­al. In a sep­a­rate fil­ing on Wednes­day, the com­pa­ny said it was ex­pand­ing the sam­ple size of the study.

“The ex­pand­ed sam­ple size, the mag­ni­tude of which has not been dis­closed, is ex­pect­ed to be im­ple­ment­ed to al­low the com­pa­ny to main­tain the pow­er of the tri­al by ac­com­plish­ing the pre-spec­i­fied num­ber of events. While this ex­pla­na­tion ap­pears rea­son­able, we an­tic­i­pate that it could cause some con­cern among in­vestors…” Berens said. “We al­so be­lieve some in­vestors may ques­tion the tim­ing of the dis­clo­sure rel­a­tive to the of­fer­ing.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Isaac Veinbergs, Libra CEO

With $29M in Se­ries A, Boehringer-backed Li­bra looks to tack­le neu­rode­gen­er­a­tion through cel­lu­lar clean­ing

Can the natural process by which cells clean out toxic proteins be harnessed to create potential treatments for neurodegenerative disorders?

That’s the question Libra Therapeutics will be trying to answer, as the new biotech officially launched Wednesday morning with $29 million in Series A financing. The company has three preclinical programs at the ready, with its lead candidate targeting ALS and frontotemporal dementia. But CEO Isaac Veinbergs said he hopes to develop therapies for a wide range of diseases, including Parkinson’s, Alzheimer’s and Huntington’s.

Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Gene Wang, Immetas co-founder and CEO (file photo)

Im­metas Ther­a­peu­tics nabs $11M Se­ries A to nar­row their bis­pe­cif­ic work tar­get­ing in­flam­ma­tion in age-re­lat­ed dis­eases

How does a biotech celebrate its two-year anniversary? For Immetas Therapeutics, it’s with an $11 million Series A round and a game plan to fight age-related disease.

Co-founders Gene Wang and David Sinclair came together years ago around the idea that inflammation is the ultimate process driving age-related illnesses, including cancer. The duo launched Immetas in 2018 and packed the staff with industry experts. Wang, who says he’s always had an entrepreneurial spirit, has held lead roles at Novartis, GSK, Bristol Myers Squibb and Merck. He’s worked on blockbuster drugs like Humira, Gardasil, Varubi and Zolinza. And now, he’s channeling that spirit as CEO.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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