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.”

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Mi­rati's KRAS drug looks like the fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed response rates grater than sotorasib solo  and as part of combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Take­da scores a win for a rare type of lung can­cer, gear­ing up for a show­down with J&J

Four months after J&J’s infused drug Rybrevant scored the industry’s first win in a rare type of non-small cell lung cancer (NSCLC), Takeda is following up with an oral option for the small but desperate patient population.

The FDA granted an accelerated approval to Takeda’s oral TKI inhibitor Exkivity (mobocertinib) in metastatic NSCLC patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, the company announced on Wednesday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.