Af­ter a PhI­II fail­ure, the FDA de­liv­ers Blue­print an ex­pect­ed CRL

Some CRLs come as lit­tle sur­prise.

This morn­ing, the FDA re­ject­ed Blue­print Med­i­cines’ ap­pli­ca­tion to have their can­cer drug Ay­vak­it (avapri­tinib) ap­proved for fourth-line gas­troin­testi­nal stro­mal tu­mors, or GIST. Al­ready, though, in late April, the drug had failed the ma­jor test for that in­di­ca­tion: A Phase III tri­al pit­ting Ay­vak­it against the al­ready-ap­proved Bay­er GIST drug, re­go­rafenib.

Pa­tients on re­go­rafenib did bet­ter than those on Ay­vak­it. Af­ter the tri­al, Blue­print said they were end­ing the pro­gram for 3rd and 4th line GIST pa­tients. An­a­lysts dis­count­ed the in­di­ca­tion from their pro­jec­tions.

“Blue­print will pro­vide the VOY­AGER da­ta to the FDA as part of the on­go­ing re­view of avapri­tinib in 4L GIST (PDU­FA May 14), though ex­pects that an ap­proval is un­like­ly,” Cowen’s Marc Frahm wrote in a note to in­vestors.

To­day’s an­nounce­ment was set up by a split de­ci­sion the FDA made in Jan­u­ary. Al­though Blue­print was fac­ing a Feb­ru­ary PDU­FA, the agency chose to ad­dress the two in­di­ca­tions ad­dressed in Blue­print’s NDA sep­a­rate­ly, han­dling one ear­ly and boot­ing the oth­er down the road.

For GIST pa­tients with a rare mu­ta­tion with PDGFRa, the FDA saw clear ben­e­fit for the drug, with Ay­vak­it show­ing an 84% re­sponse rate. But in gen­er­al fourth-line GIST, the agency want­ed more da­ta. They de­layed the dead­line to May 14, by which time the Phase III tri­al would have re­sults.

With the Phase III fail­ure al­ready out, the of­fi­cial CRL changes the fore­cast lit­tle for Blue­print, but even when the study re­sults emerged, an­a­lysts urged against pan­ic. “GIST was not the the­sis,” Frahm wrote, not­ing that Blue­print was mov­ing ahead in RET-pos­i­tive can­cers and a rare dis­ease called sys­temic mas­to­cy­to­sis, where in­vestors saw greater po­ten­tial.

In the AS­CO ab­stract dump ear­li­er this week, Blue­print re­vealed da­ta from their RET-tar­get­ed can­cer drug pralse­tinib, show­ing a few com­plete re­spons­es and al­most match­ing Eli Lil­ly’s re­cent­ly ap­proved Retev­mo on over­all re­sponse — set­ting up a po­ten­tial dual mar­ket for years.

The best promise for GIST pa­tients with­out the PDFRa mu­ta­tion now lies with De­ci­phera, which has been go­ing to head to head with Blue­print on the in­di­ca­tion for a year. The com­pa­ny’s drug, ripretinib, has earned a break­through des­ig­na­tion and a pri­or­i­ty re­view for fourth-line GIST, set­ting up a de­ci­sion in Au­gust. The drug is de­signed to tar­get not on­ly PDGFRa but the KIT mu­ta­tions that fu­el a ma­jor­i­ty of GIST tu­mors.

In a late-stage study of 129 pa­tients, the drug pro­duced a pro­gres­sion-free sur­vival of 6.6 months com­pared to 1 month in place­bo, al­though the re­sponse rate was on­ly 9.4%. A study com­par­ing its ef­fects in sec­ond-line pa­tients to the ef­fects of Pfiz­er’s Su­tent is on­go­ing.

So­cial: Shut­ter­stock

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.

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EQRx chairman Alexis Borisy and CEO Melanie Nallichieri

EQRx, CStone un­furl full lung can­cer da­ta for PD-L1 drug in what the part­ners are call­ing a first

As a self-stylized drug pricing disruptor, EQRx has high hopes for its lead PD-(L)1 to offer proof of concept for the entire business model. After touting a win back in May, the biotech is back with full data in lung cancer that could back up an approval.

Patients dosed with EQRx and CStone Pharmaceuticals’ sugemalimab posted median progression-free survival of 9 months compared with 5.8 months for patients given placebo (p=0.0026), according to full data from the Phase III GEMSTONE-301 study in Stage III non-small cell lung cancer set to be presented at this weekend’s #ESMO21.

Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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As­traZeneca touts Imfinzi im­munother­a­py com­bos for lung can­cer in push to dri­ve PD-L1 drug up­take

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an Innate’s anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.

Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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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.

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Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Herceptin has long stood as standard of care across multiple advanced cancers, but a suite of next-gen players are looking to beat the aging giant at its own game. In HER2-expressing esophageal cancer, BeiGene partner Zymeworks thinks its bispecific antibody could have the juice to get it done.

Zymeworks’ bispecific antibody zanidatamab, combined with one of two chemotherapy regimens, posted an overall response rate of 75% in patients with advanced gastroesophageal adenocarcinoma (GEA) who had not previously received a HER2-targeted cancer therapy, the Vancouver-based biotech said Thursday.