Thumbs Up/Thumbs Down: The FDA dam­aged it­self bad­ly with the Sarep­ta OK

End­points as­sess­es the big bio­phar­ma R&D sto­ries of the week, with a lit­tle added com­men­tary on what they mean for the in­dus­try.

  Califf’s de­ci­sion to bow to Janet Wood­cock on Sarep­ta hurts the en­tire biotech in­dus­try.

Janet Wood­cock’s de­ci­sion to over­ride the caus­tic in­ter­nal crit­i­cism of Sarep­ta’s weak and at times mis­lead­ing case for its Duchenne drug eteplirsen has dam­aged the FDA in ways that will leave a mark for years to come. Over­rul­ing her col­leagues – in­clud­ing se­nior FDA of­fi­cials — to pro­vide an ac­cel­er­at­ed ap­proval this week for this ap­pli­ca­tion sends a clear mes­sage to biotech: If you can muster enough pub­lic sup­port for a cam­paign – which in­cludes an er­ro­neous study for bait — you should pro­ceed full steam ahead. To his cred­it, FDA com­mis­sion­er Robert Califf post­ed his own re­view of the case as well as the heat­ed ob­jec­tions of two top reg­u­la­tors, in­clud­ing the cur­rent act­ing chief sci­en­tist. Not to his cred­it, Califf chose to stand down in “def­er­ence” to Wood­cock’s in­tran­si­gence, but not be­fore chid­ing Sarep­ta for pro­mot­ing a study that raised false hopes in the pa­tient com­mu­ni­ty, which swal­lowed it all hook, line and sinker. He was al­so none too hap­py that Sarep­ta stayed fo­cused on its lob­by­ing cam­paign rather than the clin­i­cal work that need­ed to be done. I sin­cere­ly hope that eteplirsen does every­thing that ad­vo­cates de­vout­ly be­lieve it does, with­out pre­sent­ing the dan­gers cit­ed for a “sci­en­tif­i­cal­ly el­e­gant place­bo.” And let’s hope pa­tients aren’t left to cov­er any of the $300,000 an­nu­al cost. Pay­ers, and ul­ti­mate­ly so­ci­ety, can and should do that now. And what hap­pens next? Does the FDA now slap back the next com­pa­ny to use sim­i­lar tac­tics, to try and reestab­lish old bound­aries? Or does it low­er its stan­dards per­ma­nent­ly, en­cour­ag­ing more large demon­stra­tions and dodgy da­ta to back weak ap­pli­ca­tions? That’s a po­si­tion the FDA should nev­er have been put in. And that is on Janet Wood­cock and Robert Califf.

 The im­muno-on­col­o­gy rev­o­lu­tion will cause lots of pain, but it will be worth it.

We are liv­ing at the start of the im­muno-on­col­o­gy rev­o­lu­tion, and it’s been a re­al priv­i­lege cov­er­ing the ex­plo­sion of deals and col­lab­o­ra­tions that are be­ing struck now. Every day it seems brings one, or two, new I/O pacts. This week there was iOmx’s start­up round to fund the hunt for new check­point in­hibitors. Genen­tech struck a po­ten­tial­ly ground­break­ing part­ner­ship with BioN­Tech on us­ing mes­sen­ger RNA to de­vel­op per­son­al­ized can­cer vac­cines. With the three lead­ing check­points on the mar­ket and more com­ing, the po­ten­tial to part­ner on new com­bos is dri­ving bil­lions of dol­lars in fresh in­vest­ments. True, any­thing this hot will breed an ex­cess of al­ter­na­tives. In­vestors will get burned. The shake­out will have to oc­cur even­tu­al­ly and not every­one will suc­ceed. Many, most, will fail or fall by the way­side. But it’s been fun watch­ing the spot­light grow big­ger and more in­tense every week. I was chat­ting with an­oth­er CEO at a US start­up in this field ear­li­er in the week, and he be­lieves that we’re still just at the be­gin­ning of this i/o era. This will go on for an­oth­er 20 years, he says. And he’s like­ly right. What a great time to be in biotech.

 Set­backs hap­pen. It’s time for the big com­pa­nies to be more trans­par­ent about them.

Why do so many Big Phar­ma com­pa­nies have such a hard time talk­ing about a set­back? In re­cent times Am­gen nev­er missed a beat when it came to tout­ing their kid­ney dis­ease drug Parsabiv (etel­cal­ce­tide), and then the FDA un­ex­pect­ed­ly re­ject­ed it and the big biotech shut down, adopt­ing the tur­tle de­fense in re­fus­ing to even at­tempt to ex­plain it. No­var­tis likes to slip bad news in­to quar­ter­ly re­ports, in­clud­ing a line item on the re­cent re­jec­tion of one of its biosim­i­lars. And this week J&J could on­ly ac­knowl­edge, af­ter I con­tact­ed them, that the FDA had placed a hold on one of its can­cer drugs. They de­clined to ex­plain the se­ri­ous ad­verse events cit­ed on clin­i­cal­tri­ that forced reg­u­la­tors’ hands. I’ve said it be­fore and no doubt will have plen­ty of oc­ca­sions to do it again, but com­pa­nies run­ning drug stud­ies have a re­spon­si­bil­i­ty to ex­plain these sna­fus in some de­tail. They owe it to their in­vestors, the peo­ple who sign up for all of their clin­i­cal stud­ies and the sci­en­tists try­ing to make safe progress in the same field. There’s far too lit­tle trans­paren­cy in drug de­vel­op­ment. At a time when the in­dus­try is look­ing for some un­der­stand­ing from the pub­lic on the cost of in­no­va­tion, big play­ers should al­so rec­og­nize that they can be lead­ers in own­ing up to what can go wrong in de­vel­op­ing a new drug. It won’t hurt as much as they ev­i­dent­ly think it will.

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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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 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.

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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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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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.

Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Multiple antibiotic resistant Pseudomonas aeruginosa bacterium

A new way to in­fil­trate (and de­stroy) some of the dead­liest drug-re­sis­tant bugs

About four years ago, Ruben Tommasi, the gregarious scientific chief of antibiotics startup Entasis, walked into a meeting with his top chemist and top biologist to chew over another batch of unchanging results.

“It felt like we were running the same experiment over and over,” Tommasi told Endpoints News. “We had all sort of come to that point in time where we felt like we were banging our heads against the wall.”

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