Trad­ing places with Bris­tol-My­ers, Mer­ck hit with an­oth­er late-stage set­back on check­point star Keytru­da

Close to a year af­ter Mer­ck $MRK won an ac­cel­er­at­ed FDA OK to use its PD-1 check­point star Keytru­da for treat­ing sec­ond-line cas­es head and neck squa­mous cell car­ci­no­ma in com­bi­na­tion with plat­inum-con­tain­ing chemo, the phar­ma gi­ant an­nounced that its big Phase III study for that in­di­ca­tion failed.

The piv­otal KEYNOTE-040 tri­al failed to meet the pri­ma­ry end­point on over­all sur­vival in com­par­ing the block­buster check­point against stan­dard ther­a­pies, the phar­ma gi­ant re­port­ed. But the cur­rent ap­proval stands nev­er­the­less, Mer­ck said in a state­ment.

“The com­pa­ny not­ed that the FDA re­mains com­fort­able with the drug’s cur­rent ac­cel­er­at­ed ap­proval in this in­di­ca­tion de­spite the tri­al re­sults,” ob­served Leerink’s Sea­mus Fer­nan­dez. “Im­por­tant­ly, Keytru­da ap­pears to have an­oth­er shot on goal for full ap­proval in H&N can­cer, as the Keynote-048 study in first-line pa­tients could, if pos­i­tive, serve as the con­fir­ma­to­ry tri­al.”

Roger Perl­mut­ter, Mer­ck

Mer­ck didn’t pro­vide a lot of de­tails, but this is the lat­est in a se­ries of set­backs in the field that have be­gun to show the out­er lim­its of ef­fi­ca­cy for a new class of can­cer med that has trans­formed on­col­o­gy ther­a­py in the past two years. But right now, those out­er lim­its of ef­fi­ca­cy run along a blur­ry line, with no clear ex­pla­na­tions for what is caus­ing these sud­den break­downs.

Mer­ck re­cent­ly was forced to put a slate of 3 Keytru­da tri­als for mul­ti­ple myelo­ma on hold af­ter in­ves­ti­ga­tors spot­ted a high­er rate of death in the check­point arm. Two of those stud­ies used com­bi­na­tions with Cel­gene drugs, Po­m­a­lyst and its big drug Revlim­id.

Mer­ck has ini­ti­at­ed hun­dreds of stud­ies, in­clud­ing some 300 com­bi­na­tion stud­ies, as it races to cap­i­tal­ize on its new lead in the field af­ter Bris­tol-My­ers Squibb ran in­to se­ri­ous is­sues with a failed study for lung can­cer. It’s clear that af­ter see­ing some re­mark­able im­prove­ments for a sig­nif­i­cant mi­nor­i­ty of check­point pa­tients, these ther­a­pies have their lim­its. Roche has al­so had its own prob­lems with the fail­ure of a Phase III con­fir­ma­to­ry study us­ing Tecen­triq.

Bris­tol-My­ers’ Op­di­vo, mean­while, post­ed pos­i­tive Phase III da­ta on squa­mous cell car­ci­no­ma of the head and neck back in late 2016, with a me­di­an OS of 7.5 months for Op­di­vo com­pared to 5.1 months for in­ves­ti­ga­tor’s choice.

What to make of that?

“Up un­til yes­ter­day,” not­ed Ever­core ISI’s Umer Raf­fat, “I would have told you that there are at least 2 dif­fer­ent in­di­ca­tions where MRK worked and oth­ers failed … and per­haps MRK is just ex­e­cut­ing these tri­als much bet­ter.  How­ev­er, as of to­day, there ap­pears to be no con­sis­ten­cy in the in­con­sis­ten­cy.  Now MRK failed where BMY worked.”

“We are en­cour­aged by the pos­i­tive im­pact that KEYTRU­DA has had on many can­cer pa­tients, in­clud­ing those with pre­vi­ous­ly treat­ed re­cur­rent or metasta­t­ic head and neck can­cer, and we re­main con­fi­dent that KEYTRU­DA is an im­por­tant ther­a­py for this dif­fi­cult-to-treat can­cer,” said Roger Dansey, late-stage on­col­o­gy de­vel­op­ment leader, Mer­ck Re­search Lab­o­ra­to­ries. “We look for­ward to shar­ing the com­pre­hen­sive da­ta analy­sis from KEYNOTE-040 with the sci­en­tif­ic com­mu­ni­ty at an up­com­ing med­ical meet­ing.”

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

UP­DAT­ED: Gink­go Bioworks re­sizes the de­f­i­n­i­tion of go­ing big in biotech, rais­ing $2.5B in a record SPAC deal that weighs in with a whop­ping $15B-plus val­u­a­tion

Ginkgo Bioworks execs always thought big. But today should redefine just how big an upstart biotech player can dream.

In the largest SPAC deal to clear the hurdles to Nasdaq, the biotech that envisioned everything from remaking synthetic meat to a whole new approach to developing drugs has joined forces with one of the biggest disruptors in biotech to slam the Richter scale on dealmaking.

Soon after becoming the darling of the VC crew and clearing the bar on a $4 billion valuation, Ginkgo — a synthetic biotech player out to reprogram cells with industrial efficiency — has now struck a deal to go public in the latest leviathan SPAC that sets its pre-money valuation at $15 billion. In one swift vault, Ginkgo will combine with Harry Sloan’s Soaring Eagle Acquisition Corp. and leap into the public markets.

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FDA un­veils six ICH guide­lines ahead of meet­ing with Health Cana­da

A sign that the FDA’s non-Covid-related processes are beginning to normalize: The release of six guidelines from the International Council of Harmonisation.

Years in development, the ICH documents offer an international perspective on drug development, with these latest guidelines covering everything from recommendations to support the classification of drug substances, featured in the M9 guidance, to standards for nonclinical safety studies for pediatric medicines in the S11 guideline.

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Sanofi, Glax­o­SmithK­line, Boehringer ac­cused of play­ing games, de­stroy­ing emails re­lat­ed to law­suit over con­t­a­m­i­nat­ed Zan­tac

A recent court filing raises new questions about how major pharma companies like Sanofi, GlaxoSmithKline, and Boehringer Ingelheim have dealt with a lawsuit related to recalls of certain over-the-counter heartburn drugs due to the presence of a potentially cancer-causing substance found in them.

More than 70,000 people who took Sanofi’s Zantac and other heartburn drugs containing ranitidine, which have been recalled over the past two years, have sued the manufacturers, including generic drugmakers, and other retailers and distributors as part of a consolidated suit before US District Court Judge Robin Rosenberg in Florida.

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Alvotech takes Ab­b­Vie to court over al­leged patent 'mine­field' sur­round­ing megablock­buster Hu­mi­ra

AbbVie has so far been successful in shooing away competition to its megablockbuster Humira, deploying a number of patents and settlements to keep biosimilars off the US market until 2023. But one Icelandic drugmaker doesn’t want to wait — and on Tuesday, it filed a lawsuit challenging what it called a patent “minefield.”

Alvotech has accused AbbVie of trying to “overwhelm” and “intimidate” it with “an outrageous number of patents of dubious validity,” according to court documents. The company is currently seeking approval for its Humira copycat AVT02, which AbbVie says would infringe upon 62 patents.

UP­DAT­ED: Feds charge an­oth­er CRO staffer with fak­ing da­ta in a Glax­o­SmithK­line pe­di­atric asth­ma study

A Florida woman has been indicted as part of a clinical trial fraud scheme over a GlaxoSmithKline pediatric asthma study, the Justice Department announced Tuesday, the latest development in a case where three individuals have already pleaded guilty.

Jessica Palacio was charged with participating in a plot to falsify medical records, giving off the appearance that trial participants were making their scheduled visits to a Miami CRO and taking an experimental asthma medication as required. Palacio was also charged with lying to FDA investigators about her conduct.

Al Sandrock, Biogen R&D chief (Biogen via YouTube)

UP­DAT­ED: Bio­gen push­es in a fresh stack of chips and starts prep­ping a glob­al R&D game plan af­ter watch­ing the cards turn on ear­ly throm­bolyt­ic da­ta

After patiently steering through a decade-long journey for its early-stage clinical work, a small Tokyo biotech has clinched a deal to out-license its lead thrombolytic agent to US heavyweight Biogen — which sees a potentially game-changing impact on the clot-busting field after taking a careful look at some upbeat Phase IIa data.

Three years after Biogen anted up $4 million to gain an option on the drug from TMS, the big US biotech is making a small bet to beef up its stroke portfolio. The BD team inked a deal to go ahead and grab rights to the drug for $18 million, with another $335 million in milestone cash on the table for a successful outcome.

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Chris Garabedian (Xontogeny)

Per­cep­tive Ad­vi­sors, Xon­toge­ny bring the band back and then some with a $515M sec­ond fund sniff­ing out lead com­pounds

When Perceptive Advisors and startup accelerator Xontogeny initially teamed up on an early-stage VC round in 2019, the partners hoped to prove their investments could be a force multiplier for early-stage companies. Now, with that proof of concept behind them, the pair have closed a second VC round worth more than double the money.

Dubbed PXV Fund II and headed by Xontogeny CEO and former Sarepta head Chris Garabedian, the $515 million fund will target 10 to 12 early-stage preclinical companies with Series A rounds in the $20 million to $40 million range with opportunities for Series B follow-ups. The oversubscribed fund is bringing the band back with initial investors from PXVI as well as new investors that include “top-tier” asset managers, endowments, foundations, family offices, and individual investors.

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A clos­er look at the FDA’s more than 700 pan­dem­ic-re­lat­ed record re­quests to re­place on­site in­spec­tions

As the pandemic constrained the FDA’s ability to travel for onsite manufacturing inspections, the agency increasingly turned to requesting records to fill the gap, even for hundreds of US-based facilities.

FDA explains in its guidance on manufacturing inspections during the pandemic that the agency can request records (not to be confused with the FDA’s remote interactive evaluations) directly from facilities “in advance of or in lieu of” certain onsite inspections. Companies are legally required to fulfill those requests because a denial may be considered limiting an inspection, which could lead to the FDA deeming a drug made at that site to be adulterated.

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