#ES­MO17: Eli Lil­ly sets the stage for a CDK 4/6 show­down with Pfiz­er, No­var­tis — but not ex­act­ly to its ad­van­tage

MADRID — Eli Lil­ly came to ES­MO with an eye to dis­tin­guish­ing abe­maci­clib as it pre­pares to launch its CDK 4/6 can­cer drug against ri­vals from No­var­tis and Pfiz­er. It may have done that, but not ex­act­ly as Lil­ly ex­ecs would have liked.

Cur­rent­ly un­der pri­or­i­ty re­view at the FDA, abe­maci­clib reg­is­tered the pos­i­tive da­ta need­ed to win over reg­u­la­tors in MONARCH-3. Re­searchers tracked a 46% re­duc­tion in the risk of dis­ease pro­gres­sion in the tri­al arm in­clud­ing pre­vi­ous­ly un­treat­ed women with ad­vanced breast can­cer, com­par­ing a com­bi­na­tion of abe­maci­clib added to stan­dard care. There was al­so a 59% re­sponse rate on tu­mor shrink­age com­pared to 44% in the con­trol arm pro­vid­ed stan­dard ther­a­py.

The me­di­an pro­gres­sion-free sur­vival rate and over­all sur­vival num­bers aren’t in yet.

That’s all ap­proval-wor­thy da­ta, but not nec­es­sar­i­ly the kind of ear­ly ef­fi­ca­cy re­sults that will in­tim­i­date any­one at Pfiz­er and No­var­tis wor­ried about mar­ket share.

Where it gets trou­ble­some for Eli Lil­ly, though, is on the side ef­fect da­ta.

Rates of di­ar­rhea and neu­trope­nia were 81.3% and 41.3% with abe­maci­clib, and 29.8% and 1.9% with place­bo, re­spec­tive­ly.

David Ricks, Eli Lil­ly CEO

The in­ves­ti­ga­tors are quick to say that the di­ar­rhea is typ­i­cal­ly fair­ly low grade and read­i­ly man­aged, but it’s the kind of com­mon ef­fect that could well per­suade doc­tors to pre­fer ei­ther Kisqali or Ibrance for their HR-pos­i­tive, HER2-neg­a­tive pa­tients.

That’s not the kind of dis­tin­guish­ing fac­tor you want to raise, es­pe­cial­ly when you’re late to the game.

Ever­core ISI’s Umer Raf­fat al­so sent out a note on Sun­day high­light­ing an im­bal­ance of throm­boem­bol­ic events, which could earn a warn­ing la­bel from the FDA that would give com­peti­tors a dis­tinct edge as well.

Not good.

Eli Lil­ly has as­sert­ed that it can make abe­maci­clib the best-in-class pick among the three CDK 4/6 drugs field­ed by three phar­ma gi­ants with se­ri­ous sales ef­forts. And that con­fi­dence has built peak sales es­ti­mates to close to $2 bil­lion a year. For now.

Re­searchers al­so high­light­ed new ev­i­dence that sug­gests there are pa­tient groups that would ben­e­fit more by start­ing on stan­dard ther­a­py and adding a CDK 4/6 drug as a sec­ond-line ther­a­py.

“Now for the first time,we have in­sights sug­gest­ing that pa­tients with cer­tain clin­i­cal char­ac­ter­is­tics may ben­e­fit dif­fer­ent­ly from treat­ment with a CDK 4/6 in­hibitor, in­clud­ing the pos­si­bil­i­ty that some pa­tients with a good prog­no­sis may be able to start on en­docrine ther­a­py alone,” said lead au­thor An­ge­lo Di Leo. “In such pa­tients, CDK 4/6 in­hibitors could po­ten­tial­ly be re­served as a next line of treat­ment for metasta­t­ic dis­ease. This idea war­rants fur­ther study giv­en our da­ta. In our study, near­ly one-third of pa­tients had bone metas­tases on­ly or a tu­mor re­laps­ing sev­er­al years af­ter stop­ping ad­ju­vant en­docrine ther­a­py. This is a clin­i­cal­ly rel­e­vant pro­por­tion of pa­tients for whom we may con­sid­er de­lay­ing use of a CDK 4/6 in­hibitor. This may be a more op­ti­mal treat­ment strat­e­gy for some pa­tients since it can avoid the tox­i­c­i­ty of first line CDK 4/6 in­hibitors and save costs.”

Pay­ers won’t over­look that ob­ser­va­tion.

We won’t have long to wait be­fore things heat up on the mar­ket. Lil­ly nabbed a pri­or­i­ty re­view for this drug in Ju­ly, set­ting up a fi­nal de­ci­sion by Jan­u­ary.

Lil­ly needs a steady stream of sig­nif­i­cant new drug ap­provals if new CEO Dave Ricks ex­pects to keep its in­vestors hap­py. The FDA have helped out by putting baric­i­tinib back on track, but we won’t know that for sure un­til next year.

Im­age cred­it: ES­MO

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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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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Stephen Squinto, Gennao Bio CEO (Gennao)

Alex­ion co-founder Stephen Squin­to is back in the game as CEO, this time for a small gene ther­a­py play­er

With his name already behind a rare disease success story in Alexion, Stephen Squinto was looking for a great story to drive him to jump back into the biotech game. He found that in a fledging non-viral gene therapy company, and now he’s got a few backers on board as well.

On Tuesday, Gennao Bio launched with a $40 million Series A co-led by OrbiMed and Logos Capital with participation by Surveyor Capital. The biotech, which is looking to use its cell-penetrating antibody platform to deliver nucleic acid “payloads” during into the nucleus, had to rush for its initial series — and had a name change along the way.

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.