#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

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Michel Vounatsos, Getty Images

UP­DAT­ED: Stay tuned: Bio­gen’s num­bers are great — it’s their wor­ri­some fu­ture that leaves an­a­lysts skit­tish

Biogen came out with an upbeat assessment of their Q2 numbers today, discounting the arrival of a key rival for its blockbuster Spinraza franchise. But the top execs remain grimly determined to not say much anything new about the sore points that have dragged down its stock, including the future of its big investment in Alzheimer’s or how it plans to invest the considerable cash that the big biotech continues to reap.

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Why wait? Cel­gene re­struc­tures a big Jounce pact — ze­ro­ing in on new I/O path­way with $530M deal and bump­ing ICOS

Celgene’s business team isn’t waiting for the big merger with Bristol-Myers Squibb to go through before syncing its strategy with the new mother ship.

Tuesday evening the big biotech unveiled a $530 million deal — $50 million in upfront cash — to amend their alliance with Jounce Therapeutics $JNCE to gain worldwide rights to JTX-8064, an antibody that targets the LILRB2 receptor on macrophages. Their old, $2.6 billion deal is being scrapped, leaving Jounce with a pipeline that includes the lead drug, the ICOS-targeting vopratelimab.

PACT Phar­ma says it's per­fect­ed the tech to se­lect neoanti­gens for per­son­al­ized ther­a­py — now on­to the clin­ic

At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.

UP­DAT­ED: My­ovan­t's uter­ine fi­broid drug looks com­pet­i­tive in PhI­II — but can they van­quish mighty Ab­b­Vie?

Vivek Ramaswamy’s Myovant $MYOV has closely matched its positive first round of Phase III data for their uterine fibroid drug relugolix, setting up a head-to-head rivalry with pharma giant AbbVie as the little biotech steers to the market with a planned filing in Q4.

Here’s how Myovant plans to prevail over the AbbVie $ABBV empire.

In the study, 71.2% of women receiving once-daily relugolix combination therapy achieved the clinical response they were looking for, compared to only 14.7% in the control arm. The data comfortably reflected the same outcomes in the first Phase III — 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo — which will reassure regulators that they are getting the carefully randomized data that qualifies for the FDA’s gold standard for success.

Lit­tle Mar­i­nus sees its shares eclipsed as the Sage ri­val fails to com­pare on PPD in PhII

The executive team at Sage $SAGE have skirted another potential pitfall on its way to racking up a big future for its depression drug Zulresso.

Little Marinus Pharmaceuticals $MRNS had sought to challenge the Sage drug with an IV formulation — followed by an oral version — of ganaxolone for postpartum depression. But researchers say their Phase II study failed to positively differentiate itself from a placebo at 28 days — leaving them to hold up “clinically meaningful” data within the first day of administration compared to the control arm.

Roche cuts loose Tam­i­flu OTC rights, hand­ing Sanofi the keys as the phar­ma gi­ant dou­bles down on Xofluza

Roche set out to make a better flu medicine than Tamiflu as that franchise was headed to a generic showdown. Now they’ll see just how well Xofluza stacks up against the mainstay drug after handing off over-the-counter rights in the US to Sanofi.

Sanofi $SNY says it will now step in to negotiate a deal with the FDA to steer Tamiflu into the OTC market, a role that could well involve new studies to ease passage of the drug out of doctor’s hands and into the consumer end of the market. And the French pharma giant will have first dibs over “selected” OTC markets around the world as they push ahead.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.