Puma shares ripped af­ter grow­ing grade 3 di­ar­rhea threat is high­light­ed in an ab­stract

Simos Sime­oni­dis, RBC Cap­i­tal

The skep­tics ripped in­to Puma Biotech­nol­o­gy $PBYI to­day, tear­ing a 20% chunk out of its share price by ear­ly af­ter­noon on Mon­day af­ter get­ting a glimpse of its lead can­cer drug’s con­tin­u­ing prob­lems spurring se­vere cas­es of di­ar­rhea in pa­tients.

The re­ac­tion quick­ly set in af­ter Puma post­ed an ab­stract for an up­com­ing can­cer sym­po­sium which spelled out the in­creas­ing rates in ner­a­tinib tri­als. RBC’s Simos Sime­oni­dis sat down to com­pare the num­bers, and reached a few un­set­tling con­clu­sions. Here’s a note he post­ed Mon­day af­ter­noon:

In an ab­stract re­leased this morn­ing, Puma dis­closed da­ta from the Phase II CON­TROL tri­al in the ex­tend­ed ad­ju­vant set­ting show­ing that treat­ment with lop­eramide helps low­er the ~40% Grade 3 (G3) di­ar­rhea seen in the Ex­teNET Phase III tri­al. How­ev­er, the num­bers re­leased to­day show that the G3 rates went up com­pared to what was dis­closed last year… Specif­i­cal­ly, in pa­tients in the orig­i­nal lop­eramide pro­to­col, the rate of G3 di­ar­rhea in­creased to 21.4% from 18.5%. Fur­ther­more, in the amend­ed pro­to­col arm, the amount of G3 di­ar­rhea more than dou­bled from 13% to 28.6%. Over­all, the blend­ed rate be­tween these two arms was 27.1% vs. 16% last year.

The com­pa­ny had re­cent­ly dis­closed they had added a new arm to the study, com­bin­ing the cor­ti­cos­teroid budes­onide to help with the pro­phy­lax­is reg­i­men. To­day’s re­lease of the wors­en­ing (vs. last year’s da­ta) di­ar­rhea, helps ex­plain the need for this change in the tri­al. While we view the 12.5% rate of G3 di­ar­rhea as po­ten­tial­ly promis­ing, we point to the small n (16 pa­tients) and to the fact that these da­ta are still ear­ly (i.e. it is pos­si­ble that they ac­tu­al­ly get worse over time, just as the da­ta from arms 1 and 2 did). The up­date in San An­to­nio should have slight­ly more ma­ture da­ta; how­ev­er, we view the fact that lop­eramide alone no longer ap­pears suf­fi­cient to pro­phy­laxe against se­vere di­ar­rhea as a sig­nif­i­cant neg­a­tive for ner­a­tinib and the stock.

One key point here: Sime­oni­dis has been cau­tious but pos­i­tive about ner­a­tinib’s prospects as a new treat­ment for breast can­cer as it un­der­goes scruti­ny at the FDA. Datasets on 5-year sur­vival and lop­eramide pro­phy­lax­is had im­proved sen­ti­ment around the com­pa­ny’s chances, he not­ed last Sep­tem­ber 20, when the FDA ac­cept­ed Puma’s ap­pli­ca­tion for re­view.

The bear po­si­tion on Puma is that the drug could be too tox­ic even for the FDA, which has proven will­ing to put up with sig­nif­i­cant threats for drugs ini­tial­ly aimed at dy­ing pa­tients. Bulls be­lieve that the safe­ty bar is low enough to clear.

In­vestors were way ahead of Sime­oni­dis to­day, dri­ving down the com­pa­ny stock as Twit­ter quick­ly spread the word to any­one who hadn’t heard al­ready.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Eli Lil­ly's an­ti­body cuts risk of Covid-19 by up to 80% among the most vul­ner­a­ble — but will it have a place next to vac­cines?

Eli Lilly says bamlanivimab lowered the risk of contracting symptomatic Covid-19 in a first-of-its-kind trial involving nursing home residents and staff, paving the way for a new option to protect against the virus.

But how big of an impact it might have, and what role it will play, at a time vaccines are being rolled out to the exact population it is targeting still remains unclear.

Among 965 participants in the study — all of whom tested negative for the coronavirus at baseline — the number of symptomatic cases reported in the bamlanivimab arm was 57% lower than that in the placebo arm (odds ratio 0.43, p=0.00021). In addition to that primary endpoint, all secondary endpoints reached statistical significance.

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Janet Woodcock (AP Images)

End­points poll: Janet Wood­cock takes the (in­ter­im) helm at the FDA. And a large ma­jor­i­ty of our read­ers want her to stay there

It’s official: Janet Woodcock is now the acting chief of the FDA.

And — according to an Endpoints poll — most industry readers would like her to stay there, although a significant minority is strongly opposed.

To recap: Joe Biden is reportedly choosing between Woodcock and former deputy FDA commissioner Joshua Sharfstein as his nominee for the permanent position. Given their respective track records, the decision is set to determine the agency’s lodestar for years to come.

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What’s next for End­points — and how to sup­port our in­de­pen­dent bio­phar­ma news mis­sion

The firehose of biopharma news is gushing these days.

That’s why broader and deeper is the theme for 2021 at Endpoints. You can expect new coverage outside our core R&D focus, with deeper reporting in some key areas. When John Carroll and I launched Endpoints nearly five years ago, we were wading in waist-high waters. Now we’re a team of 25 full-time staffers (and growing) with plans to cover the flood of biopharma news, Endpoints-style.

Charlie Fuchs, Roche and Genentech global head of product development for oncology and hematology (Yale Cancer Center)

Yale can­cer spe­cial­ist Char­lie Fuchs tapped as new glob­al de­vel­op­ment chief for Roche/Genen­tech

Roche and their big sub Genentech have just recruited a top cancer specialist at Yale to head up global product development in oncology and hematology.

I just got word that the pharma giant, which leads one of the most active cancer research operations in the world, recruited Charlie Fuchs, director of the Yale Cancer Center and physician-in-chief of Smilow Cancer Hospital. He’ll join the global operation March 1 and will be based in South San Francisco, where Genentech is based.

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Jonathan Weissman (MIT)

Can a new CRISPR tech­nique un­lock the se­crets of how can­cer spreads?

Jonathan Weissman’s team watched the cancer cells spread across the doomed mouse. Engineered with a bioluminescent enzyme, they appeared in scans first as a small navy blue diamond lodged near the heart; a week later, as a triangle splayed across the mouse’s upper body, with streaks of green and two distinct bright red hubs of activity. By day 54, the mouse resembled a lava lamp.

The images would have been familiar to any cancer biologist, but they didn’t actually tell you much about what was going on: why the cancer was metastasizing or which cells were responsible. For that, Weissman’s team had designed a new tool. Inside the original navy blue diamond, they had engineered the microbiological equivalent of an airplane’s black box — a “molecular recorder” that, after the mouse’s death, could allow them to extract the cells and wind back intimate footage of a single cancer’s ascent.

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Glax­o­SmithK­line scraps a LAG3 study, mark­ing an­oth­er fail­ure for the pipeline af­ter a crit­i­cal set­back

Another gap has appeared in GlaxoSmithKline’s pipeline.

Friday morning the Australian biotech Immutep put out word that Hal Barron’s R&D group at GSK had decided to scrap a Phase II proof-of-concept study in ulcerative colitis for their anti-LAG3 therapy GSK2831781. According to the biotech, the program didn’t survive an interim review.

The trial was stopped by GSK based on the assessment of clinical data as part of a planned interim analysis conducted in consultation with the trial’s Data Review Committee. GSK is conducting further reporting, assessment and analyses of the efficacy and safety data and evaluating the biology to determine next steps for the GSK2831781 development program.

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Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.