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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

FDA spells out how can­cer drug de­vel­op­ers can use one tri­al for both ac­cel­er­at­ed and full ap­provals

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

Lat­est on ul­tra-rare dis­ease ap­proval; Pos­i­tive, if mixed, signs for Bio­gen's ALS drug; Clay Sie­gall finds a new job; and more

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Over the last four years, we’ve honored 80 women whose extraordinary accomplishments have changed the game in biopharma R&D. You can now nominate someone to be highlighted in this year’s special report. Details are here.

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No­vo Nordisk oral semaglu­tide tri­al shows re­duc­tion in blood sug­ar, plus weight loss

Novo Nordisk is testing higher levels of its oral version of its GLP-1, semaglutide, and its type 2 diabetes trial results released today show reductions in blood sugar as well as weight loss.

In the Phase IIIb trial, Novo compared its oral semaglutide in 25 mg and 50 mg doses with the 14 mg version that’s currently the maximum approved dose. The trial looked at how the doses compared when added to a stable dose of one to three oral antidiabetic medicines in people with type 2 diabetes who were in need of an intensified treatment.

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Ly­me vac­cine test com­ple­tion is pushed back by a year as Pfiz­er, Val­ne­va say they'll ad­just tri­al

Valneva and Pfizer have adjusted the end date for the Phase III study of their investigational Lyme disease vaccine, pushing it back by a year after issues at a contract researcher led to thousands of US patients being dropped from the test.

In a March 20 update to clinicaltrials.gov, Valneva and Pfizer moved the primary completion date on the trial, called VALOR, from the end of 2024 to the end of 2025.

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Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

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FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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Sijmen de Vries, Pharming CEO

FDA ap­proves Pharm­ing drug for ul­tra-rare im­mun­od­e­fi­cien­cy dis­ease

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.

Stuart Peltz, former PTC Therapeutics CEO

Stu­art Peltz re­signs as PTC Ther­a­peu­tics CEO af­ter 25 years

Stuart Peltz, the longtime CEO of PTC Therapeutics who’s led the rare disease drug developer since its founding 25 years ago, is stepping down.

Succeeding him in the top job is Matthew Klein, who joined PTC in 2019 and was promoted to chief operating officer in 2022. In a call with analysts, he said the CEO transition has been planned for “quite some time” — in fact, as part of it, he gave the company’s presentation at the JP Morgan healthcare conference earlier this year.

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