Bris­tol-My­ers craters af­ter block­buster check­point drug Op­di­vo fails key lung can­cer study

Bris­tol-My­ers Squibb an­nounced this morn­ing that Op­di­vo has flopped in a late-stage study on non-small cell lung can­cer, pre­sent­ing a stun­ning set­back for the star ther­a­py. Its shares $BMY im­me­di­ate­ly plunged 18%, wip­ing out bil­lions in mar­ket val­ue, while ri­val Mer­ck $MRK—a run­ner-up in the check­point mar­ket—saw its shares soar 10%.

Re­searchers had re­cruit­ed a broad pop­u­la­tion of 541 pre­vi­ous­ly un­treat­ed first line pa­tients whose tu­mors ex­pressed PD-L1 at ≥ 5%, a key bio­mark­er used to iden­ti­fy pa­tients most like­ly to re­spond. The Op­di­vo arm was com­pared to a group who re­ceived their physi­cian’s choice of al­ter­na­tive ther­a­pies. But this time, in the first ma­jor re­ver­sal for Bris­tol-My­ers, the drug failed to de­liv­er a sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival.

The fo­cus now may cen­ter on the lev­el of PD-L1 ex­pres­sion used to qual­i­fy pa­tients. Last fall, when the FDA ex­pand­ed its ap­proval of Op­di­vo to NSCLC pa­tients whose can­cer had spread af­ter chemo, FDA can­cer czar Richard Paz­dur not­ed:

“While Op­di­vo showed an over­all sur­vival ben­e­fit in cer­tain non-small cell lung can­cer pa­tients, it ap­pears that high­er ex­pres­sion of PD-L1 in a pa­tient’s tu­mor pre­dicts those most like­ly to ben­e­fit.”

“The missed re­sult like­ly re­flects the fact that BMY pushed the en­ve­lope too far in de­sign­ing its tri­al,” not­ed Bern­stein’s Tim An­der­son. “Specif­i­cal­ly, as men­tioned in the press re­lease to­day, they chose a “cut-off val­ue” for PDL1 ex­pres­sion of 5%.  This is in-line with what we had been say­ing (that 5% was the val­ue), where­as the con­sen­sus view had been that the cut-off was 10%.  By mak­ing it 5%, BMY was in essence try­ing to broad­en the pa­tient pop­u­la­tion where it could claim a ben­e­fit (had re­sults been pos­i­tive, of course), but failed re­sults sug­gest they like­ly made it too broad, mean­ing they en­rolled pa­tients with too lit­tle PDL1 ex­pres­sion, and this soured the over­all analy­sis.  The pop­u­la­tion MRK stud­ied was nar­row­er.”

I/O in­vest­ment spe­cial­ist Brad Lon­car had this to say:

Bris­tol’s more ag­gres­sive strat­e­gy of fo­cus­ing on a broad­er pop­u­la­tion rather than high PD-L1 ex­pres­sors has worked out for them in lat­er stages of dis­ease, but it looks like that has fi­nal­ly reached its lim­it. This is a very dis­ap­point­ing re­sult, but I think they de­serve cred­it for try­ing to help as many pa­tients as pos­si­ble.

Mer­ck has been lag­ging far be­hind Bris­tol-My­ers Squibb in the check­point sales race, with

Gio­van­ni Caforio, Bris­tol-My­ers Squibb CEO

Op­di­vo OK’d for use with­out a di­ag­nos­tic test while Keytru­da pa­tients have to be screened. Free of test­ing pa­tients, Op­di­vo has raced far ahead on the sales front. But Keytru­da—which was test­ed in pa­tients with a PD-L1 ex­pres­sion of 50%—looks to have the edge now in a key mar­ket­place.

These two pi­o­neer­ing drugs work es­sen­tial­ly the same way. They both dis­man­tle a hur­dle that can­cer cells re­ly on to es­cape an at­tack by the im­mune sys­tem. That has proven to be a game-chang­er in many types of can­cer, where new com­bi­na­tions are now be­ing test­ed to pro­vide a one-two punch against can­cer cells.

Gio­van­ni Caforio, the CEO at Bris­tol, had this to say:

While we are dis­ap­point­ed Check­Mate -026 did not meet its pri­ma­ry end­point in this broad pa­tient pop­u­la­tion, we re­main com­mit­ted to im­prov­ing pa­tient out­comes through our com­pre­hen­sive de­vel­op­ment pro­gram, in­clud­ing the on­go­ing Phase 3 Check­Mate -227 study ex­plor­ing the po­ten­tial of the com­bi­na­tion of Op­di­vo plusYer­voy for PD-L1 pos­i­tive pa­tients, and Op­di­vo plus Yer­voy, or Op­di­vo plus chemother­a­py in PD-L1 neg­a­tive pa­tients.


via Brad Lon­car

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
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What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

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The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Mer­ck KGaA spin­out gets first fund­ing to bring dual-act­ing can­cer mol­e­cules in­to the clin­ic

Two and a half years after launch, Merck KGaA spinout iOnctura is getting its first major round of funding.

The oncology startup raised €15 million ($16.6 million) to put its lead drug into the clinic and get its second drug past IND-enabling tests. INKEF Capital and VI Partners co-led the round and were joined by the biotech’s longtime backer M Ventures, an arm of Merck KGaA, and Schroder Adveq.

Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

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PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

Cashing in on the exuberance around Karuna Therapeutics and its potential blockbuster CNS drug, PureTech has sold a chunk of the biotech’s shares to Goldman Sachs for $200 million.

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