Wel­come Imfinzi: As­traZeneca crash­es the check­point par­ty late with a green light for dur­val­um­ab

And then there were 5.

The FDA hand­ed out its lat­est ap­proval for a PD-L1 check­point in­hibitor on Mon­day af­ter­noon, giv­ing a green light to As­traZeneca to start sell­ing dur­val­um­ab as Imfinzi as a sec­ond-line ther­a­py for metasta­t­ic urothe­lial car­ci­no­ma.

Pas­cal So­ri­ot

The reg­u­la­to­ry OK comes in the wake of ap­provals for Mer­ck, Bris­tol-My­ers Squibb, Roche/Genen­tech and Pfiz­er/Mer­ck KGaA. The bi­ol­o­gy of these new check­point drugs is well un­der­stood now, and the FDA is­sued its ap­proval af­ter a rel­a­tive­ly small, sin­gle-arm study.

Reg­u­la­tors waved this one through af­ter giv­ing dur­val­um­ab a break­through drug des­ig­na­tion and pri­or­i­ty re­view, even though its the third ap­proval for a check­point ther­a­py in blad­der can­cer.

Dur­val­um­ab’s longterm suc­cess is cru­cial to the fu­ture of As­traZeneca and CEO Pas­cal So­ri­ot. Billed as a block­buster-to-be, fol­low­ing a com­mer­cial trail al­ready clear­ly laid out, the big show­down for As­traZeneca comes lat­er in the year, when it rolls out late-stage da­ta on a com­bi­na­tion of its check­point com­bo in its MYS­TIC study, which match­es dur­val­um­ab with treme­li­mum­ab, a CT­LA-4 sim­i­lar to Yer­voy, for lung can­cer.

The ju­ry is still out, though, on how well a CT­LA-4 drug — with all its at­ten­dant tox­i­c­i­ty — will do in this field. That’s one rea­son why Bris­tol-My­ers Squibb re­cent­ly inked a deal with Cy­tomX on a next-gen CT­LA-4 that might prove far bet­ter for pa­tients.

Sea­mus Fer­nan­dez at Leerink not­ed some mod­est ex­pec­ta­tions on this first ap­proval. The up­side lies fur­ther down the road.

Al­though this in­di­ca­tion rep­re­sents a rel­a­tive­ly small op­por­tu­ni­ty for AZN (we fore­cast Imfinzi cap­tur­ing 10% of our es­ti­mat­ed ~$2.3B WW blad­der can­cer mar­ket), the ap­proval will al­low the agent to be­come more fa­mil­iar with on­col­o­gists and should help fa­cil­i­tate fu­ture sBLAs for drug. The ma­jor in­di­ca­tion for Imfinzi re­mains first-line (1L) non-small cell lung can­cer (NSCLC) and we await top-line da­ta from the Phase 3 MYS­TIC tri­al in com­bi­na­tion with treme­li­mum­ab (an­ti-CT­LA-4) ex­pect­ed in mid-2017.

As­traZeneca, mean­while, raised a red flag last week when it de­layed its third-line read­out in the ARC­TIC study of the duo, spurring some sus­pi­cions that it was on track to a trou­bling fail­ure that would have raised se­ri­ous doubts about its fu­ture in the field.

The oth­er ques­tion that many of us have is how many of these PD-1/PD-L1 check­points can be ap­proved be­fore they start slic­ing and dic­ing this mar­ket in­to ever small­er bites. A range of sec­ond-wave check­points are in de­vel­op­ment now, with every­one that’s fi­nanced well enough and in­ter­est­ed in it go­ing af­ter one of their own.

That group in­cludes In­cyte, which has been part­ner­ing with the main­stream check­points in nonex­clu­sive arrange­ments. And the main play­ers, like Mer­ck and Bris­tol-My­ers, are al­ready well along with their own com­bi­na­tion tri­als. Hun­dreds of them.

The ap­proval, though, marks a big win for As­traZeneca, which has made sig­nif­i­cant progress on the on­col­o­gy front in the last few years. They had to have this one to re­main a cred­i­ble ri­val. And they got it.

The FDA has been on a drug ap­proval spree over the last few days. This is the fifth OK for a new chem­i­cal en­ti­ty in the last three work­ing days, bring­ing the year-to-date to­tal to 19. Last year, which saw a big dip in ap­provals, the FDA ap­proved a to­tal of 22 new drugs.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,300+ biopharma pros reading Endpoints daily — and it's free.

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
complex market.
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.

Stephen Hahn, AP

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,300+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,300+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,300+ biopharma pros reading Endpoints daily — and it's free.

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.

Daphne Zohar (PureTech)

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 70,300+ biopharma pros reading Endpoints daily — and it's free.