New study of FDA cites the flaws be­hind rapid-fire can­cer drug OKs

Richard Padzur

Over the past few years the FDA’s on­col­o­gy group un­der Richard Paz­dur has tru­ly rev­o­lu­tion­ized the way can­cer drugs are de­vel­oped and re­viewed for mar­ket­ing ap­proval. In or­der to ramp up the ar­rival of new drugs, reg­u­la­tors waived old rules on over­all sur­vival, flag­ging their will­ing­ness to carve years out of the R&D process in or­der to field new ther­a­pies.

It was a straight up trade off. The FDA was will­ing to ac­cept pre­lim­i­nary ev­i­dence of ef­fi­ca­cy and safe­ty and de­lay con­fir­ma­to­ry stud­ies un­til af­ter a drug was on the mar­ket. And pa­tient groups have cheered the FDA on at every turn.

But there is an­oth­er per­spec­tive on how this is all play­ing out, now that we’re a few years in­to the brand new game of can­cer R&D.

A group of re­searchers, in­clud­ing some fa­mil­iar FDA crit­ics, took a look at 22 drugs that were giv­en an ac­cel­er­at­ed ap­proval. Three years af­ter ap­proval, on­ly half of the 38 con­fir­ma­to­ry stud­ies re­quired by the FDA had been com­plet­ed, and most still used end­points that had strayed far from the old gold stan­dard on ran­dom­ized sur­vival re­sults.

Huseyin Naci

The study, pub­lished by the Jour­nal of the Amer­i­can Med­ical As­so­ci­a­tion, was done by Huseyin Naci, Kate­lyn Smal­l­ey and Aaron Kessel­heim, a pol­i­cy ex­pert at Har­vard who’s been re­peat­ed­ly crit­i­cal of the FDA’s ap­proval process.

“Drugs grant­ed Ac­cel­er­at­ed Ap­proval should be rig­or­ous­ly eval­u­at­ed us­ing con­vinc­ing pa­tient-cen­tered clin­i­cal out­comes in rig­or­ous stud­ies,” Naci told Reuters. But, he added, “we have found nu­mer­ous sit­u­a­tions in which re­quired con­fir­ma­to­ry stud­ies with rig­or­ous de­signs and out­comes are not pur­sued or are not com­plet­ed in a time­ly fash­ion, and in these cas­es, we are con­cerned that reg­u­la­tors ap­pear to ac­cept da­ta that would not oth­er­wise meet FDA stan­dards.”

Don’t look for any sud­den tough­en­ing of can­cer R&D stan­dards at the FDA. As Scott Got­tlieb was un­der re­view for the top job at the agency, he her­ald­ed the can­cer group’s work in find­ing new ways to ap­prove on­col­o­gy drugs faster than ever be­fore, a game-chang­er in the field made pos­si­ble for drugs that are typ­i­cal­ly ini­tial­ly used as a last re­sort among drug-re­sis­tant, dy­ing pa­tients.

The em­pha­sis at the FDA is to make the rest of the agency more like the on­col­o­gy or­ga­ni­za­tion.

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.

Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

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UP­DAT­ED: 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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Ku­ra co-founder heads to Asian mul­ti-na­tion­al as biotech eyes the goal posts for lead drug

Six years after Kura Oncology snagged a farnesyl transferase inhibitor from J&J and leapt straight into clinical development, one of the biotech’s founders is leaving to start a new chapter in his career.

CMO and development chief Antonio Gualberto is exiting the company, and Kura — led by longtime biotech entrepreneur Troy Wilson — is on the hunt for a replacement. Wilson credited the CMO for some key biomarker work, including the discovery of the CXCL12 pathway as a target of their lead drug tipifarnib. Those biomarkers are being relied on to define the patient population most likely to benefit from the drug.

FDA waves Epizyme's $186K rare can­cer drug through to mar­ket — now get ready for the sec­ond act

After winning the hearts of the expert panel convened by the FDA despite a bleak in-house review and a checkered development history, Robert Bazemore has steered Epizyme to its first-ever OK for a rare cancer drug.

The approval in epithelioid sarcoma sets tazemetostat, now Tazverik, up nicely for a quick expansion to follicular lymphoma — a much bigger indication for which the biotech has just submitted an NDA.

2019 a 'trans­for­ma­tive year' for phar­ma M&A. Is that a good thing?

Big Pharma keeps getting bigger.

Fueled by the mega-mergers between Bristol-Myers Squibb and Celgene and between Allergan and AbbVie, the industry last year saw $350 billion worth of M&A, according to the new year-end report from the consultants at PwC.  That’s a more than 50% increase on 2018.

“I kind of look at 2019 as a transformational year,” report author Glen Hunzinger told Endpoints News. 

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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.

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