Takeda CEO Christophe Weber (Getty Images)

Take­da an­nounces pos­i­tive new ALK+ lung can­cer da­ta as list of crizo­tinib suc­ces­sors widens

Take­da un­veiled new Phase III front­line da­ta for their ALK in­hibitor at Eu­ro­pean So­ci­ety for Med­ical On­col­o­gy Asia Con­gress, show­ing it could de­ter the spread of lung can­cer for two years or more. But the tri­al com­pared the drug, Alun­brig (briga­tinib), against an ear­ly in­hibitor that is no longer best-in-class and the Japan­ese phar­ma will like­ly face sig­nif­i­cant com­pe­ti­tion if reg­u­la­tors grant an ex­pand­ed la­bel. 

“It’s part of the next gen­er­a­tion of ALK in­hibitors,” San­jay Popat, a tho­racic on­col­o­gist at Roy­al Mars­den Hos­pi­tal and an in­ves­ti­ga­tor on the tri­al, Al­ta-1L, told End­points News. “The up­dat­ed da­ta re­al­ly con­firms that briga­tinib is way su­pe­ri­or to crizo­tinib.”

San­jay Popat

The tri­al com­pared briga­tinib against crizo­tinib in 275 ad­vanced non-small-cell-lung-can­cer pa­tients who test­ed pos­i­tive for the ALK gene, and it pro­duced re­sults that don’t take a bio­sta­tis­ti­cian to un­der­stand.

The re­view com­mit­tee found pa­tients on briga­tinib went a me­di­an 24 months with­out the can­cer spread­ing, hit­ting the pri­ma­ry end­point. For crizo­tinib pa­tients? 11 months. (Take­da in­ves­ti­ga­tors found a slight­ly high­er PFS for briga­tinib and a slight­ly low­er PFS for crizo­tinib). 

In pa­tients whose can­cer had spread to the brain — a no­to­ri­ous­ly-dif­fi­cult place to de­liv­er com­pounds, in­clud­ing crizo­tinib — be­fore the start of the tri­al, the drug im­proved pro­gres­sion-free sur­vival by 76% against the con­trol arm, as as­sessed by in­ves­ti­ga­tors. 

“It’s de­signed to cross the blood-brain bar­ri­er,” Popat said of the drug. Pa­tients with brain metas­tases rep­re­sent­ed about 30% of each arm.

The prob­lem for Take­da is that the ALK-land­scape has changed con­sid­er­ably since the Phase III tri­al be­gan and since they ac­quired the com­pound in the $5.2 bil­lion Ari­ad deal. Even since the FDA grant­ed ac­cel­er­at­ed ap­proval for the drug as a sec­ond-line treat­ment in 2017.

Crizo­tinib, the con­trol in the tri­al, was the first ALK in­hibitor ap­proved and came with much ac­claim. While the drug was in Phase I in the late 2000s, the sto­ries of once-ter­mi­nal pa­tients watch­ing their tu­mors shrink made for TV news fod­der. But Pfiz­er, No­var­tis and Roche have all since un­veiled new in­hibitors that can be more ef­fec­tive than the first drug.

Re­searchers cau­tion against com­par­ing clin­i­cal tri­als too di­rect­ly, but Roche’s Ale­cen­sa al­so showed dra­mat­i­cal­ly im­proved pro­gres­sion free-sur­vival against crizo­tinib in sim­i­lar pa­tient pop­u­la­tions, bol­stered by im­proved re­sults in the cen­tral ner­vous sys­tem metas­tases.

Still, the drugs are not iden­ti­cal and, as with many can­cer drugs, re­sis­tance has be­come a prob­lem, with pa­tients rid­ing one in­hibitor while it works and then go­ing to the next. That makes each new in­hibitor a po­ten­tial life­line.

“The one thing that’s clear is that each of the next-gen in­hibitors have demon­strat­ed true su­pe­ri­or­i­ty,” Popat said. “So choos­ing which one is a de­ci­sion be­tween pa­tients and their on­col­o­gists.”

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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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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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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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.

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 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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