No­var­tis wins a key OK for Kym­ri­ah, but con­tin­u­ing man­u­fac­tur­ing woes hob­ble roll­out — ri­val Gilead CAR-T breaks in­to Eu­rope

No­var­tis CAR-T man­u­fac­tur­ing woes are con­tin­u­ing to put a crimp in its abil­i­ty to pro­vide ther­a­py to all po­ten­tial pa­tients.

Vas Narasimhan

The phar­ma gi­ant re­port­ed this morn­ing that the EC has stamped its ap­proval on mar­ket­ing Kym­ri­ah in Eu­rope for B-cell acute lym­phoblas­tic leukemia as well as treat­ment-re­sis­tant adults suf­fer­ing from dif­fuse large B-cell lym­phoma. But No­var­tis can on­ly make it avail­able to chil­dren with ALL now — adults will have to wait.

No­var­tis’s top ex­ecs have worked hard to smooth things over with an­a­lysts, but it’s been be­dev­iled by man­u­fac­tur­ing is­sues through­out the de­vel­op­ment stage and con­tin­ues to be af­fect­ed as it goes toe-to-toe with Gilead’s Kite, ap­proved for large B-cell lym­phoma. And Gilead is still com­ing on strong, not­ing this morn­ing that they re­ceived a Eu­ro­pean OK to mar­ket Yescar­ta for dif­fuse and pri­ma­ry me­di­asti­nal large B-cell lym­phoma.

A month ago No­var­tis CEO Vas Narasimhan not­ed dur­ing the Q2 call that:

I think it’s ear­ly days and we’ve al­ways said this is go­ing to be a five-year jour­ney with Kym­ri­ah to re­al­ly get us to be the glob­al­ly suc­cess­ful brand we want it to be.

On man­u­fac­tur­ing, we have seen some vari­abil­i­ty in our prod­uct spec­i­fi­ca­tions. This is some­thing we’re look­ing at now in DL­B­CL to make sure that we can con­tin­ue to ramp-up the de­mand. We feel con­fi­dent in the over­all longer-term out­look for Kym­ri­ah.

Liz Bar­rett

Liz Bar­rett, who runs No­var­tis on­col­o­gy, had this to say:

I think the most im­por­tant thing to let you know is that the vari­abil­i­ty that we’ve seen in the com­mer­cial spec­i­fi­ca­tions, which isn’t un­usu­al with a new ther­a­py as you launch in­to a new tar­get pa­tient pop­u­la­tion, is that we have still been able to de­liv­er fi­nal prod­uct to the ma­jor­i­ty of pa­tients.

As we’ve re­port­ed, though, the cell man­u­fac­tur­ing chief’s of­fice has been out­fit­ted with a re­volv­ing door at No­var­tis in re­cent years. Karen Walk­er left that post in ear­ly 2017, fol­lowed last spring by Spencer Fisk as he jumped ship to join the No­var­tis ex­ecs at Ru­bius. Those de­par­tures came on top of a ma­jor re­vamp for the cell and gene ther­a­py unit in 2016, which raised ques­tions at the time about No­var­tis’ abil­i­ty to keep up with Kite — though the phar­ma gi­ant wound up with the pi­o­neer­ing first OK. And No­var­tis’ is­sues with man­u­fac­tur­ing cell ther­a­pies ex­tend back to the sna­fus it ex­pe­ri­enced with late de­liv­ery to a small but sig­nif­i­cant group of pa­tients en­rolled in clin­i­cal tri­als.

At one stage in the de­vel­op­ment process, No­var­tis had a 6% fail­ure rate on the man­u­fac­tur­ing process in a key clin­i­cal tri­al, which they lat­er said was large­ly re­solved and brought down to 3%.

This morn­ing No­var­tis is fol­low­ing up with plans to in­vest €78.8 mil­lion in­to their cell and gene ther­a­py man­u­fac­tur­ing op­er­a­tions in Switzer­land in their lat­est stab at fix­ing the prob­lems.

But af­ter record­ing on­ly $16 mil­lion in sales for Q2, the big ques­tion loom­ing for No­var­tis is why pa­tients would want to take a risk with their ther­a­py if an­oth­er provider comes in­to the mar­ket which can do bet­ter on a com­plex task: ex­tract­ing T cells from pa­tients, mod­i­fy­ing them and then in­fus­ing pa­tients with a ther­a­peu­tic punch?

You can be sure that the top crew at Gilead and Kite — work­ing with a be­spoke man­u­fac­tur­ing site — are pay­ing close at­ten­tion.

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: 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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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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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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Gilead claims Tru­va­da patents in HHS’ com­plaint are in­valid

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.

Gilead dusts off a failed Ebo­la drug as coro­n­avirus spreads; Ex­elix­is boasts pos­i­tive Ph I/II da­ta

→ Less than a year ago Gilead’s antiviral remdesivir failed to make the cut as investigators considered a raft of potential drugs that could be used against an Ebola outbreak. But it may gain a new mission with the outbreak of the coronavirus in China, which is popping up now around the world.

Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.