In an un­usu­al move, ICER re­scinds draft re­port on JAK drugs for rheuma­toid arthri­tis to re­vise its mod­el­ing ap­proach

Two years ago, the In­sti­tute for Clin­i­cal and Eco­nom­ic Re­view (ICER) ad­mon­ished Ab­b­Vie for over­pric­ing the best-sell­ing drug in the world — Hu­mi­ra — along with the raft of ri­val drugs ap­proved for rheuma­toid arthri­tis. On Wednes­day, the in­flu­en­tial cost-ef­fec­tive­ness watch­dog re­scind­ed its draft re­port on the new crop of JAK in­hibitors, say­ing it was re­vis­it­ing the mod­el­ing ap­proach it em­ployed in the analy­sis pub­lished in late Sep­tem­ber.

The re­view en­com­passed Eli Lil­ly’s baric­i­tinib (brand­ed as Olu­mi­ant), Pfiz­er’s to­fac­i­tinib (sold as Xel­janz) and Ab­b­Vie’s re­cent­ly ap­proved upadac­i­tinib (chris­tened Rin­voq).

In the draft re­port, pub­lished Sep­tem­ber 26, ICER sought to eval­u­ate the cost-ef­fec­tive­ness of the three JAK in­hibitors ver­sus the es­tab­lished an­ti-TNF Hu­mi­ra (known chem­i­cal­ly as adal­i­mum­ab) — but found it could on­ly make the com­par­i­son with the new Ab­b­Vie treat­ment, due to a pauci­ty of com­para­tor da­ta on the oth­er two JAK treat­ments.

“Our base-case find­ings sug­gest that upadac­i­tinib pro­vides mar­gin­al clin­i­cal ben­e­fit in com­par­i­son to adal­i­mum­ab, at high­er costs. To­geth­er, these out­comes trans­late in­to cost-ef­fec­tive­ness es­ti­mates that ex­ceed com­mon­ly cit­ed cost-util­i­ty thresh­olds,” the re­view­ers wrote. “Re­sults from the in­di­rect mod­el­ing com­par­i­son of to­fac­i­tinib to adal­i­mum­ab sug­gest that for the mar­gin­al ben­e­fit to­fac­i­tinib of­fers, prices for this drug much high­er than the price of adal­i­mum­ab may not be jus­ti­fied.”

Then, on Wednes­day, ICER is­sued a brief state­ment sug­gest­ing it was reeval­u­at­ing the mod­el­ing ap­proach used in the draft ev­i­dence re­port. A new draft re­port will be pub­lished in the com­ing days, the agency said.

The un­usu­al move comes at a time when ICER is, in any case, re­assess­ing its meth­ods. In De­cem­ber, the in­sti­tute is ex­pect­ed to up­date the frame­work that un­der­pins its ev­i­dence re­ports on new drugs and oth­er health care in­ter­ven­tions. ICER last up­dat­ed its val­ue as­sess­ment frame­work in June 2017, and al­so cre­at­ed a fresh ap­proach to eval­u­at­ing ul­tra-rare or­phan drugs in No­vem­ber 2017.

In Ju­ly, the agency in its re­view of Duchenne mus­cu­lar dy­s­tro­phy treat­ments ac­knowl­edged it had used sig­nif­i­cant­ly high­er price es­ti­mates for two ther­a­pies in its mod­els — ver­sus the es­ti­mates used in their draft re­port in May. When queried by End­points News, ICER sug­gest­ed the num­bers used in the May re­port were in­cor­rect.

Akin to NICE in the UK, ICER is an in­de­pen­dent body that an­a­lyzes the cost-ef­fec­tive­ness of drugs and oth­er med­ical ser­vices in the Unit­ed States. Un­like NICE, though, ICER is not gov­ern­ment-af­fil­i­at­ed, but its de­ter­mi­na­tions are in­creas­ing­ly gain­ing trac­tion with pay­ers.

Each of the drugs re­viewed in the re­scind­ed re­port be­long to a fam­i­ly of med­i­cines called Janus ki­nase (JAK) in­hibitors — which have been plagued with safe­ty con­cerns. Named af­ter the two-faced Ro­man God Janus, the fam­i­ly con­sists of four en­zymes: JAK1, JAK2, JAK3 and TYK2, which are as­so­ci­at­ed with cy­tokine re­cep­tors on the sur­face of cells and form part of a path­way in­volved in in­flam­ma­to­ry and im­mune re­spons­es.

Pfiz­er’s JAK1/JAK3 in­hibitor — Xel­janz — has been blight­ed by reg­u­la­to­ry re­stric­tions af­ter the high­er dose of the block­buster drug was found to be as­so­ci­at­ed with the risk of blood clots and death. Lil­ly’s $LLY JAK1/JAK2 Olu­mi­ant, mean­while, was ini­tial­ly re­ject­ed by the US agency due to safe­ty con­cerns — on­ly to even­tu­al­ly se­cure ap­proval for the low­er dose. Lil­ly’s part­ner, In­cyte $IN­CY, elect­ed to walk away from co-fund­ing the drug’s de­vel­op­ment as fears about the ben­e­fit-risk pro­file of the class of drugs ac­cu­mu­lat­ed. In Au­gust, Ab­b­Vie’s $AB­BV JAK1 upadac­i­tinib was cleared by the FDA for rheuma­toid arthri­tis with a black box warn­ing.

Patrik Jonsson, the president of Lilly Bio-Medicines

Who knew? Der­mi­ra’s board kept watch as its stock price tracked Eli Lil­ly’s se­cret bid­ding on a $1.1B buy­out

In just 8 days, from December 6 to December 14, the stock jumped from $7.88 to $12.70 — just under the initial $13 bid. There was no hard news about the company that would explain a rise like that tracking closely to the bid offer, raising the obvious question of whether insider info has leaked out to traders.

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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
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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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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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.

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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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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