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.

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

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Vas Narasimhan. Getty Images

UP­DAT­ED: Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and briefly spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

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UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

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IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The researcher behind base-editing is out with what some scientists are hailing as the biggest advancement in CRISPR technology since that 2016 breakthrough: “prime editing.” The new molecular gadget is capable of erasing any base pair and stenciling in another and cutting or adding long segments of DNA without breaking both strands of the helix.

David Liu, base editing pioneer and founder of Beam Therapeutics, published the findings in Nature alongside Andrew Anzalone. They estimated that the breakthrough “in principle” puts 89% of human diseases in purview — although experts cautioned that human therapies were a long way off.

Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

For the past three years Frazier Healthcare Partners’ Bhaskar Chaudhuri has been carefully and quietly grooming Arcutis Therapeutics, a new dermatology play he co-founded to deliver topical formulations of well-known drugs. Now that the biotech is poised to enter Phase III, he’s being joined by a marquee syndicate for its $94.5 million Series C.

HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

UP­DAT­ED: Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.