Gilead scores a TKO with PhI­II fil­go­tinib da­ta, but still faces some big bouts — and doubts — ahead

Gilead’s new Phase III rheuma­toid arthri­tis da­ta on its JAK1 in­hibitor fil­go­tinib have sparked a huz­zah from the cheer­ing sec­tion of Wall Street an­a­lysts, but there re­main plen­ty of unan­swered ques­tions about the fu­ture of this ther­a­py.

Thurs­day night the big biotech post­ed pos­i­tive da­ta from 2 Phase III stud­ies out­lin­ing a new batch of pos­i­tive ef­fi­ca­cy and safe­ty scores need­ed for an ap­proval of this drug — its oth­er and now even more close­ly watched big late-stage drug in the wake of their selon­sert­ib mis­fire in NASH. But while the drug beat out place­bo hand­i­ly, Gilead has a much high­er mark to hit in a fast-chang­ing field.

The news was a sol­id pos­i­tive for Gilead’s part­ners at Gala­pa­gos $GLPG, though, which saw its stock shoot up 13% on the re­leas­es. Gilead shares were up 2.7% af­ter the bell.

At this point, the more cau­tious ob­servers be­lieve that Gilead may well have a com­pet­i­tive play­er in the field, but the back-to-back pos­i­tive Phase II­Is are no clear-the-bases home run.

A num­ber of an­a­lysts spot­light­ed the new FINCH 1 and FINCH 3 re­sults, with ACR20/50/70 re­sults that over­shad­owed the sug­ar pill re­sponse lev­els as well as a methotrex­ate arm. But their low 100 mg da­ta were al­so gen­er­al­ly in line with Ab­b­Vie’s Hu­mi­ra, set to lose patent pro­tec­tion no lat­er than 2023. And the 200 mg da­ta, while out­per­form­ing Hu­mi­ra, is al­so go­ing to be heav­i­ly scru­ti­nized by reg­u­la­tors alarmed by the se­ri­ous safe­ty is­sues posed by high­er dos­es of the JAK in­hibitors on the mar­ket.

The FDA and EMA both is­sued stark warn­ings re­cent­ly about the dan­gers posed by 10 mg Xel­janz, and Eli Lil­ly was de­nied an ap­proval on the high dose of Olu­mi­ant — af­ter the drug was ini­tial­ly re­ject­ed out­right. And while Gilead re­searchers helped ad­dress the most im­me­di­ate con­cerns about safe­ty with new late-stage da­ta to sup­port the drug’s safe­ty pro­file, the ju­ry will like­ly re­main out on that score.

Bri­an Sko­r­ney

Baird’s Bri­an Sko­r­ney was gen­er­al­ly pleased, but not quite ready to call this an out­right win.

Da­ta re­leased from the FINCH 1 and 3 tri­als of fil­go­tinib in RA show that the med­ica­tion has sim­i­lar ef­fi­ca­cy to Ab­b­Vie’s up­atic­i­tinib. Clean safe­ty should help al­le­vi­ate in­vestor con­cerns sur­round­ing pri­or hic­cups seen with oth­er JAK in­hibitors, as fil­go­tinib was shown to have nu­mer­i­cal­ly low­er rates of CV events as com­pared to place­bo. 

Sko­r­ney is re­serv­ing fi­nal judg­ment un­til he sees da­ta from the MAN­TA study. But the com­pa­ny re­mains in the game for com­pet­ing with Ab­b­Vie, which has dom­i­nat­ed the space for years with its $20 bil­lion drug and next-gen ap­proach.

Jef­feries’ Michael Yee was en­thu­si­as­tic, but al­so con­ced­ed:

We ac­knowl­edge that a key over­hang is the on­go­ing male tox­i­c­i­ty study (MAN­TA), but it could have in­ter­im da­ta in Q3:19 and lead to a faster-than-ex­pect­ed fil­ing short­ly there­after (e.g. file on in­ter­im rather than tri­al com­ple­tion in 2020). Fil­ings are pend­ing post dis­cus­sions with FDA.

Tyler Van Bu­ren

Piper Jaf­fray’s Tyler Van Bu­ren wasn’t call­ing this a best-in-class drug, but he still sees block­buster po­ten­tial in a huge mar­ket.

The mag­ni­tude of the var­i­ous ACR20 treat­ment ben­e­fits ob­served in FINCH1 and FINCH3…are nu­mer­i­cal­ly low­er than tri­al re­sults from com­pet­i­tive agents. How­ev­er, we note that these cross-tri­al com­par­isons are fraught with er­ror and like­ly af­fect­ed by the rel­a­tive high place­bo/MTX rates in the FINCH tri­als. With re­spect to safe­ty, the in­ci­dence of SAEs – in­clud­ing DVTs – ap­pears rel­a­tive­ly low when com­par­ing the events/100 pa­tient years to the reg­is­tra­tional Xel­janz da­ta. All in all, fil­go­tinib ap­pears to be an ef­fec­tive, safe, and com­pet­i­tive oral JAK in­hibitor and we con­tin­ue to mod­el a launch in 2021 with sales sur­pass­ing $1.5B by 2028. Our big­ger con­cerns are (1) if a fil­go­tinib launch can re­al­ly oc­cur in 2021 (giv­en that Man­ta study com­ple­tion is re­quired and tim­ing is un­cer­tain) and (2) the com­pet­i­tive dy­nam­ics when launched as it is the fourth oral JAK to mar­ket.

Gilead still has lots of work to do on this pro­gram, and suc­cess won’t come eas­i­ly.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,100+ biopharma pros reading Endpoints daily — and it's free.

Game on: Re­gen­eron's BC­MA bis­pe­cif­ic makes clin­i­cal da­ta de­but, kick­ing off mul­ti­ple myelo­ma matchup with Bris­tol-My­ers

As J&J attempts to jostle past Bristol-Myers Squibb and bluebird for a landmark approval of its anti-BCMA CAR-T — and while GlaxoSmithKline maps a quick path to the FDA riding on its own BCMA-targeting antibody-drug conjugates — the bispecifics are arriving on the scene to stake a claim for a market that could cross $10 billion per year.

The main rivalry in multiple myeloma is shaping up to be one between Regeneron and Bristol-Myers, which picked up a bispecific antibody to BCMA through its recently closed $74 billion takeover of Celgene. Both presented promising first-in-human data at the ASH 2019 meeting.

FDA lifts hold on Abeon­a's but­ter­fly dis­ease ther­a­py, paving way for piv­otal study

It’s been a difficult few years for gene and cell therapy startup Abeona Therapeutics. Its newly crowned chief Carsten Thiel was forced out last year following accusations of unspecified “personal misconduct,” and this September, the FDA imposed a clinical hold on its therapy for a form of “butterfly” disease. But things are beginning to perk up. On Monday, the company said the regulator had lifted its hold and the experimental therapy is now set to be evaluated in a late-stage study.

Paul Hudson. Sanofi

New Sanofi CEO Hud­son adds next-gen can­cer drug tech to the R&D quest, buy­ing Syn­thorx for $2.5B

When Paul Hudson lays out his R&D vision for Sanofi tomorrow, he will have a new slate of interleukin therapies and a synthetic biology platform to boast about.

The French pharma giant announced early Monday that it is snagging San Diego biotech Synthorx in a $2.5 billion deal. That marks an affordable bolt-on for Sanofi but a considerable return for Synthorx backers, including Avalon, RA Capital and OrbiMed: At $68 per share, the price represents a 172% premium to Friday’s closing.

Synthorx’s take on alternative IL-2 drugs for both cancer and autoimmune disorders — enabled by a synthetic DNA base pair pioneered by Scripps professor Floyd Romesberg — “fits perfectly” with the kind of innovation that he wants at Sanofi, Hudson said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,100+ biopharma pros reading Endpoints daily — and it's free.

Roche faces an­oth­er de­lay in strug­gle to nav­i­gate Spark deal past reg­u­la­tors — but this one is very short

Roche today issued the latest in a long string of delays of its $4.3 billion buyout of Philadelphia-based Spark Therapeutics. The delay comes as little surprise — it is their 10th in as many months — as their most recent delay was scheduled to expire before a key regulatory deadline.

But it is notable for its length: 6 days.

Previous extensions had moved the goalposts by about 3 weeks to a month, with the latest on November 22 expiring tomorrow. The new delay sets a deadline for next Monday, December 16, the same day by which the UK Competition and Markets Authority has to give its initial ruling on the deal. And they already reportedly have lined up an OK from the FTC staff – although that’s only one level of a multi-step process.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,100+ biopharma pros reading Endpoints daily — and it's free.

KalVis­ta's di­a­bet­ic mac­u­lar ede­ma da­ta falls short — will Mer­ck walk away?

Merck’s 2017 bet on KalVista Pharmaceuticals may have soured, after the UK/US-based biotech’s lead drug failed a mid-stage study in patients with diabetic macular edema (DME).

Two doses of the intravitreal injection, KVD001, were tested against a placebo in a 129-patient trial. Patients who continued to experience significant inflammation and diminished visual acuity, despite anti-VEGF therapy, were recruited to the trial. Typically patients with DME — the most frequent cause of vision loss related to diabetes — are treated with anti-VEGF therapies such as Regeneron’s flagship Eylea or Roche’s Avastin and Lucentis.

UP­DAT­ED: Ob­sE­va makes case for best-in-class hor­mone sup­pres­sive ther­a­py in pos­i­tive uter­ine fi­broid study

About a month after the Swiss biotech disclosed a failed late-stage study in its IVF program, ObsEva on Monday unveiled positive pivotal data on its experimental treatment for heavy menstrual bleeding triggered by uterine fibroids.

ObsEva in-licensed the drug, linzagolix, from Japan’s Kissei Pharmaceutical in 2015. Two doses of the drug (100 mg and 200 mg) were tested against a placebo in the 535-patient Phase III study, dubbed PRIMROSE 2, in patients who were both on and off hormonal add-back therapy (ABT).

Ear­ly-stage can­cer biotech nails $85M C round; Flem­ming Orn­skov's Gal­der­ma scores 'break­through' sta­tus

→ Zentalis Pharmaceuticals just nabbed an $85 million round from a syndicate that includes Matrix Capital, Viking Global Investors, Redmile Group, Farallon Capital, Perceptive Advisors, Surveyor Capital and Eventide Asset Management. Their lead drug is ZN-c5, which is currently in Phase I/II trials. The biotech describes that drug as a “potential best-in-class oral Selective Estrogen Receptor Degrader for estrogen receptor-positive, HER2-negative (ER+/ HER2-) breast cancer.”