FDA slaps a hold on Agios’ PK drug, forc­ing the biotech to kill it in fa­vor of an in­ter­nal ri­val

Agios CEO David Schenkein

A few days ago, Agios $AGIO was try­ing to de­cide whether it should take AG-348 or AG-519 in­to a piv­otal tri­al for rare cas­es of pyru­vate ki­nase (PK) de­fi­cien­cy. But now the FDA has made the de­ci­sion for Agios, hand­ing down a clin­i­cal hold on AG-519 that per­suad­ed the biotech to scrap the pro­gram al­to­geth­er.

The hold, Agios CEO David Schenkein tells me, was trig­gered by an ear­li­er case of cholesta­t­ic he­pati­tis that was re­port­ed at ASH a lit­tle more than a week ago. One of the pa­tients in a bioavail­abil­i­ty study tak­ing a 300 mg dose was hit by the liv­er dis­ease. And even though “she’s im­prov­ing” while Agios was al­so “like­ly to move to 50 mg or low­er (for the piv­otal), one can’t be sure we wouldn’t have seen this again.”

That case of cholesta­t­ic he­pati­tis — which can dam­age the liv­er — rat­tled in­vestors at the time, bad­ly dent­ing the biotech’s shares. And Agios took a 20% hit on its share price in af­ter-mar­ket trad­ing to­day.

AG-348 has more da­ta, but an­a­lysts have been ques­tion­ing whether a more po­tent 519 could make for a bet­ter gam­ble than a drug with a wan­ing im­pact. In­ves­ti­ga­tors al­so record­ed ev­i­dence of aro­matase in­hi­bi­tion for AG-348, says Schenkein, but with­out clin­i­cal im­pact. AG-348, he adds, “is a ter­rif­ic drug with com­pelling da­ta.”

It al­so has the kind of risk/ben­e­fit pro­file that is worth a piv­otal gam­ble, he adds, as op­posed to what they have now in 519. Not all an­a­lysts are like­ly to buy off on that with­out ques­tion.

“Fol­low-on com­pound AG-519 ap­pears to be slight­ly more po­tent, at least based on phar­ma­co­dy­nam­ics (PD) mark­ers while lack­ing aro­matase in­hi­bi­tion of AG-348,” not­ed Leerink’s Michael Schmidt in an ASH up­date, as Agios shares slid on the re­ac­tion. “One drug-re­lat­ed se­ri­ous ad­verse event (SAE) of cholesta­t­ic he­pati­tis at a high dose lev­el is be­ing in­ves­ti­gat­ed, but the dose ex­pect­ed to move in­to Ph III is ex­pect­ed to be sig­nif­i­cant­ly low­er ac­cord­ing to mgmt.”

PK de­fi­cien­cy is a rare in­her­it­ed dis­ease that trig­gers the ac­cel­er­at­ed de­struc­tion of red blood cells. The biotech’s lead pro­grams are AG-120 and AG-220 for can­cers with IDH1 and IDH2 mu­ta­tions.

“We share the FDA’s com­mit­ment to pa­tient safe­ty and be­lieve this is the right de­ci­sion to ul­ti­mate­ly help peo­ple with PK de­fi­cien­cy,” said Schenkein in a state­ment. “As the lead com­pound in our PKR pro­gram, AG-348 has demon­strat­ed clear proof of con­cept with ro­bust, rapid and sus­tained in­creas­es in he­mo­glo­bin in pa­tients with PK de­fi­cien­cy. Based on our clin­i­cal ex­pe­ri­ence with DRI­VE PK, we are de­vel­op­ing a reg­is­tra­tion path for AG- 348 in adult PK de­fi­cien­cy pa­tients and plan to dis­cuss this strat­e­gy with reg­u­la­tors.”

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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