Io­n­is says it gath­ered promis­ing PhI­II da­ta for a top rare dis­ease drug, but se­ri­ous safe­ty ques­tions re­main

Io­n­is Phar­ma­ceu­ti­cals $IONS says that its Phase III study of in­ot­ersen (IO­N­IS-TTR­Rx) hit both pri­ma­ry end­points in pa­tients with rare cas­es of fa­mil­ial amy­loid polyneu­ropa­thy (FAP). But in­ves­ti­ga­tors al­so spelled out just how dan­ger­ous this drug can be, cloud­ing its fu­ture with reg­u­la­tors.

The FDA once put this drug on hold, caus­ing Glax­o­SmithK­line to edge away from their col­lab­o­ra­tion on the drug. But GSK still has an op­tion to grab mar­ket­ing rights on the ther­a­py, as Io­n­is push­es ahead with plans to file for an ap­proval.

The ef­fi­ca­cy da­ta weren’t spelled out in the com­pa­ny’s state­ment. But the safe­ty record was.

Dr. Morie Gertz

Re­searchers said that there were three se­ri­ous cas­es of throm­bo­cy­tope­nia, or low platelet lev­els, that were trig­gered by the drug. One of those pa­tients died from an in­tracra­nial he­m­or­rhage. There were al­so two se­ri­ous re­nal ad­verse events, and two oth­er pa­tients had to stop treat­ment fol­low­ing re­nal ob­ser­va­tions that raised in­ves­ti­ga­tors’ con­cerns.

That seemed to dic­tate the re­sponse among in­vestors as Io­n­is shares slid 10% in pre-mar­ket trad­ing.o140

On the pos­i­tive side, there was clear­ly pos­i­tive ef­fi­ca­cy da­ta on the Neu­ropa­thy Im­pair­ment Score +7 (mNIS+7) and the Nor­folk Qual­i­ty of Life Ques­tion­naire-Di­a­bet­ic Neu­ropa­thy over the 15-month study. That helps ex­plain why 95% of the 80% of pa­tients who com­plet­ed the study went on to con­tin­ue ther­a­py in the ex­ten­sion part of the tri­al.

Leerink’s Paul Mat­teis sized up the good, the bad and the ug­ly thus:

The ef­fi­ca­cy re­sults, which show a ben­e­fit on a dis­ease spe­cif­ic scale (mNIS+7) AND qual­i­ty-of-life, are bet­ter than in­vestor ex­pec­ta­tions as the Street was more cau­tious on the lat­ter mea­sure. How­ev­er, the safe­ty of TTR­rx re­mains a ma­jor ques­tion; IONS not­ed that “a de­tailed re­view of safe­ty da­ta from the study is on­go­ing”, and in the press re­lease, the com­pa­ny re­port­ed cas­es of se­ri­ous throm­bo­cy­tope­nia and a death due to in­tracra­nial he­m­or­rhage.

That could all play out to Al­ny­lam’s ben­e­fit. Its lead late-stage drug patisir­an could prove a safer al­ter­na­tive to Io­n­is’ drug, which is why the Cam­bridge-based biotech’s shares shot up 15% this morn­ing.

When the safe­ty is­sue first came up last year, trig­ger­ing the hold, GSK opt­ed to shelve plans for a Phase III study of TTR amy­loid car­diomy­opa­thy.

Transthyretin — or TTR — amy­loi­do­sis is char­ac­ter­ized by the grad­ual ac­cu­mu­la­tion of amy­loid in tis­sue and or­gans that lead to death.

Io­n­is’ stock was hit last week when an FDA warn­ing let­ter was cir­cu­lat­ed high­light­ing the case of an in­ves­ti­ga­tor in a sep­a­rate study who failed to prop­er­ly test platelet lev­els in pa­tients. Some of the an­a­lysts fol­low­ing the com­pa­ny not­ed that it raised some se­ri­ous is­sues on safe­ty re­lat­ed to its re­al-world use — how could physi­cians be ex­pect­ed to mon­i­tor platelet lev­els ef­fec­tive­ly if re­searchers don’t — and the stock, sub­ject to re­peat­ed short at­tacks, took a hit. That is­sue will like­ly to be close­ly con­sid­ered by reg­u­la­tors and out­side ex­perts dur­ing the drug re­view process.

“Fa­mil­ial amy­loid polyneu­ropa­thy is a dev­as­tat­ing ge­net­ic dis­ease that is painful and rapid­ly pro­gres­sive lead­ing to ear­ly death. The pos­i­tive re­sults from the NEU­RO-TTR study to­day are very en­cour­ag­ing for this un­der­served pa­tient pop­u­la­tion,” said  Dr. Morie Gertz, Di­vi­sion of Hema­tol­ogy, Roland Sei­dler Jr. Pro­fes­sor De­part­ment of Med­i­cine. “I have been treat­ing pa­tients with this dis­abling dis­ease for many years, and I am ex­cit­ed about the promise that in­ot­ersen holds to re­store their lives. I be­lieve in­ot­ersen has the po­ten­tial to trans­form the cur­rent stan­dard of care for pa­tients with TTR amy­loi­do­sis.”

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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