As car­dio R&D shrinks in size, a new study high­lights some se­ri­ous pit­falls – and a pos­i­tive shift

In biotech cir­cles, it’s be­come an ar­ti­cle of faith that can­cer of­fers some of the best prospects in new drug de­vel­op­ment. Car­di­ol­o­gy, mean­while, looks like a long, ex­pen­sive and risky prospect. And a new study now un­der­scores the im­pact that shift in at­ti­tude has had, while spot­light­ing a solid­ly up­beat mi­gra­tion to a new gen­er­a­tion of ther­a­pies look­ing to carve out some nov­el re­sults as me-too drugs are rel­e­gat­ed to the side­lines. The au­thors, in­clud­ing Aaron Kessel­heim at Brigham and Women’s, al­so call out de­vel­op­ers for fail­ing to pub­lish the re­sults of failed stud­ies.

The re­searchers looked at 347 car­dio drugs that en­tered the clin­ic be­tween 1990 and 2012. From 1990 to 1995, car­dio drugs ac­count­ed for 108 of 679 Phase I stud­ies – a to­tal of 16%. But be­tween 2005 and 2012, the per­cent­age fig­ure shrank to on­ly 5%, ac­count­ing for 125 of 2,366 ear­ly stage projects go­ing in­to the clin­ic. In 1990, 21% of all Phase III stud­ies were in car­dio, com­pared to on­ly 7% in 2012.

Among oth­er things, this study al­so in­di­cates just how much big­ger the over­all in­dus­try pipeline is these days. The study was pub­lished in the Aug. 29 is­sue of the jour­nal JACC: Ba­sic to Trans­la­tion­al Sci­ence.

Caus­es for Car­dio Drugs Be­ing Dis­con­tin­ued in Phase 3

Not sur­pris­ing­ly, car­dio is dom­i­nat­ed by Big Phar­ma, which has the deep pock­ets to see a new drug in this field through late-stage stud­ies that can of­fer re­quire thou­sands of pa­tients. Here’s the bot­tom line:

“Over­all, small and medi­um-sized com­pa­nies ac­count­ed for 43% of new Phase 1 tri­als for car­dio­vas­cu­lar drugs, 38% of new Phase 2 tri­als, and 31% of new Phase 3 tri­als. In all three phas­es, the pro­por­tion of car­dio­vas­cu­lar tri­als start­ed by small and medi­um-sized com­pa­nies was sig­nif­i­cant­ly small­er than that for non­car­dio­vas­cu­lar tri­als.”

And for both large and small com­pa­nies, the fo­cus has shift­ed from me-too drugs to nov­el ther­a­peu­tics. Back in 1990, 27% of the car­dio drugs in Phase III were cat­e­go­rized as nov­el en­ti­ties, com­pared to 57% in 2012.

Track­ing 54 late-stage car­dio drugs that were dis­con­tin­ued, 44% were scut­tled due to a lack of ef­fi­ca­cy, with 24% tor­pe­doed by safe­ty is­sues. And some of those safe­ty is­sues were linked to a high­er death rate in the drug arm. But car­dio, they add, is not par­tic­u­lar­ly more risky than any oth­er field in R&D. One big prob­lem about the piv­otal fail­ures, the re­searchers add, is that da­ta are fre­quent­ly nev­er pub­lished, leav­ing in­ves­ti­ga­tors in the field in the fog about what went wrong and how to avoid ear­li­er mis­takes.

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.

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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