Bio­Marin lays out its PhI­II strat­e­gy for its close­ly-watched gene ther­a­py for he­mo­phil­ia A

Hen­ry Fuchs

When it comes to gene ther­a­py stud­ies, any­thing oth­er than a per­fect score al­ways rais­es a red flag about their fu­ture in late-stage test­ing. And no­body gets a per­fect score.

Bio­Marin was re­mind­ed of that les­son again to­day as it care­ful­ly laid out the lat­est promis­ing ear­ly-stage da­ta from a hand­ful of he­mo­phil­ia A pa­tients who re­ceived their gene ther­a­py BMN 270.

Their key da­ta were good to great. Ex­clud­ing one of the pa­tients in the high dose group, leav­ing 6 for analy­sis, the mean an­nu­al­ized bleed­ing rate was re­duced by 97% — from 16.3 to 0.5. “The me­di­an ABR for those same pa­tients was re­duced from 16.5 to ze­ro. The mean an­nu­al­ized Fac­tor VI­II in­fu­sions were re­duced by 94% from 136.7 to 8.5. The me­di­an an­nu­al­ized Fac­tor VI­II in­fu­sions were re­duced from 138.5 to ze­ro.” And the low­er, mid-range dose al­so demon­strat­ed an ex­cel­lent score on bleed­ing and in­fu­sion rates, with a drop to ze­ro.

So far, so good. Bio­Marin ex­ecs – which saw its shares $BM­RN climb about 2% — say they are ready to take the high dose in­to a Phase III study dur­ing the 4th quar­ter, plan­ning on a piv­otal pro­gram with few­er than 100 pa­tients.

But a few fac­tors caught an­a­lysts’ eyes in ex­am­in­ing the de­tailed break­down on the da­ta. One of the key is­sues was a wide vari­abil­i­ty in Fac­tor VI­II ex­pres­sion need­ed to keep he­mo­phil­ia in check. Joseph Schwartz at Leerink notes this morn­ing that in­vestors will look close­ly to see if reg­u­la­tors are con­cerned by the much-high­er-than-nor­mal lev­els of Fac­tor VI­II in some pa­tients be­fore ap­prov­ing the Phase III de­sign.

In­ter­est­ing­ly, there were al­so sev­er­al cas­es of el­e­vat­ed ala­nine amino­trans­ferase (ALT) re­quir­ing a ta­per­ing treat­ment of cor­ti­cos­teroids. At one point not long ago, that sort of re­ac­tion would rat­tle a con­sid­er­able num­ber of in­vestors. Now, it seems a com­mon and eas­i­ly man­aged side ef­fect with no ev­i­dence of de­rail­ing ther­a­py.

Just as Spark $ONCE is push­ing ahead with its he­mo­phil­ia B gene ther­a­py, Bio­Marin is look­ing to rev­o­lu­tion­ize ther­a­py in he­mo­phil­ia. A suc­cess in the loom­ing Phase II­Is for once-and-done treat­ments could put to rest a full slate of block­buster ther­a­pies com­pet­ing in this mar­ket. So look for plen­ty of care­ful da­ta crunch­ing in the months to come.

In the mean­time, Bio­Marin con­tin­ues to in­vest heav­i­ly in the work, com­plet­ing a man­u­fac­tur­ing fa­cil­i­ty for BMN 270.

Bio­Marin R&D chief Hank Fuchs laid out the stakes for pa­tients:

“We are striv­ing to make a big dif­fer­ence for pa­tients with se­vere he­mo­phil­ia A by de­vel­op­ing a treat­ment that not on­ly has the po­ten­tial to elim­i­nate bleeds, but al­so has the po­ten­tial to elim­i­nate the re­quire­ment for re­com­bi­nant Fac­tor VI­II in­fu­sions for he­mo­phil­ia A pa­tients re­lat­ed to trau­ma, surgery and day-to-day ac­tiv­i­ties.”

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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