No­var­tis shoots for ear­ly OK of a ‘break­through’ blood can­cer drug af­ter re­vers­ing or­gan dam­age in tri­al

Up to now, No­var­tis’ mi­dostau­rin has been pri­mar­i­ly not­ed for its po­ten­tial in treat­ing a mu­ta­tion-spe­cif­ic type of acute myeloid leukemia, thrust in­to the spot­light af­ter the FDA hand­ed out its break­through des­ig­na­tion for the drug ear­li­er this year. But a new study shows that the drug al­so demon­strat­ed a sta­tis­ti­cal­ly sig­nif­i­cant abil­i­ty to halt and re­verse or­gan dam­age caused by rare cas­es of ad­vanced sys­temic mas­to­cy­to­sis. And the phar­ma gi­ant now plans to prep an ap­pli­ca­tion for reg­u­la­tors on both sides of the At­lantic in search of ear­ly mar­ket­ing ap­proval.

There are var­i­ous kinds of mas­to­cy­to­sis, which is char­ac­ter­ized by an over ac­cu­mu­la­tion of mast cells in tis­sue. But ad­vanced sys­temic mas­to­cy­to­sis threat­ens or­gan dam­age and death and one form – mast-cell leukemia – is in­vari­ably lethal.

Ja­son R. Gotlib, MD – Stan­ford Uni­ver­si­ty

“Mi­dostau­rin (PKC412) is a mul­ti­k­i­nase in­hibitor, so it has sev­er­al mol­e­c­u­lar tar­gets,” Ja­son Gotlib, the lead in­ves­ti­ga­tor from Stan­ford, tells me. That makes it right for AML pa­tients with a FLT-3 mu­ta­tion. It al­so in­hibits KIT D816V, a pro­tein in the ty­ro­sine ki­nase fam­i­ly which dri­ves the de­vel­op­ment of mast cells.

To test it, in­ves­ti­ga­tors re­cruit­ed 116 pa­tients in an open-la­bel study, with­out a con­trol arm, in­clud­ing 89 with dis­ease-re­lat­ed or­gan dam­age. 16 of the pa­tients had the most ag­gres­sive form of the dis­ease.

“Noth­ing works for them,” says Gotlib. But 8 of the 16 re­spond­ed to the drug and “7 had com­plete res­o­lu­tion of or­gan dam­age” as­so­ci­at­ed with longer sur­vival.

The over­all re­sponse rate Gotlib and his team tracked was 60%, with 45% of the pa­tients achiev­ing a “ma­jor re­sponse,” de­fined as  the com­plete res­o­lu­tion of at least one type of mas­to­cy­to­sis-re­lat­ed or­gan dam­age.

The me­di­an over­all sur­vival rate tracked in the study was 28.7 months, with the 16 mast-cell leukemia pa­tients achiev­ing a me­di­an OS rate of 9.4 months. But with­out a con­trol arm, there’s no way to de­ter­mine from this study if pa­tients gained a sur­vival ad­van­tage.

Even with­out a con­trol arm in the study, though, Gotlib says the im­pact on or­gan dam­age and the ab­sence of any ef­fec­tive ther­a­pies for the rare con­di­tion make it ap­pro­pri­ate to seek out ac­cel­er­at­ed ap­proval on the Phase II da­ta. And a spokesper­son for No­var­tis con­firmed that the Big Phar­ma play­er is al­so ready­ing its ap­pli­ca­tion for FLT-3 mu­tat­ed AML.

“This is a drug that works,” Dr. Robert Hro­mas from the Uni­ver­si­ty of Flori­da told the UPI. “And un­til now, we’ve re­al­ly had noth­ing.”

Hro­mas was not part of the study.

“Pa­tients with ad­vanced SM are part of a very small, high­ly un­der­served com­mu­ni­ty that has suf­fered from a lack of med­ical in­no­va­tion for many years,” said Alessan­dro Ri­va, the glob­al head of No­var­tis On­col­o­gy De­vel­op­ment and Med­ical Af­fairs. “No­var­tis…is now work­ing with reg­u­la­to­ry au­thor­i­ties to make mi­dostau­rin avail­able as quick­ly as pos­si­ble.”

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

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.”

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.