Armed with up­dat­ed 24-week PhI­II da­ta, GBT con­vinces FDA to re­view sick­le cell drug un­der ac­cel­er­at­ed path­way

In yet an­oth­er sign of the FDA’s en­hanced flex­i­bil­i­ty un­der com­mis­sion­er Scott Got­tlieb, Glob­al Blood Ther­a­peu­tics $GBT has man­aged to con­vinced the reg­u­la­tor to al­low its ex­per­i­men­tal drug, vox­elo­tor, to be eval­u­at­ed un­der the ac­cel­er­at­ed ap­proval path­way for sick­le cell dis­ease (SCD), a group of in­her­it­ed red blood cell dis­or­ders that typ­i­cal­ly af­flict those of African an­ces­try.

SCD im­pacts he­mo­glo­bin, a pro­tein found in red blood cells that car­ries oxy­gen through­out the body, and is char­ac­ter­ized by episodes of sear­ing pain as well as or­gan dam­age.

On Mon­day, the San Fran­cis­co-based biotech said the FDA had agreed to let it ap­ply for vox­elo­tor’s ap­proval un­der this fast-track path­way on the ba­sis of its da­ta from an on­go­ing late-stage study that showed the drug was rais­ing he­mo­glo­bin lev­els, which the com­pa­ny deemed a re­li­able in­di­ca­tor that the once-dai­ly oral ther­a­py would like­ly re­duce the risk of stroke.

Vox­elo­tor is de­signed to work by in­creas­ing he­mo­glo­bin’s affin­i­ty for oxy­gen. SCD pa­tients have atyp­i­cal he­mo­glo­bin mol­e­cules, which can dis­tort red blood cells in­to a sick­le, or cres­cent, shape. Symp­toms such as ane­mia, re­peat­ed in­fec­tions and pe­ri­od­ic episodes of pain, be­gin to ap­pear in ear­ly child­hood. These episodes de­prive the body of oxy­gen-rich blood, which can cul­mi­nate in wide­spread tis­sue and or­gan dam­age, par­tic­u­lar­ly in the lungs, kid­neys, spleen, heart and brain, and dras­ti­cal­ly di­min­ish life ex­pectan­cy.

Ear­li­er this year, the com­pa­ny re­port­ed da­ta from the first tranche of its phase III HOPE study, which showed vox­elo­tor met the main goal of an im­prove­ment in he­mo­glo­bin greater than 1 g/dL with vox­elo­tor 1500 mg, com­pared with place­bo at 12 weeks. As part of ASH, the com­pa­ny pro­vid­ed up­dat­ed 24-week re­sults, which demon­strat­ed the drug con­ferred a sus­tained im­prove­ment in he­mo­glo­bin lev­els.

Da­ta showed that 65% of pa­tients tak­ing vox­elo­tor 1500 mg (p<0.0001) achieved a greater than 1 g/dL in­crease in he­mo­glo­bin at 24 weeks ver­sus 10% of pa­tients on the place­bo. Mean­while, 33% of pa­tients on the low­er 900 mg vox­elo­tor dose achieved (p=0.0159) a sim­i­lar in­crease in he­mo­glo­bin lev­els.

In ad­di­tion, vox­elo­tor ther­a­py was as­so­ci­at­ed with few­er va­so-oc­clu­sive crises (VOCs) – painful com­pli­ca­tions of SCD which oc­cur when sick­le shaped red blood cells get stuck in­side blood ves­sels – de­spite sub­stan­tial in­creas­es in he­mo­glo­bin.

The drug was well tol­er­at­ed with sim­i­lar safe­ty pro­files be­tween the two dos­es, and there was was no ev­i­dence of im­pair­ment of tis­sue oxy­gena­tion at ei­ther dose, the com­pa­ny said.

“These da­ta from the Phase 3 HOPE Study, in­clud­ing the clin­i­cal­ly mean­ing­ful and sta­tis­ti­cal­ly sig­nif­i­cant in­crease in he­mo­glo­bin, have been a key el­e­ment in the dis­cus­sions with the FDA which led to the agency’s agree­ment with GBT’s pro­pos­al for vox­elo­tor un­der the sub­part H ac­cel­er­at­ed ap­proval path­way,” GBT chief Ted Love said in a state­ment.

The com­pa­ny plans to re­quest a pre-NDA meet­ing for the first quar­ter of next year, it said on Mon­day. If ap­proved, it will con­duct a sep­a­rate study post-ap­proval to show the drug can de­fin­i­tive­ly re­duce the risk of stroke.

 

 

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Build­ing on suc­cess­ful PD-1 pact, Eli Lil­ly li­cens­es di­a­betes drug to Chi­nese part­ners at In­novent

Eli Lilly is expanding its partnership with China’s Innovent in a deal involving a diabetes drug sitting in its Phase I reserves.

The two companies had jointly developed one of China’s first homegrown PD-1 agents, scoring an approval for Tyvyt (sintilimab) late last year for relapsed/refractory classical Hodgkin’s lymphoma. This time around, Lilly is out-licensing a piece of its diabetes pipeline, a leading franchise that has historically produced the top-selling Trulicity and Humalog.

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.