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.



Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

UP­DAT­ED: In a land­mark first glimpse of hu­man da­ta from Ver­tex, CRISPR/Cas9 gene ther­a­py sig­nals ear­ly ben­e­fit

Preliminary data on two patients with blood disorders that have been administered with Vertex and partner CRISPR Therapeutics’ gene-editing therapy suggest the technology is safe and effective, marking the first instance of the benefit of the use of CRISPR/Cas9 technology in humans suffering from disease.

Patients in these phase I/II studies give up peripheral blood from which hematopoietic stem and progenitor cells are isolated. The cells are tinkered with using CRISPR/Cas9 technology, and the edited cells — CTX001 — are infused back into the patient via a stem cell transplant. The objective of CTX001 is to fix the errant hemoglobin gene in patents with two blood disorders: beta-thalassemia and sickle cell disease, by unleashing the production of fetal hemoglobin.

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UP­DAT­ED: Make that 2 ap­proved RNAi drugs at Al­ny­lam af­ter the FDA of­fers a speedy OK on ul­tra-rare dis­ease drug

Seventeen years into the game, Alnylam’s pivot into commercial operations is picking up speed.
The bellwether biotech $ALNY has nabbed their second FDA OK for an RNAi drug, this time for givosiran, the only therapy now approved for acute hepatic porphyria. This second approval came months ahead of the February deadline — even after winning priority review following their ‘breakthrough’ title earlier.
AHP is an extremely rare disease, with some 3,000 patients in Europe and the US, not all diagnosed, and analysts have projected peak revenue of $600 million to $700 million a year. The drug will be sold as Givlaari.

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David Ricks. Eli Lilly

Eli Lil­ly touts $400M man­u­fac­tur­ing ex­pan­sion, 100 new jobs to much fan­fare in In­di­anapo­lis — even though it's been chop­ping staff

Eli Lilly is pouring in $400 million to beef up manufacturing facilities at its home base of Indianapolis. The investment, which was lauded by the city’s mayor, is expected to create 100 new jobs.

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Am­gen chops 172 more staffers in R&D, op­er­a­tions and sales amid neu­ro­science ex­it, rev­enue down­turn

Neuroscience wasn’t the only unit that’s being hit by a reorganization underway at Amgen. As well as axing 149 employees in its Cambridge office, the company has disclosed that 172 others nationwide, including some from its Thousand Oaks, CA headquarters, are being let go.

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Stephen Hahn (via Senate HELP Committee)

Stephen Hahn gets through Sen­ate’s soft­ball job in­ter­view — but most­ly plays dodge­ball on the is­sues fac­ing the FDA

Anyone looking for fresh insights on what kind of FDA commissioner Stephen Hahn will be got precious few clues during Wednesday’s Senate hearing on the nomination.

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Op­di­vo/Yer­voy com­bo for melanoma fails in key pa­tient pop­u­la­tion

Bristol-Myers Squibb’s efforts to expand their checkpoint inhibitor combination have run into another recalcitrant cancer.

The NJ-based pharma announced that a combination of Yervoy and Opdivo didn’t beat out Opdivo alone in patients with resected high-risk melanoma who had very low levels of PD-L1. The drug combo couldn’t improve recurrence-free survival in these post-surgery patients.

Ver­tex's stel­lar quar­ter car­ries on with French re­im­burse­ment deal

Vertex’s golden quarter just got brighter. About a month after the US drugmaker finally clinched a deal with UK authorities to cover its slate of cystic fibrosis (CF) drugs following years of protracted negotiations, the company on Wednesday secured a deal with France for its CF therapy, Orkambi.

After the UK, France has one of the largest CF populations outside the United States. Achieving French reimbursement unlocks an ~7000-patient CF population, around ~2500-3000 of which will likely be eligible to receive (and be reimbursed for) Orkambi, Stifel’s Paul Matteis wrote in a note.

Nello Mainolfi, Kymera via Youtube

Kymera hands the helm to No­var­tis vet — and found­ing CSO — Nel­lo Main­olfi

Kymera Therapeutics is turning to a co-founder to run the company.
The protein degradation specialist with a deep-pocket syndicate behind them has opted to give the helm officially to Nello Mainolfi. The new CEO is a veteran of the Novartis Institutes for Biomedical Research. He joined Atlas Venture in their entrepreneur-in-residence program and helped launch Kymera as the CSO three years ago with Atlas’ Bruce Booth.
The boast at Kymera is that they’re angling to create a new class of protein degraders, a popular field where there’s been a variety of startups. One of its chief advocates is NIBR head Jay Bradner, who launched C4 just ahead of joining Novartis, where he’s also been doing new work in the field.