Nick Leschly, bluebird CEO (Jeff Rumans/JPM20)

Lenti­Glo­bin con­tin­ues to de­liv­er in lat­est sick­le cell up­date as blue­bird out­lines path to ac­cel­er­at­ed ap­proval, de­spite pa­tient death

Still reel­ing from the FDA’s stun­ning re­fusal to file its CAR-T ther­a­py ide-cel, blue­bird is ea­ger to win back some cred­i­bil­i­ty with a new slice of the Lenti­Glo­bin da­ta they will be tak­ing to the FDA for an ac­cel­er­at­ed ap­proval.

To be sure, the BLA sub­mis­sion won’t hap­pen un­til the sec­ond half of 2021 — giv­ing blue­bird plen­ty of time to fig­ure out the man­u­fac­tur­ing. But an up­date pre­sent­ed at the EHA vir­tu­al con­gress has ap­par­ent­ly helped them reach “gen­er­al agree­ment” with reg­u­la­tors and boost­ed ex­ecs’ con­fi­dence.

Build­ing on pre­vi­ous­ly re­port­ed da­ta, the pre­sen­ta­tion cen­ters around Group C of the HGB-206 study, com­pris­ing a to­tal of 25 pa­tients who re­ceived a gene ther­a­py pro­duced on a “re­fined man­u­fac­tur­ing process that was de­signed to in­crease vec­tor copy num­ber (VCN) and im­prove en­graft­ment po­ten­tial of gene-mod­i­fied stem cells.”

Among 14 pa­tients with at least six months of fol­low-up and a his­to­ry of va­so-oc­clu­sive crises and acute chest syn­drome — five more than the last dis­clo­sure — the mean re­duc­tion in an­nu­al­ized rate of those painful episodes was 99.5%. It marks a slight im­prove­ment from the al­ready stel­lar 99% in­ves­ti­ga­tors ob­served at ASH last De­cem­ber.

These were pa­tients who had a me­di­an of eight events in the two years pri­or to treat­ment, ac­cord­ing to blue­bird.

One of the pa­tients who had com­plete res­o­lu­tion of va­so-oc­clu­sive events died sud­den­ly 20 months af­ter treat­ment, al­though it was at­trib­uted to car­dio­vas­cu­lar and oth­er un­der­ly­ing is­sues and thus deemed “un­like­ly re­lat­ed” to Lenti­Glo­bin.

Zoom­ing out to the 16 who made the six-month cut­off point, me­di­an lev­els of a key bio­mark­er known as gene ther­a­py-de­rived he­mo­glo­bin were main­tained and con­tributed at least 40% of all he­mo­glo­bin.

At last vis­it re­port­ed, to­tal he­mo­glo­bin ranged from 9.6 – 16.2 g/dL and HbAT87Q lev­els ranged from 2.7 – 9.4 g/dL. At Month 6 the pro­duc­tion of HbAT87Q was as­so­ci­at­ed with a re­duc­tion in the pro­por­tion of HbS in to­tal he­mo­glo­bin. Pa­tients had a me­di­an of ≤ 60% HbS. All pa­tients in Group C were able to stop reg­u­lar blood trans­fu­sions and re­main off trans­fu­sions at three months post-treat­ment.

What mat­ters most, though, will be the rate of com­plete res­o­lu­tion of se­vere va­so-oc­clu­sive events at 18 months post-treat­ment — which blue­bird said would ce­ment the planned BLA sub­mis­sion.

Then there’s the com­mer­cial man­u­fac­tur­ing is­sues that led to pre­vi­ous de­lays for the launch of its oth­er EU-ap­proved gene ther­a­py, Zyn­te­glo, and re­view of ide-cel.

In an earn­ings call last month, CEO Nick Leschly promised an­a­lysts that they have “learned a lot” and are pre­pared for the tran­si­tions in­to new pro­duc­tion meth­ods, in­clud­ing sus­pen­sion lentivi­ral vec­tor. “(Q)uite hon­est­ly, we would not be sign­ing up for a reg­u­la­to­ry time line or range of time line if we didn’t feel that we had the ex­e­cu­tion in­fra­struc­ture be­hind it,” he said.

Lina Gugucheva, NewAmsterdam Pharma CBO

Phar­ma group bets up to $1B-plus on the PhI­II res­ur­rec­tion of a once dead-and-buried LDL drug

Close to 5 years after then-Amgen R&D chief Sean Harper tamped the last spade of dirt on the last broadly focused CETP cholesterol drug — burying their $300 million upfront and the few remaining hopes for the class with it — the therapy has been fully resurrected. And today, the NewAmsterdam Pharma crew that did the Lazarus treatment on obicetrapib is taking another big step on the comeback trail with a €1 billion-plus regional licensing deal, complete with close to $150 million in upfront cash.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

How pre­pared is bio­phar­ma for the cy­ber dooms­day?

One of the largest cyberattacks in history happened on a Friday, Eric Perakslis distinctly remembers.

Perakslis, who was head of Takeda’s R&D Data Sciences Institute and visiting faculty at Harvard Medical School at the time, had spent that morning completing a review on cybersecurity for the British Medical Journal. Moments after he turned it in, he heard back from the editor: “Have you heard what’s going on right now?”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Matt Gline, Roivant CEO (John Sciulli/Getty Images for GLG)

Roivant chops sick­le cell gene ther­a­py, der­ma­tol­ogy drugs to fo­cus on 'high­er val­ue pro­ject­s'

Roivant is sweeping a suite of drugs, including a gene therapy for sickle cell disease already in the clinic, out of its pipeline.

Six programs from four of its “vants” are being wound down as part of “a company-wide cost optimization and pipeline reprioritization initiative to reduce our expected operating expenses and prioritize our capital resources.”

When reached by Endpoints News, a spokesperson said, “We don’t anticipate a material reduction in headcount but we will likely reassign some folks to higher value projects as part of winding down specific programs.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Laurence Reid, Decibel CEO

Still in pre­clin­i­cal test­ing for ear gene ther­a­pies, Deci­bel touts small snap­shot of chemo-in­duced hear­ing loss drug

Though Decibel Therapeutics has largely pivoted toward gene therapies for the inner ear, its lead clinical candidate simply aims to protect cancer patients from chemotherapy-induced hearing loss. On Tuesday, the biotech presented its first efficacy data for the program, and execs like what they see.

Decibel reported interim results from a Phase Ib study showing the experimental drug, dubbed DB-020, largely protected a small group of patients from losing their hearing. Researchers used a particularly unique study design, administering the compound in one of each patients’ ears before they received cisplatin chemotherapy and placebo in the other.

Pearl Huang, Dunad Therapeutics CEO (Ken Richardson, PR Newswire)

Long­time biotech leader Pearl Huang takes the reins as CEO of No­var­tis-backed up­start

It has only been a few months since Pearl Huang exited the top seat at Cygnal Therapeutics, but now she’s back at the helm of another biotech.

After taking a few months off — passing an exam in that time to get her captain’s license from the US Coast Guard — she’s been named CEO of Dunad Therapeutics, a biotech focused on developing a small molecule covalent therapies that was founded in 2020. Huang told Endpoints News that two factors attracted her to going back to the c-suite: the company’s technology and its co-founders.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Deborah Dunsire, Lundbeck CEO

Af­ter a 5-year re­peat PhI­II so­journ, Lund­beck and Ot­su­ka say they're fi­nal­ly ready to pur­sue OK to use Rex­ul­ti against Alzheimer's ag­i­ta­tion

Five years after Lundbeck and their longtime collaborators at Otsuka turned up a mixed set of Phase III data for Rexulti as a treatment for Alzheimer’s dementia-related agitation, they’ve come through with a new pivotal trial success they believe will finally put them on the road to an approval at the FDA. And if they’re right, some analysts believe they’re a short step away from adding more than $500 million in annual sales for the drug, already approved in depression and schizophrenia.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Chris Anzalone, Arrowhead CEO

Take­da, Ar­row­head spot­light da­ta from small tri­al show­ing RNAi works in a rare liv­er con­di­tion

Almost two years after Takeda wagered $300 million cash to partner with Arrowhead on an RNAi therapy for a rare disease, the companies are spelling out Phase II data that they believe put them one step closer to their big dreams.

In a small, open label study involving only 16 patients who had liver disease associated with alpha-1 antitrypsin deficiency (AATD), Arrowhead’s candidate — fazirsiran, previously ARO-AAT — spurred substantial reductions in accumulated mutant AAT protein in the liver, a hallmark of the condition. Investigators also tracked improvements in symptoms, with seven out of 12 who received the high, 200 mg dose seeing regression of liver fibrosis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,400+ biopharma pros reading Endpoints daily — and it's free.

Ben Zimmer, Priovant CEO

Roivant un­veils lat­est spin­out as Pfiz­er en­trusts JAK1/TYK2 to Pri­o­vant

In November, Pfizer disclosed it’s spun out the Phase II dual JAK1/TYK2 inhibitor to a startup formed in collaboration with an unnamed, experienced partner.

We now know who the partner is. And as Pfizer and Roivant officially take the wraps off Priovant Therapeutics, the companies reveal that they have started two registrational trials of the drug, brepocitinib, as part of a broader plan to develop a big, first-in-class franchise spanning multiple orphan and specialty autoimmune diseases.