Blue­bird bio steps up with a promis­ing snap­shot of its gene ther­a­py up­grade

As a pi­o­neer in the new wave of gene ther­a­py treat­ments that have been steadi­ly wind­ing their way to­ward reg­u­la­tors with the promise of a once-and-done ge­net­ic fix for a wide range of ail­ments, blue­bird bio $BLUE al­so got the first taste of the kind of back­lash that can oc­cur when a new tech­nol­o­gy fails to live up to the hope and hype that spurs bil­lions of dol­lars of in­vest­ments.

David David­son

For blue­bird, that mo­ment of truth came a lit­tle more than two years ago, when the com­pa­ny re­port­ed that a hand­ful of pa­tients had in­ad­e­quate re­spons­es to its gene ther­a­py for sick­le cell dis­ease and be­ta-tha­lassemia. Com­pa­ny in­ves­ti­ga­tors went back to the draw­ing board, changed the man­u­fac­tur­ing process on Lenti­Glo­bin with a new ap­proach they had been work­ing on that they felt would de­liv­er a bet­ter gene ther­a­py. And to­day they un­wrapped a snap­shot of the im­pact they’ve had.

Bot­tom line: The first glimpse of hu­man da­ta looks promis­ing.

The first three pa­tients in blue­bird’s Phase III study for trans­fu­sion-de­pen­dent be­ta-tha­lassemia pa­tients of­fered some of the hu­man proof-of-con­cept da­ta they were look­ing for, mul­ti­ply­ing the num­ber of cells they were de­liv­er­ing with cor­rec­tive genes and pro­duc­ing a healthy flow of he­mo­glo­bin need­ed to cor­rect the dis­ease in the first pa­tient that was evalu­able at 6 months. Two oth­er pa­tients of­fered in­di­ca­tions of a sim­i­lar suc­cess — though one of the pa­tients al­so reg­is­tered a  pos­i­tive but low­er num­ber of vec­tor pos­i­tive cells than the oth­er two — leav­ing blue­bird ex­ecs hop­ing that they have the right po­ten­cy in place for a durable cure.

That un­even re­sponse took a quick bite out of blue­bird’s shares Fri­day morn­ing, slid­ing 6% in ear­ly trad­ing.

“This is an ex­cit­ing val­i­da­tion of the changes in the man­u­fac­tur­ing process,” says blue­bird CMO David David­son. He ex­plained: “We added two small mol­e­cule en­hancers – trans­duc­tion en­hancers – that we have been re­search­ing for many years, to find ways of in­creas­ing the ef­fi­cien­cy of the vi­ral vec­tor to en­ter and in­te­grate in­to stem cells.”

Here’s the slide on the first pa­tient’s re­sponse from blue­bird’s pre­sen­ta­tion at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion meet­ing in Madrid, which the biotech shared with me in a pre­view.

That 13.3 grams per deciliter col­umn on the right at 6 months in­cludes a sub­stan­tial amount of he­mo­glo­bin pro­duced specif­i­cal­ly by the ther­a­py af­ter trans­fu­sions were stopped.

It is, to be cer­tain, a tiny num­ber of pa­tients and there are no guar­an­tees in this busi­ness. But then blue­bird’s for­tunes in gene ther­a­py have al­ways been de­cid­ed by the re­spons­es of a hand­ful of pa­tients. Its piv­otal Phase III — da­ta from which will be de­liv­ered to the FDA along with an­oth­er late-stage tri­al— ini­tial­ly will re­cruit 15 adult and ado­les­cent pa­tients, then bring in 8 more chil­dren in an ex­ten­sion study. They’ll all be tracked for a con­sid­er­able amount of time as in­ves­ti­ga­tors look for any vari­a­tion in ef­fi­ca­cy and safe­ty.

Blue­bird still has a long ways to go and isn’t free of con­cerns on the safe­ty front. David­son al­so high­light­ed two pa­tients who were hos­pi­tal­ized af­ter ex­pe­ri­enc­ing acute gas­troen­teri­tis and acute chest syn­drome in their ear­li­er -205 study, though the com­pa­ny al­so be­lieves that in­ves­ti­ga­tors are in­creas­ing­ly con­fi­dent that they can avoid re­peats in the fu­ture.

So blue­bird takes an­oth­er step down the late-stage path­way, with plans to seek an ear­ly, con­di­tion­al ap­proval in Eu­rope based on the small ear­ly stud­ies it com­plet­ed.

“Eu­ro­pean reg­u­la­tors have been a lit­tle more cre­ative and more will­ing to ad­vance these ther­a­pies for­ward” than the FDA, David­son adds. But they are ad­vanc­ing on both fronts to­day.

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

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UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

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Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

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ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.

The key dates for KRAS watch­ers through the end of the year — the trail is nar­row and risks are ex­treme

There’s nothing quite like a big patent win when it comes to burnishing your prospects in the pipeline. And for Amgen, which seems to have rescued Enbrel for a run to 2029, the cheering section on Wall Street is now fixed on AMG 510 and a key rival.

And it didn’t take much data to do it. 

There was the first snapshot of a handful of patients, with a 50% response rate. Then came word that Amgen researchers are also tracking responses in different cancers, at least one in colorectal cancer and appendiceal too. 

Bain's Or­ly Mis­han joins Pfiz­er's neu­ro spin­out Cerev­el; On­colyt­ic virus biotech taps Sil­la­Jen ex­ec He­le­na Chaye as CEO

→ Bain Capital is deploying one of its top investors to Cerevel Therapeutics, steering a $350 million-plus neuro play carved out of Pfizer. Orly Mishan — a co-founder and principal of Bain’s life sciences unit — was involved in the partnership that birthed the biotech spinout in the first place. As Cerevel’s first chief business officer, she is tasked with corporate development, program management as well as technical operations. 

UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

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Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.