Blue­bird’s gene ther­a­py for be­ta-tha­lassemia falls short of a cure, but still wows in 22 pa­tients

Af­ter go­ing back to the draw­ing board to come up with a bet­ter gene ther­a­py for be­ta-tha­lassemia, a dis­ease that in­ter­feres with the body’s abil­i­ty to pro­duce he­mo­glo­bin, in­ves­ti­ga­tors work­ing for blue­bird bio $BLUE have pro­duced some com­pelling da­ta to demon­strate that their ther­a­py can elim­i­nate or re­duce the need for blood trans­fu­sions.

But they don’t have a cure — yet.

Pub­lish­ing in the New Eng­land Jour­nal of Med­i­cine, the re­searchers re­port that they test­ed the treat­ment in 22 pa­tients. In the 9 pa­tients with the most se­vere form of the dis­ease, they re­port they were able to dra­mat­i­cal­ly re­duce the need for blood trans­fu­sions by 73% and elim­i­nate it for now in 3. Six of those pa­tients, though, have need­ed to con­tin­ue trans­fu­sions. And 12 of 13 pa­tients with a less se­vere form of the dis­ease cur­rent­ly no longer re­quire blood trans­fu­sions af­ter a sin­gle treat­ment — with a me­di­an of 26 months trans­fu­sion-free.

The in­ter­im da­ta great­ly ex­pands on the pa­tient ex­pe­ri­ences they can now bank on to demon­strate the ef­fi­ca­cy of the at­tempt at a once-and-done ther­a­py which af­fects hun­dreds of thou­sands of pa­tients. And the in­ves­ti­ga­tors have not aban­doned an at­tempt to find a com­plete cure for all.

“There is room for im­prove­ment, as we’d like to see the elim­i­na­tion of de­pen­den­cy on trans­fu­sion even for pa­tients with the most se­vere form of the dis­ease,” Har­vard Med­ical’s Philippe Leboulch told their in-house pub. “But there is al­so hope with pro­to­col mod­i­fi­ca­tions we have in­tro­duced in our Phase III tri­als.”

Blue­bird — run by CEO Nick Leschly — was forced to go back and change the man­u­fac­tur­ing process on Lenti­Glo­bin af­ter some un­even re­spons­es ear­ly on. Last sum­mer, the com­pa­ny came up with some en­cour­ag­ing da­ta on the first three pa­tients.

The gene ther­a­py is made by ex­tract­ing blood stem cells from pa­tients and in­sert­ing a func­tion­al be­ta-glo­bin gene in­to them, trans­plant­i­ng them af­ter a round of chemo to clear their bone mar­row.

Jerome Groop­man in The New York­er writes:

The chal­lenge now is find­ing ways to im­ple­ment a com­plex, po­ten­tial­ly life-sav­ing treat­ment in parts of the world where med­ical care is lim­it­ed. Es­tab­lished fa­cil­i­ties for au­tol­o­gous mar­row trans­plan­ta­tion al­ready ex­ist in many de­vel­oped na­tions, as do lab­o­ra­to­ries that can in­tro­duce a healthy glo­bin gene in­to stem cells. But, in some parts of the world where be­ta tha­lassemia is most com­mon, these fa­cil­i­ties do not yet ex­ist.

Con­trary to what the en­thu­si­asts may be pre­sent­ing to­day, there’s clear­ly room for im­prove­ment. And blue­bird is clear­ly not alone in the field try­ing to pro­duce a cure. CRISPR Ther­a­peu­tics, for ex­am­ple, has been us­ing its gene edit­ing tech to see if it can find a last­ing cure for the dis­ease. And those oth­er pro­grams, in­clud­ing ef­forts at Bel­licum, will like­ly con­tin­ue to see if they can leapfrog blue­bird with some­thing bet­ter.


blue­bird bio CEO Nick Leschly Get­ty

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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Oc­u­lar Ther­a­peu­tix ham­mered by a PhII fail­ure in dry eye dis­ease — shares tank

Ocular Therapeutix $OCUL has had its ups and downs in the 7 years since it went public. Friday was one of those down days.

The Bedford, MA-based biotech reported that its lead experimental eye drug, OTX-CSI (cyclosporine intracanalicular insert), failed a Phase II trial for dry eye disease. And the stock experienced one of its periodic meltdowns, dropping more than 30% ahead of the bell.

The therapy flat failed the primary endpoint: increased tear production at 12 weeks as measured by the Schirmer’s Test compared to the vehicle control group. And while investigators called out an improvement from baseline in “signs of dry eye disease as measured by total corneal fluorescein staining (CFS) and symptoms of dry eye disease as measured by the visual analogue scale (VAS) eye dryness in subjects treated with the OTX-CSI insert,” it wasn’t statistically significant.

Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.