bluebird bio Receives Positive CHMP Opinion for SKYSONA™ (elivaldogene autotemcel, Lenti-D™) Gene Therapy for Patients Less Than 18 Years of Age with Early Cerebral Adrenoleukodystrophy (CALD)

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SKYSONA is the primary and solely gene remedy advisable for approval for sufferers with CALD, a progressive, neurodegenerative illness

As of the info cutoff date, 90% of sufferers (27/30) handled with SKYSONA within the pivotal ALD-102 scientific examine met the first endpoint of main practical incapacity (MFD)-free survival at two years of follow-up

Information from the long-term follow-up examine (LTF-304) counsel that SKYSONA continues to indicate a sturdy impact on MFD-free survival, with the longest follow-up of practically seven years (82.7 months)

Amongst 51 sufferers handled with SKYSONA throughout scientific research to this point, there have been no reviews of graft-versus-host illness (GVHD), graft failure or rejection, or transplant-related mortality (TRM)

CAMBRIDGE, Mass. — bluebird bio, Inc. (Nasdaq: BLUE) immediately introduced that the Committee for Medicinal Merchandise for Human Use (CHMP) of the European Medicines Company (EMA) adopted a constructive opinion recommending advertising and marketing authorization for SKYSONA™(elivaldogene autotemcel, Lenti-D™), a one-time gene remedy for the remedy of early cerebral adrenoleukodystrophy (CALD) in sufferers lower than 18 years of age with an ABCD1 genetic mutation, and for whom a human leukocyte antigen (HLA)-matched sibling hematopoietic stem cell (HSC) donor isn’t accessible. If accredited by the European Fee (EC), SKYSONA would be the first one-time gene remedy accredited to deal with CALD, a uncommon neurodegenerative illness that happens in childhood and may result in progressive, irreversible lack of neurological perform and demise.

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The CHMP’s constructive opinion will now be reviewed by the EC, which has the authority to grant advertising and marketing authorization for SKYSONA within the European Union (EU). A CHMP constructive opinion is likely one of the last steps earlier than the EC decides whether or not to authorize a brand new medication. A last choice by the EC for SKYSONA is anticipated in mid-2021. SKYSONA isn’t accredited for any indication in any geography.

“The purpose of remedy with SKYSONA is to stabilize illness development in youngsters with CALD for whom a matched sibling donor isn’t accessible, with a view to forestall additional neurological decline and enhance survival for these younger sufferers,” stated Richard Colvin, M.D., Ph.D., interim chief medical officer, bluebird bio. “This constructive opinion from the CHMP marks the primary regulatory approval advice for any gene remedy for CALD, bringing us nearer to a one-time, sturdy remedy possibility that stabilizes neurological illness whereas decreasing the chance of the intense immune issues related to allogeneic stem cell transplantation (allo-HSCT), which is the one therapeutic possibility for kids with this devastating illness. Along with the ALD group and scientific investigators, we’re all optimistic that new hope may quickly be offered to sufferers affected by this insufferable situation.”

Adrenoleukodystrophy (ALD) is a uncommon, X-linked metabolic dysfunction that primarily impacts males; worldwide, an estimated one in 21,000 male newborns are recognized with ALD. The dysfunction is brought on by mutations within the ABCD1 gene that have an effect on the manufacturing of adrenoleukodystrophy protein (ALDP) and subsequently trigger poisonous accumulation of very long-chain fatty acids (VLCFAs), primarily within the adrenal gland and white matter of the mind and spinal twine. Roughly 40% of boys with ALD will develop CALD, probably the most extreme type of ALD. CALD is a progressive and irreversible neurodegenerative illness that entails the breakdown of myelin, the protecting sheath of the nerve cells within the mind accountable for pondering and muscle management. The onset of signs of CALD sometimes happens in childhood (median age 7).

“The speedy and progressive decline of cognitive and bodily capabilities for a kid residing with CALD is agonizing for folks, households and healthcare suppliers to witness. With CALD, every day actually counts, as practically half of the sufferers who don’t obtain remedy will die inside 5 years of symptom onset,”¹ stated Jean-Hugues Dalle, M.D., Ph.D., HSCT and Gene Remedy program director, Robert Debré Hospital, GH Nord Université de Paris, France. “As a clinician, I stand with my fellow investigators in our continued dedication to enhance outcomes for kids recognized with CALD, together with the development of an accredited remedy possibility like SKYSONA.”

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“Households affected by CALD face a essential prognosis, as signs that typically develop in childhood lead to a progressive lack of autonomy and speedy neurological decline. There’s an pressing want for remedy choices,” stated Man Alba, President of ELA Worldwide and founding father of the ELA affiliation. “The ELA affiliation has proven the way in which by investing massively in CALD analysis since 1992. We help all initiatives that, like gene remedy, may change the lives of sufferers. This milestone is a vital step ahead in choices for the care of sufferers with CALD.”

SKYSONA is a one-time investigational gene remedy that makes use of ex vivo transduction with the Lenti-D lentiviral vector (LVV) so as to add practical copies of the ABCD1 gene right into a affected person’s personal hematopoietic (blood) stem cells (HSCs). The addition of the practical ABCD1 gene permits sufferers to provide the ALD protein, which is believed to facilitate the breakdown of VLCFAs. The purpose of remedy with SKYSONA is to stabilize the development of CALD and, consequently, protect as a lot neurological perform as potential, together with the preservation of motor perform and communication skill. Importantly, with SKYSONA, there isn’t any want for donor HSCs from one other individual.

In October 2020, the EMA accepted bluebird bio’s Advertising and marketing Authorisation Utility (MAA) for its investigational SKYSONA gene remedy for the remedy of sufferers with CALD. SKYSONA was accepted into the EMA’s Precedence Medicines scheme (PRIME) in July 2018 and was beforehand granted Orphan Medicinal Product standing.

Information Supporting Scientific Profile of SKYSONA

The constructive CHMP opinion is supported by efficacy and security knowledge from the Section 2/3 Starbeam examine (ALD-102). All sufferers who accomplished ALD-102, plus those that will full a second Section 3 examine (ALD-104), will likely be requested to take part in a long-term follow-up examine (LTF-304).

The first efficacy endpoint of the pivotal ALD-102 examine was the proportion of sufferers who didn’t have any of the six MFDs, had been alive, didn’t obtain a second allo-HSCT or rescue cell administration and had not withdrawn or been misplaced to follow-up at Month 24. Up to now, 32 sufferers have been handled with SKYSONA in ALD-102, and 30/32 sufferers had been evaluable for follow-up at Month 24. As of the final knowledge cutoff date, 90% (27/30) of the sufferers met the Month 24 MFD-free survival endpoint. As well as, as beforehand reported, two sufferers withdrew from the examine at investigator discretion, and one skilled speedy illness development early on within the examine, leading to MFDs and subsequent demise.

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In ALD-102, 26/28 evaluable sufferers maintained a neurologic perform rating (NFS) lower than or equal to 1 by Month 24, and 24 of these sufferers had no change of their NFS, which confirmed upkeep of neurological perform within the majority of sufferers. All sufferers who accomplished ALD-102 enrolled for long-term follow-up within the LTF-304 examine. The median period of follow-up was 38.59 months (min.: 13.4; max.: 82.7).

The remedy routine, comprising mobilization/apheresis, conditioning and SKYSONA infusion, had a security/tolerability profile primarily reflective of the recognized results of mobilization/apheresis and conditioning.

Adversarial reactions attributed to SKYSONA noticed in scientific trials embrace cystitis viral, pancytopenia and vomiting.

There have been no reviews of GVHD, graft failure or rejection, TRM or replication competent lentivirus within the 51 sufferers handled with SKYSONA in scientific research (ALD-102/LTF-304 and ALD-104). Moreover, there have been no reviews of lentiviral vector-mediated insertional mutagenesis leading to oncogenesis, together with myelodysplasia, leukemia or lymphoma, related to SKYSONA. Nonetheless, there’s a theoretical danger of malignancy after remedy with SKYSONA. Clonal growth leading to clonal predominance with out scientific proof of malignancy has been detected in some sufferers handled with SKYSONA.

SKYSONA continues to be evaluated within the Section 3 ALD-104 examine and the long-term follow-up examine LTF-304. If accredited by the EC, sufferers handled with SKYSONA in Europe will likely be anticipated to enroll within the REG-502 Stargazer registry.

About SKYSONA (elivaldogene autotemcel, previously Lenti-D™ gene remedy)

The U.S. Meals and Drug Administration (FDA) granted SKYSONA Orphan Drug standing, Uncommon Pediatric Illness designation and Breakthrough Remedy designation for the remedy of CALD. bluebird bio is at present on monitor to submit the Biologics License Utility (BLA) within the U.S. by mid-2021.

SKYSONA isn’t accredited for any indication in any geography.

The Section 3 ALD-104 examine, designed to evaluate the efficacy and security of SKYSONA after myeloablative conditioning utilizing busulfan and fludarabine in sufferers with CALD, is approaching enrollment completion; enrollment in Europe is anticipated to be closed on the finish of Could.

The Section 2/3 Starbeam examine (ALD-102) is full. For extra details about our research, go to: www.bluebirdbio.com/our-science/clinical-trialsor clinicaltrials.gov.

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Moreover, bluebird bio is conducting a long-term security and efficacy follow-up examine (LTF-304) for sufferers who’ve been handled with SKYSONA for CALD and accomplished two years of follow-up in bluebird bio-sponsored research. If accredited by the EC, sufferers handled with SKYSONA in Europe will likely be anticipated to enroll within the REG-502 Stargazer registry.

About CALD Early Analysis

Early prognosis of CALD is important, as remedy have to be administered earlier than the illness progresses too far, as the result of remedy varies with the scientific stage of the illness. New child screening is a essential enabler of early prognosis for ALD and offers entry to a window of alternative for the well timed graduation of accessible therapies. As soon as a affected person has been recognized with ALD, common MRI scans are essential to detect white matter modifications indicative of development to CALD as at present, there isn’t any strategy to predict who with ALD will develop CALD. Within the absence of new child screening for ALD, early detection of ALD signs is essential to permit for well timed remedy.

Sadly, in most EU nations, there isn’t any new child screening for ALD, and due to this fact it’s tough to detect sufferers prone to growing CALD. Up to now, the Netherlands is the one nation in Europe that has accredited the addition of ALD to their new child screening panel.

Within the U.S., new child screening for ALD was added to the Advisable Common Screening Panel in February 2016 and is at present energetic in 19 states and the District of Columbia, accounting for >60% of U.S. newborns.

About bluebird bio, Inc.

bluebird bio is pioneering gene remedy with objective. From our Cambridge, Mass., headquarters, we’re growing gene and cell therapies for extreme genetic illnesses and most cancers, with the purpose that folks going through doubtlessly deadly situations with restricted remedy choices can reside their lives totally. Past our labs, we’re working to positively disrupt the healthcare system to create entry, transparency and training in order that gene remedy can change into accessible to all those that can profit.

bluebird bio is a human firm powered by human tales. We’re placing our care and experience to work throughout a spectrum of problems: cerebral adrenoleukodystrophy, sickle cell illness, β-thalassemia and a number of myeloma, utilizing gene and cell remedy applied sciences together with gene addition, and (megaTAL-enabled) gene enhancing.

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bluebird bio has further nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For extra info, go to bluebirdbio.com.

Comply with bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

SKYSONA, eli-cel, Lenti-D and bluebird bio are emblems of bluebird bio, Inc.

Ahead-Wanting Statements

This launch comprises “forward-looking statements” inside the which means of the Non-public Securities Litigation Reform Act of 1995, together with statements concerning the corporate’s expectations and plans for regulatory submissions and approvals for eli-cel within the European Union and america. Any forward-looking statements are based mostly on administration’s present expectations of future occasions and are topic to plenty of dangers and uncertainties that might trigger precise outcomes to vary materially and adversely from these set forth in or implied by such forward-looking statements. These dangers and uncertainties embrace, however aren’t restricted to: the chance that the EC doesn’t grant advertising and marketing authorization to eli-cel on the timeline that we count on, or in any respect, the dangers that the efficacy and security outcomes for eli-cel from the Starbeam Research and ALD-104 seen to this point won’t proceed or persist; the dangers concerning future potential regulatory approvals of eli-cel, together with the chance that the Starbeam Research will likely be inadequate to help regulatory submissions or advertising and marketing approval within the U.S., or that the FDA might require further knowledge or info past our present expectations, the chance that our submissions for regulatory approval within the U.S. won’t be submitted or accepted for submitting by the FDA on the timeframe we count on or in any respect; and the chance that eli-cel is related to insertional oncogenesis or different security occasions that influence the risk-benefit profile of the remedy. For a dialogue of different dangers and uncertainties, and different vital components, any of which may trigger our precise outcomes to vary from these contained within the forward-looking statements, see the part entitled “Danger Components” in our most up-to-date Kind 10-Q, in addition to discussions of potential dangers, uncertainties, and different vital components in our subsequent filings with the Securities and Alternate Fee. All info on this press launch is as of the date of the discharge, and bluebird bio undertakes no responsibility to replace this info except required by legislation.

¹ Reported Kaplan-Meier estimated five-year survival charges amongst untreated sufferers are 55% (from the time of CALD prognosis) and 59% (from the time of onset of first scientific signs).

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Contacts

Media:
Victoria von Rinteln, 617-914-8774
vvonrinteln@bluebirdbio.com

Catherine Falcetti, 617-583-3411
cfalcetti@bluebirdbio.com

Buyers:
Elizabeth Pingpank, 617-914-8736
epingpank@bluebirdbio.com