Following bluebird's FDA Win, 4 Companies Aim High with New Gene Therapies

Gene therapy research

Following the U.S. Food and Drug Administration’s Cell, Tissue and Gene Therapies Advisory Committee recommending two of bluebird bio’s lentiviral vector (LVV) gene therapies on Friday,  several companies developing their own gene therapies may be breathing a little easier.  

The first of bluebird's gene therapies is betibeglogene autotemcel (beti-cel) for beta-thalassemia. The second, elivaldogene autotemcel (eli-cel), is intended to treat cerebral adrenoleukodystrophy (CALD) in children ineligible for stem cell transplant from a matching donor.

If the agency approves the therapies, they will join only a few gene therapies on currently on the market, including Celgene/Bristol Myers Squibb’s Abecma (idecabtagene vicleucel), Janssen/Johnson & Johnson’s Carvykti (ciltacabtagene autoleucel) and Spark Therapeutics’ Luxturna (voretigene neparvovec).

Typically, these therapies are extraordinarily expensive. Both of bluebird’s had been approved in Europe, but with a price of $2.6 million for treatment, the company ran into reimbursement issues that eventually forced it to pull them off the market and focus on the U.S. The rationale for the high prices is two-fold: they are extremely complex, cutting-edge therapies, and they are usually designed to cure a disease and replace life-long treatments, which may be very cost-effective.

Here's a look at some of the gene therapies that may be following in bluebird’s flight path.


Cambridge, MA-based Avrobio includes several gene therapies. On May 17, the company reported positive data from its Phase I/II trial of AVR-RD-04, an investigational gene therapy for cystinosis. The trial was in adults diagnosed with the infantile form of the disease who had previously been treated with the current standard of care cysteamine.

The therapy genetically modifies the patients’ hematopoietic stem cells to express a functional form of cystinosin. Preliminary data shows that after receiving the therapy, functional cystinosin was produced throughout the body. No adverse events were reported.

A day later, the company announced preclinical data in a mouse model of its AVR-RD-03 gene therapy for infantile-onset Pompe disease. The therapy significantly decreased the toxic accumulation of glycogen in the mouse model.

Orchard Therapeutics

Orchard Therapeutics, based in Boston and London, has a gene therapy, Libmeldy, approved in Europe. The gene therapy is indicated for metachromatic leukodystrophy (MLD). It plans a pre-Biologics License Application (BLA) meeting with the FDA for the therapy under the label OTL-200 in late 2022 or early 2023.

This drug is also a good example of the price range — in May, the company finalized a reimbursement deal with Germany for a negotiated price of €2.475 million ($2.59 million U.S.). The company also has another therapy, Strimvelis, approved in Europe for immunodeficiency due to adenosine deaminase deficiency. And yet another is in the clinic, OTL-103, an ex vivo autologous gene therapy for Wiskott Aldrich syndrome.


Based in Lexington, MA and Amsterdam, uniQure announced on May 24 that the FDA had accepted the BLA submitted by CSL Behring for etranacogene dezaparvovec, a gene therapy for adults with hemophilia B. It is under priority review. The BLA is built on data from the pivotal Phase III HOPE-B trial. In studies, it significantly decreased the rate of annual bleeds after a single one-time infusion.

“Etranacogene dezaparvovec has the potential to be the first gene therapy approved in hemophilia B and the acceptance of the BLA marks an important milestone in uniQure’s mission of delivering the promise of gene therapy to people living with rare diseases,” Matt Kapusta, uniQure’s CEO, said in a statement. “UniQure has been a leader in gene therapy for nearly 25 years and, if approved, etranacogene dezaparvovec would represent our second gene therapy to complete its journey to patients.”


RegenxBio, based in Rockville, MD, has partnered with AbbVie to develop RGX-314, which is being assessed in a Phase III trial for wet AMD (subretinal) and Phase I/II for wet AMD (suprachoroidal) and diabetic retinopathy. It also had therapies in Phase I/II for Duchenne muscular dystrophy and Hurler syndrome.

On June 9, the company opened its new Manufacturing Innovation Center gene therapy facility in Rockville. It will allow the company to increase the manufacturing of NAV Technology-based AAV vectors at scales up to 2,000 liters. It invested more than $100 million into the buildout of its Rockville headquarters, including more than $65 million in the Manufacturing Innovation Center. It also has hired 200 people over the last two years.

The NAV Technology Platform consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8, AAV9 and AAVrh10.

“In-house manufacturing is a key differentiator for RegenxBio as a leader in gene therapy,” Curran Simpson, the company’s chief operations and technology officer, said in a statement. “Quality manufacturing is crucial to all stages of AAV gene therapy development, and we’re extremely proud of this cutting-edge facility and the experienced team we have to lead these efforts. Bringing our manufacturing in-house allows us to control the process from beginning to end and provides flexibility to support a wide range of clinical and commercial needs.”

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