Entrance to the Bethesda, Maryland, headquarters of the National Center for Advancing Translational Sciences (NCATS), a division of the National Institutes of Health. (Photo by Larry Luxner)

BETHESDA, Maryland—Hoping to speed up efforts to treat a variety of extremely rare genetic diseases, the Foundation for the National Institutes of Health (FNIH)—along with 35 public, private, and nonprofit partners—has launched the Bespoke Gene Therapy Consortium (BGTC).

This ambitious venture involves the NIH’s National Center for Advancing Translational Sciences (NCATS) and is led by Philip J. Brooks, PhD, acting director of the division of rare diseases research innovation at NCATS.

Among the consortium’s goals are:

  • Make adeno-associated virus (AAV) technology more accessible in a broader range of diseases.
  • Accelerate the potential to streamline preclinical and product testing.
  • Facilitate scientific and regulatory advances that will ultimately benefit the entire field.
  • Bring gene therapies to all individuals in need sooner.

The venture was established on October 27, 2021, and has since raised $81.4 million—$41.9 million from private sources and $39.5 million from public funds.

“The consortium is looking for better and more efficient ways to get gene therapy trials up and running, particularly for diseases that are of no commercial interest because they’re so rare,” Dr. Brooks told Rare Disease Advisor from NCATS headquarters in Bethesda, Maryland.

He noted that only about 600 of the 7000 or so known rare diseases have approved therapies—meaning that at current rates, it would take about 2000 years to find treatments for all of them.

“This just goes to illustrate the point that we really have to do something different if we want to treat, or even open clinical trials, for all these diseases,” said Dr. Brooks, who also spoke at the recent National Organization for Rare Disorders (NORD) Breakthrough Summit 2022.

“One way is to stop doing things just one disease at a time, and to develop and implement therapeutic platforms such as AAV gene therapy,” he said. “That’s what we’re trying to do with the BGTC: make it so it’s not always a complete one‑off situation where everything has to be done from scratch.”

Finding Commercial Viability 

The BGTC is the 8th—and the largest—of 10 initiatives under the Accelerating Medicines Partnership program, a public-private entity managed by the FNIH that includes the NIH and the US Food and Drug Administration (FDA) as well as other partners.

Eleven branches of NIH are part of the consortium, along with a dozen pharmaceutical companies, such as Biogen, Janssen, Pfizer, Novartis, and Ultragenyx. Besides NORD, other partnering patient advocacy groups include the Alliance for Regenerative Medicine, the American Society of Gene & Cell Therapy, and CureDuchenne.

P.J. Brooks, PhD (Photo courtesy of the National Center for Advancing Translational Sciences)

Dr. Brooks is on the BGTC steering committee along with cochairs Gregory LaRosa, PhD, senior vice president and head of scientific research at Pfizer’s Rare Disease Research Unit, and Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“Our goal is to try to help streamline the creation of important products for patients,” Dr. Marks said at an event marking the venture’s first anniversary. “We have to find a way to commercial viability if we’re going to succeed, and we have to figure out what’s going to get us there.”

Added former NIH Director Francis Collins, MD, PhD: “People with terrible genetic disorders are in dire need of solutions. The BGTC promises to transform the field of gene therapy so we can treat or even cure rare diseases for which no current therapy exists.”

The FDA defines a “rare” disease as any condition affecting fewer than 200,000 Americans. By “ultrarare,” Dr. Brooks said he’s referring to conditions that affect 1 in a million people; in the United States, that would translate into 300 or so patients.

NCATS informational poster. (Photo by Larry Luxner)

“There are certainly diseases with substantially smaller numbers of patients than that,” he said. “There’s literally no business model. Even for a disease in which you treat all the patients, it’s a one-time treatment. You’d have nobody to sell your drug to.”

On the other hand, Dr. Brooks said, “many of these diseases are worldwide. So even a disease with a fairly small number of people in the U.S. might make sense for a pharmaceutical company if there’s a lot of patients in other parts of the world.”

BGTC Will Announce Final Disease List by May

With so many rare diseases lacking therapies, one of the consortium’s biggest challenges has been trying to decide which ones to tackle. Initially, only single-gene diseases are being considered, as well as those with short patient follow-ups (generally 6-12 months), those with already existing patient registries, and those without commercial value.

“We’re finding that it’s one thing to choose the disease. It’s another to actually get all the process done and get the trials funded,” Dr. Brooks said. “Various agreements have to be signed, and that can take some time.”

To date, the BGTC has received 63 submissions, all of which have been reviewed by a team of experts in AAV biology and clinical trial design. The team has identified 14 ultrarare diseases as ready for clinical trials based on required and preferred criteria. These include MPS VI corneal disease, retinitis pigmentosa, Charcot-Marie-Tooth disease (CMT) type 4J, propionic acidemia, Barth syndrome, and fibrodysplasia ossificans progressiva (FOP).

NCATS headquarters in Bethesda, Maryland. (Photo by Larry Luxner)

Proposals for clinical trials are now being reviewed, with the list of the final 5 or 6 diseases to be announced by May 2023.

“What we’ve tentatively been thinking about is to have some different target tissues and routes of administration. We’ve got several neurologic diseases, several eye diseases, and then several diseases where you’d have to deliver AAV systemically,” he said. “We want some of each type, because we want to make this whole process streamlined in as broad a way as possible.”

The consortium will hold its first annual meeting in conjunction with the 26th annual meeting of the American Society of Gene & Cell Therapy, set for May 16-20, 2023, in Los Angeles.

“The BGTC reflects an extraordinary commitment of time and effort from consortium members,” said Joni L. Rutter, PhD, the acting director of NCATS. “The initiative’s accomplishments over the past year show the BGTC is well on its way to achieving its goals.”