Putting patients first in the translational research pipeline

During a follow-up visit, pediatric hematologist/oncologist Sung-Yun Pai, MD, hugs a patient who received gene therapy for X-linked severe combined immunodeficiency.
During a follow-up visit at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, pediatric hematologist/oncologist Sung-Yun Pai, MD, hugs a patient who received gene therapy for X-linked severe combined immunodeficiency.

This is part II of a two-part blog series recapping the 2018 BIO International Convention. Read part I: Forecasting the convergence of artificial intelligence and precision medicine.

The hope to improve people’s lives is what drives many members of industry and academia to bring new products and therapies to market. At the BIO International Convention last week in Boston, there was lots of discussion about how translational science intersects with patients’ needs and why the best therapeutic developmental pipelines are consistently putting patients first.

As a case in point, Mustafa Sahin, MD, PhD, of Boston Children’s discussed his work to improve testing and translation of new therapies for autism spectrum disorder (ASD). As a member of PACT (Preclinical Autism Consortium for Therapeutics) and director of Boston Children’s Translational Neuroscience Program, Sahin aims to bridge the gap between drug discovery and clinical translation.

“Our mission is to de-risk entry of new therapies in the ASD drug discovery and development space,” said Sahin, who is also a professor of neurology at Harvard Medical School.

One big challenge, says Sahin, is knowing how well — or how poorly — autism therapies are actually affecting people with ASD. Externally, ASD is recognized by its core symptoms of repetitive behaviors and social deficits.

To get a deeper look at therapeutic effects, Sahin has studied several mouse models bearing the same genetic mutations that affect human patients with autism. He is using round-the-clock electroencephalography to measure brain rhythms and other “invisible” metrics that can be used to analyze a drug compound’s true efficacy.

Experimental therapies for childhood cancers

In another panel about clinical trial considerations for pediatric oncology and beyond, Rani George MD, PhD, an attending pediatric oncologist at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, discussed the translation challenges she sees.

“To begin with, druggable genetic mutations are really very rare in pediatric tumors,” said George, who is also an associate professor of pediatrics at HMS. “As a physician-scientist, I see a great deal of very good cancer research and preclinical data, but then academia alone isn’t primed to encourage further testing and validation.”

Despite these challenges, she sees a striking willingness from patients’ families to try emerging therapies when industry partnerships enable them to reach the bedside.

“In my experience, 98 percent of parents want to try every option — including the newest, experimental therapies — to treat their child’s cancer,” George said.

Gene therapy and its promise for patients with genetic disease

The gene therapy development boom, a rapidly expanding biotechnology space at the intersection of experimental therapies and the latest advances in genetic engineering, is patient-focused from the start.

Pediatric hematologist/oncologist David Williams, MD, who is chief scientific officer at Boston Children’s, which sponsored BIO’s Orphan and Rare Diseases educational track, says he sees no lack of genetic targets to pursue for development of new therapies to treat pediatric diseases, including cancers.

“We see the rarest of the rare genetic diseases,” Williams remarked during a panel conversation about how gene therapies are becoming a reality for patients across the U.S.

Last year, Williams and colleagues at Boston Children’s and Massachusetts General Hospital announced the results of a clinical trial to evaluate the use of a new gene therapy to treat cerebral adrenoleukodystrophy, or ALD, a devastating neurodegenerative disease that typically strikes young boys. ALD, caused by a defective gene on the X chromosome that ultimately damages the protective myelin sheaths of the brain’s neurons, has typically claimed boys’ lives within 10 years of diagnosis.

David Williams, MD, the principal investigator of the clinical trial, discusses gene therapy and its impact on children with adrenoleukodystrophy

For the first time, however, there seems to be a way to stop ALD in its tracks. Following the clinical trial, sponsored by Bluebird Bio, the disease’s progression has been halted in 15 out of 17 boys who were treated with the gene therapy. If gene therapy can treat ALD, how many other genetic diseases can it work for? For many patients and families affected by genetic disease, hope has blossomed from the trial’s results.

What “patients first” means when it comes to gene therapy

With so many gene therapies similar to the ALD therapy now attracting industry interest, Williams says that putting the patient first helps prioritize which gene therapies to pursue.

“Our priority is always the medical need of our patients,” said Williams, who is also president of Dana-Farber/Boston Children’s and the Leland Fikes Professor of Pediatrics at HMS.

From an industry perspective, Jeffrey Walsh of Bluebird Bio says that the regulatory environment is much more receptive to gene therapies than it was five to ten years ago.

“The clinical data on gene therapies is creating excitement and bringing larger companies and more human and financial capital into the field,” Walsh said.

Today, the draw of gene therapy brings families with an eligible patient across great distances to the far and few hospitals who have the special expertise to deliver them. In the long run, Williams hopes that gene therapy will become more standardized so that it can be administered at more medical centers around the country.

He also hopes that insurance models will adapt in pace with accelerating clinical innovation, citing the stark contrast between the cost of a one-time gene therapy and the cost of life-long care for patients with the most serious genetic diseases.

“For the first time, we are really having to think about the value of healthcare and what it means in the setting of emerging one-time treatments for otherwise incurable genetic diseases,” Williams said.

Learn more about gene therapy at Boston Children’s.