Gene Therapy: Can it have therapeutic applications beyond rare diseases?

Three decades have passed since Ashanti DeSilva, the first patient to receive gene therapy in the US, was successfully treated for adenosine deaminase (ADA) deficiency, a genetic condition that causes a life-threatening disorder called severe combined immunodeficiency (SCID).

Over the past decade, cell and gene therapies have made incredible clinical progress- begging the question: How far can gene therapies go?

Research across public and private sectors are working eagerly to improve the design of
the delivery vectors to deliver safer and more durable gene therapy treatments.
On the other hand, more effort is needed to improve the accessibility of cell
and gene therapies so that they can potentially have wider applicability beyond
rare diseases.

The gene therapy era is here

Cell and gene therapy has made a significant impact in the field of Oncology. CAR-T therapies have revolutionized late-stage cancer treatment by delivering hope to the most
severe patients suffering from blood cancers. Yescarta, a CAR-T therapy approved in 2017 for adult patients with relapsed or refractory large B-cell lymphoma after they’ve failed two or more lines of systemic therapy, has delivered a 44% chance of survival at 4 years. This means patients no longer need to give up hope when their conventional treatment options like chemotherapy or a bone marrow transplant have failed. The question is why wait? Can early treatment with CAR-T spare the need for transplants and chemotherapy
and deliver better outcomes for patients?

It is possible; however, the clinical potential of CAR-Ts is currently limited by several factors such as access to treatment, the time needed to engineer the cells, and the potential risk of serious side effects. However, with innovations on the horizon, such as “off-the-shelf” CAR-T cells, as well as the potential for expansion into the treatment of solid tumours, CAR-Ts have the potential to become a staple among conventional treatments in Oncology.

Haemophilia is another disease on the cusp of being transformed by the availability of gene
therapies, as two late-stage products await to gain regulatory approval following the regulatory setbacks they were hit with last year.

The FDA rejected Biomarin’s haemophilia A therapy, Roctavian, amid durability concerns. The agency requested an additional 2 years of data from the phase III study to offer substantial evidence of a durable effect. UniQure’s haemophilia B gene therapy was hit with a regulatory hold after a recipient of the treatment developed hepatocellular carcinoma (HCC) in the HOPE-B pivotal trial. Earlier this year, the company announced that the FDA has lifted the hold, and later announced positive 52-week data from its pivotal trial, placing the treatment back on track and inching one step closer to regulatory approval.

What are the prospects for cell and gene therapies beyond rare diseases?

As innovators improve upon the technology, manufacturing capabilities, and accessibility of cell and gene therapies, the reality of a broader application beyond rare diseases becomes more tangible. One company that aims to tackle the accessibility issue is Ensoma, a Boston-based biotech established in 2019. Earlier this year, the company landed a $70M deal with Takeda as they join in a strategic collaboration to develop “off-the-shelf” genomic medicines. “With its vectors, Ensoma is developing in vivo genomic medicines that don’t need conditioning treatments, so people can receive them in an outpatient setting.”

Kriya Therapeutics is another company with a big vision, which unlike most companies developing treatments in the gene therapy space, is looking to develop a lower cost gene therapy for more common diseases like diabetes (type 1 and type 2), a condition affecting over 34 million Americans8. The California based biotech raised $100M this year, over the $80 million it raised in 2020 to support this effort.

The success of gene therapies in rare diseases has greatly expanded the possibilities of what it means to treat diseases. Over the next two to three decades gene therapy will continue to raise therapeutic expectations for millions of patients suffering from more common conditions such as diabetes, cardiovascular disease, HIV, and neurologic conditions such as Parkinson's disease, and Alzheimer's disease.

Notes: In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people in the US.

References:

Gene Therapy: Can it have therapeutic applications beyond rare diseases?

Subscribe to our newsletter for more insights.

Further reading

The light we don't shine

Hark! The unmistakable sound of Purpose and why your asset needs it!!