Stefano Rivella recently returned from Malaysia where he attended a conference on thalassemia and hemoglobinopathies. While there, he was concerned that the questions asked focused more on the availability of innovations rather than treating patients with these conditions – simply because the price is too high for people who live in countries like Malaysia.

Rivella, the leader of the RNA Gene Therapeutics Group at The Penn Institute for RNA Innovation, as well as a Professor of Pediatrics at the Children’s Hospital of Philadelphia, spoke to NPF Covering Rare Diseases Fellows about his research on hematological and metabolic disorders—and about his quest to ensure that these innovations will be available to all who need them.

What is gene addition?

Rivella told fellows that there are three ways gene therapy can treat a patient with sickle cell anemia or beta-thalassemia. The first is by adding back a healthy copy of the beta-globin gene to the cells of the patient that has the mutation in the beta-globin gene. The second is reactivating the gamma-globin gene, and the third is correcting the mutation in the beta-globin gene.

“You need to consider two components when you think about gene therapy. The first is you want to transfer the hardware, which is the gene you want to express in the cells of the patient, and the second is that you need to transfer enough of the software so that the gene would be expressing the proper way.”

“In other words, we take the envelope, we discard the letter inside, and we replace the letter with a new kind of information so that was able to deliver a functional copy of the beta-globin gene into the cells of the patient.”

CHOP is trying to Lower the Cost of Vector treatment.

While studying in New York, Rivella helped design a lentiviral vector, which he was able to use to increase the hemoglobin levels in animals affected by thalassemia major.

A similar lentiviral vector technology was then used for the treatment of patients with thalassemia, but the price tag for each treatment was a high cost – $2.8 million, he said.

Since 2015, Rivella has been working at CHOP in Philadelphia, where he established the CurRED Center. They are working to make the vector themselves, hopefully at a cheaper cost.

“So far, all the trial has been sponsored by CHOP. I’m not saying it’s going to be cheap. I’m not going to say that this is the way to treat all the patients, unfortunately, because we can talk in detail about how much it costs to make a vector, how much it costs to treat the patient with American insurance, et cetera. But at least we will be able to treat a few patients in our center with the novel vector we made with a definitely lower price than the company can present now to the patients.”

In Vivo Therapy has the potential to advance the field of gene therapy, he said.

A major limitation in gene therapy has been the necessity of using ex vivo therapy – the process of manipulating the cells outside of the body and then putting them back in.

“This is really a challenge because increase not only the manipulation, the viability, decrease the viability of the cells you’re using for the manipulation or for the infusion, et cetera, but the myeloablation also comes with the loss of fertility.”

In Vivo gene therapy can eliminate or simplify the myeloablative regimens, he said. “Or, if we can directly do in vivo gene editing, there is no requirement for myeloablation so the patient will not need to go to the hospital. They can get an injection by a nurse, and this can be done in any country without a sophisticated, specialized clinical center to do the gene therapy.”

Confronting the global health care crisis

Although not an economist, Rivella believes that countries should prioritize investing in scientific education and policies that will ultimately allow them to develop these innovative treatments themselves.

“My way to subsidize this would be allowing countries to make their own medication, to establish facilities in those countries that will awfully make these drugs a lower price and subsidize these, so then if we don’t subsidize directly the drug to each patient, we may be able to create drugs that are much cheaper to start with in those countries.”

Access the full transcript here.