The Future of Oral Oncolytics


Peter Salgo, MD: I don’t want that cancer benefit, I need it. You know that’s an issue too. Let’s go back. We started this whole discussion about oral oncolytics, and we have branched every which way, from Sunday, maybe from Monday too. But I want to come back to the future of these drugs. Are they the future really of therapy for multiple myeloma? Is this where we’re going?

Noa Biran, MD: Absolutely.

Peter Salgo, MD: Is this where we’re going?

Noa Biran, MD: Absolutely. I think there’s no doubt that these drugs are not going away. You know the IMiDs [immodulatory drugs] are still the backbone, and now there are new IMiDs in development that are kind of the new more potent version of the drug. There are other oral agents in development, more potent proteasome inhibitors. So patients like having oral options and physicians like having it, and they work. And at the end of the day, it’s a uniformly fatal disease for which we rely on novel therapies.

Peter Salgo, MD: Except that, you know, I’m almost tempted to say that’s not really a good definition, because life is an ultimately fatal disease. And if what you’re telling me is you’ve got 20 years, for somebody with an average age you told me already in the mid-60s or 70s. Now we’re talking mid-80s, right?

Noa Biran, MD: Right.

Peter Salgo, MD: So 20 years. So it’s a chronic disease.

Noa Biran, MD: So for most patients, yes. There’s a subset of patients, and it’s not a small subset, 25%, have high-risk genetics and are high risk or functionally high risk. Their lifespan is still about 2 years or less.

Peter Salgo, MD: OK. Now, is there an availability issue in the pipeline right now for these oral agents for patients who need them?

Cheryl Allen, BPharm, MBA: Availability, I would say.

Peter Salgo, MD: In other words, out of the factory, do we have enough drug?

Cheryl Allen, BPharm, MBA: We have enough drug. I think where we’re challenged is enough patients in clinical trials. So as Dr. Biran said, you know where we’re going is very targeted therapies that are even better. You know, it’s the next generation in these types of targeted therapies, yet we don’t have the patients in the clinical trials. We’re working a rare disease here.

Peter Salgo, MD: And she says, sometimes if you can’t get the clinical trials, the patients who really need the drugs most can’t get them because they won’t get approval. So we need more oral oncolytics. We need more patients on them, and more studies.

Cheryl Allen, BPharm, MBA: And to that point, let’s go back to the example. You know the health plan is pushing back on a clinical trial that involved 100 patients, or 70 patients, right? So it’s going to continue to be challenging for patients as we work with this disease. When patients relapse, they go on another regimen, and they continue on the pathway.

Peter Salgo, MD: OK, let’s use a crystal ball. It’s now 10, 15 years in the future. Are IV [intravenous] oncolytics gone? Is it all oral oncolytics now? Is there a place for the IV drugs?

Noa Biran, MD: The treatment landscape is changing so quickly, you know a year ago we would have told you that CAR [chimeric antigen receptor] T cells were the be-all and end-all in that there would not be a need for a transplant or IV, oncolytics or oral oncolytics, because CAR T cells were going to cure everybody. As it turns out, almost everybody has relapsed. The way we are administering CAR T cells, yes, they give a durable remission for patients who have very few options, but at the end of the day they’re relapsing, and we do go back to these old drugs. And you know, they’re not old, but we still even need thalidomide, and we still go back to melphalan, which is 1 of the oldest and most effective drugs.

Peter Salgo, MD: Whoa, you’re going back to my medicines, melphalan.

Noa Biran, MD: That’s right. We use it all the time.

Peter Salgo, MD: I think we treated pterodactyls with that at 1 time.

Noa Biran, MD: So it’s a question of and in a patient with myeloma, not instead of.

Cheryl Allen, BPharm, MBA: Though within the CAR T therapy, I think, ultimately, we’ll get more of a sustained response with some of the newer technologies that are going on right now with bluebird bio, inc, like bb21217, are looking hopefully positive for this patient population. So I’m still very hopeful that the pipeline will deliver.

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