Makers of novel cell/gene therapy say off-the-shelf approach only way to solve pricing woes – MedCity News

Innovative treatments have turned the tables somewhat in the battle against cancer but one stumbling block appears to be pricing. CAR-T cell therapy can cost more than $1.5 million including the $475,000 cost of the drug (in this case, Kymriah from Novartis).

We are seeing that price is becoming a barrier because if you can imagine, hundreds of thousands of people all suddenly becoming eligible for CAR-T, there isnt enough money in the healthcare system to pay for that, said Paul Wotton, CEO of Obsidian Therapeutics, based in Cambridge, Massachusetts.

In a recent interview in San Francisco, Wotton and another biopharma executive pointed to a solution to the price conundrum: an off-the-shelf approach.

To clarify, to date the approved CAR-T therapies involve cells from the patients own body that are re-engineered and placed back into the body in order to overpower and kill the cancerous growth. While revolutionary, this is not only a cumbrous process but also expensive.

Now, some companies are going the route of using donor cells to develop their own treatment regimens. These are known as allogeneic therapies.

Wugen Therapeutics is one such company that is taking an allogeneic approach to CAR-T therapy. Based in St. Louis Missouri with technology developed out of Washington University, the company targets T-cell malignancies in leukemia and lymphoma, said Ayman Kabakibi, vice president of research and development. In a recent interview, he explained that so far CAR-T therapies have focused on B-cell malignancies because it is less difficult to target B-cell malignancies with a T-cell.

The reason is that if you go back to the basics of CAR-T you are trying to put a receptor (CAR) on the normal T-cell to allow it to recognize another antigen or marker on the tumor cell and when that interaction happens, two things happen the T-cell will proliferate and make more daughter cells and thats why we call it a living drug, Kabakibi explained. And the other thing that happens is that it secretes toxins that kill the tumor cells. Well, you can do that more easily for B cells because the antigens are not shared between the two.

But at Wugen, the company is using re-engineeerd normal T-cells to target cancerous T-cells and certain adjustments need to be made so that the cells dont end up killing each other.

So what we do is that we take the T-cells and we remove the antigen that we are targeting on the cancer cell using CRISPR CAS technology, he said. We take T-cells from a normal person. We eliminate that marker and then we put another gene to make it stress the receptor that it will recognize.

Why not take T-cells from the patients own body?

One reason is that in many cases by the time patients land on CAR-T therapy, they may have already undergone several rounds of other treatments that may have compromised the health of a normal T-cell.

Because the patient has had so many chemotherapies the chances of getting a healthy T-cell are actually pretty low, he said. There are 20-30 percent of patients that go for CAR-T therapy and they get into the clinic and get their blood taken out and then it takes six weeks to generate autologous CAR-T therapy but they cant do it because theres not enough starting material, not enough healthy cells.

This approach of using donor T-cells gets around this problem but Kabakibi believes that it also solves the problem of the skyrocketing cost of CAR-T therapies.

You dont get the economies of scale [with CAR-T using autologous approach,] he said. Thats why you have to be able to generate hundreds of doses and not from the patient, but from a normal patient. You need an off-the-shelf, allogenic version. You take the cells from a normal person and generate a hundred vials that could be shipped overnight to a patient and then that person can be treated in a few days.

Wotton, the CEO of Obsidian Therapeutics, echoed Kabakibi.

You have to find a way to drive down that cost of goods. The way science is going to address that I think is to have off-the-shelf approaches where you can grow billions of cells from a single cell, engineer it to be able to get it to all of us to treat whatever it is we are suffering from, Wotton said. It is much better to build that scale of manufacturing rather than on a patient by patient basis.

Obsidian Therapeutics has developed what it calls destabilizing domain technology to be able to more precisely dose cell and gene therapies.

We are pioneering controllable cell and gene therapies using technology that came out of Stanford University, Wotton said. So in a nutshell, if you give somebody gene therapy today, to produce a particular protein in the body you actually have no idea how much of that protein is going to express. And the same in the case of a CAR-T cell to patients, you actually dont know how many of those cells are going to survive, how quickly they are going to proliferate so being able to dose cell and gene therapies in the same way you can dose a small molecule would be extremely useful.

Obsidianhas a partnership with Celgene through which Celgene can in-license global rights to cell therapy product candidates developed by Obsidian that incorporate destabilizing domain-regulated interleukin 12 or CD40L to fight cancer. Obdisial is using an allogeneic approach.

Our goal in life is to turn cell therapy into the first line of treatment instead of the last line of treatment, Wotton said. The only way you are going to be able to do that is to provide a cell therapeutic that is off-the-shelf, readily available and easy for patients to access, which is actually the approach that we are trying to take.

However, he added that there has to be a balance between cost and value when it comes to novel treatment.

Kabakibi of Wugen Therapeutics agreed.

If you are generating a 100 vials of CAR-T cells, is the price going to drop by 100 percent? Unlikely, he said. I think some therapies will never be as inexpensive as a pill.

Photo: champc, Getty Images

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Makers of novel cell/gene therapy say off-the-shelf approach only way to solve pricing woes - MedCity News