November 24, 2020

The Niche

Knoepfler lab stem cell blog

Right To Try law has a big loophole that’s an opening for bad actors

Young man rides piggyback on an old manThere appears to be a big, risky loophole in the relatively new national Right To Try law.

Some folks apparently anticipated this problem long ago, but I think most of us weren’t aware of it. Update: More specifically, some law and policy experts were writing about this and other potential loopholes in 2018. I recommend this piece from Beth Roxland and Elisa A. Hurley on the The PRIM&R blog.

What’s the deal?

It seems to be a case of what I would call piggybacking that could be a big opening for what the FDA has labelled “bad actors” including certain unproven stem cell clinics.

Keep in mind that the apparent core safety mechanism of this national Right to Try law is the requirement for an existing FDA-cleared investigational new drug (IND) and Phase I data.

That means that the national Right to Try law includes a strict requirement for the treating physician or team to have such a cleared IND and Phase I trial data, right?

Actually, it doesn’t.

The reality of this law instead seems to be that the treating physicians doing a RTT program actually do not need a cleared IND or Phase I data. It is the drug that they propose to use that has to have a cleared IND and have Phase I data.

This isn’t a trivial distinction.

It means that while one specific research team may have done all the work to get the cleared IND and run a Phase I trial, someone entirely different, perhaps in some cases even an individual doctor with no experience in using the investigational drug or even in the general area of the clinical research or the type of medicine needed for the specific patients, could then in theory use the same drug themselves on patients in a RTT context.

So, for example, if a Chicago research team has developed “Drug X” (a kind of autologous stem cells, let’s say) that is part of an IND cleared program and has Phase I data, then an entirely different group that we’ll call the New York team may be eligible for RTT use of Drug X.

And that New York team or doctor could be just about anybody.

As long as the New York doctor is licensed and in good standing in their state, from a national RTT perspective it doesn’t seem to matter who they are, their training, or anything else. Apparently the national RTT law defines eligible patients and eligible drugs, but has little to say about what it means to be an eligible doctor or research program. (State RTT laws are somewhat different.)

This is the big risky loophole in the law, perhaps an intentional one.

I asked FDA and biologics regulatory oversight expert Professor Patti Zettler from The Ohio State University Moritz College of Law for her thoughts on this potential loophole and gave her the hypothetical example of an investigational bone marrow drug product being used in RTT:

“In general, it is correct that, under the federal law, to be eligible for “right to try,” an investigational drug must be one for which a Phase 1 trial is complete and one that is subject to an active IND and is actively under development. The law does not say that the person or entity providing the drug for right to try must be the same as the person or entity holding the IND or conducting the clinical trials.
You raise an interesting question as to whether this creates a loophole of sorts, where someone not involved with the IND could manufacture the “same” drug—and escape the IND requirement in that way. With a small molecule drug, I think the answer should clearly be “no.” If manufacturer A produces Drug A, and only manufacturer A’s drug A is subject to its IND—that is the only drug eligible for “right to try.” If manufacturer B makes a separate version of Drug A, that would be a separate drug, not subject to manufacturer A’s IND and not eligible for “right to try” (until and unless it satisfied the criteria in the statute). In other words, the “right to try” law, as I read it, is not permission for manufacturers to make and distribute copies of products their competitors are researching, simply because their competitor has an IND. With something like a bone marrow derived autologous product, perhaps the question is a bit trickier, because manufacturing isn’t the same as with traditional small molecule drugs. But I think the same logic should apply—that is, only those products covered by the IND would be eligible for “right to try.”
Of course, only time will tell as to whether FDA would enforce in such scenarios, but it seems to me that it could.”

So there is an opening here for RTT programs that are often not in patients’ best interests.

It also perhaps means that, for instance, our hypothetical New York doctor could administer what they see as their version of the biological Drug X to patients under the auspices of national RTT even though it’s possible it might not be exactly the same thing as what the Chicago team has in their IND-cleared program. But let’s say the New York doctor calls it the same drug. Would the FDA view that as acceptable? Like Zettler, I doubt it, but even if we’re right then what happens?  Can the agency try to pull things back after a specific RTT program already got going? Even if it could do that, would it? Would politics come into play?

Also, who decides if it is the “same drug”? The doctor proposing the RTT use of it? The FDA? Remember that FDA doesn’t necessarily get much of a chance to vet RTT arrangements.

One can also imagine some unproven stem cell clinic doctors, maybe even some who have had problems with the FDA and that again the FDA calls “bad actors” trying to take advantage of this loophole to piggyback on a different firm or university’s IND/Phase I data to claim RTT-based use of what they call “the same drug” in their for-profit clinic. That can’t be good for patients. To be clear I’m not questioning patient autonomy when facing a fatal illness, but rather I’m concerned they will be used for profit in some cases. Not all of the risk from this RTT law comes from “bad actors”. Some others may accidentally put patients at risk via the law’s loophole.

Some of this is likely already happening right now. Check out this new piece in Cell Stem Cell by Doug Sipp, Leigh Turner, and John Rasko, which documents some concerning instances of marketing related to RTT already.

The financial side of this is also potentially problematic. While in a RTT context legally a firm can only charge patients the cost of the drug product (again in our hypothetical scenario we’re using the example of some experimental stem cell product), it seems perhaps they can try to add on other costs too. For example, while a patient may “only” pay $3,000 for the investigational stem cells in such a RTT scenario, the clinic could require another $13,500 in supposed essential costs to boost profits.

Overall, I believe the national RTT law has the potential to harm many patients, perhaps far more than it might help. Patients with fatal illnesses such as ALS and Huntington’s need options. The FDA’s current expanded access/compassionate use program isn’t perfect, but it has improved and it gives patients options. If some folks still feel we need a mechanism beyond compassionate use, I don’t see this national RTT law as being the wise option in part because of the big loophole.

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