Federal “right to try” is law! Now what?

Federal “right to try” is law! Now what?

Last week, Pres. Trump signed the federal right to try law. So what happens next? Meaning, who is it going to affect and how big of a difference is it going to make in the lives of the terminally ill and those without any other therapeutic option.

Why a federal law was needed?

As most of you know, a majority of states have already passed a right to try law. The problem with just having the law on a state level is that the state laws were inconsistent with federal law, in the same way as state medical marijuana laws are inconsistent with the federal DEA drug laws.

But the inconsistency was much more impactful in the prescription drug context, because as I and others in the field have said, the drug companies wouldn’t want to anger the FDA by providing their investigational drugs in violation of federal law, even it was supposedly legal under a state’s law.

A good rule to follow for a drug company seeking FDA approval is not to piss-off the agency which has all but unreviewable power to grant, deny or delay marketing approval. A federal right to try law technically obviates the inconsistency. So for drug companies which wanted to provide investigational drugs beyond clinical trials and expanded access, an important impediment has been removed, in theory at least. (And as discussed later, it’s not clear to me why any drug company wants this law or will use it.)

What are the requirements?

Here is the new statute:
https://www.congress.gov/bill/115th-congress/senate-bill/204/text?q=%7B%22search%22%3A%5B%22S+204%22%5D%7D&r=1

Patient eligibility: the law applies to a person with a “life-threatening disease or condition,” which the FDA defines narrowly as “where the likelihood of death is high unless the course of the disease is interrupted and “where the end point of clinical trial analysis is survival.” (21 CFR 312.82). It is interesting to note that this regulation also defines “severely debilitating” as a disease or condition that causes major irreversible morbidity.” But the law doesn’t apply to people with conditions like MS or any other severely debilitating diseases or conditions, since the likely result of MS and other seriously debilitating diseases is not death, and the purpose or clinical trial analysis is not survival in these types of clinical trials.

The bottom line is that the law does really only apply to patients who have a terminal illness and who have no other treatment options. Think metastatic cancer and maybe ALS (and I’m sure there are other diseases, but I’ll leave that to the docs to figure that out.)

The law also prohibits the doc certifying the terminal condition from receiving direct compensation for the drug manufacturer. And of course, proper informed consent is required, but that always a requirement with investigational drugs.

Requirements for the drug

Most importantly: the drug has to have gone through an FDA approved Phase I clinical trial. Phase 1 is usually a small toxicity study, the goal of which is to make sure that the drug isn’t too toxic to administer to patients at the expected therapeutic dosage.

Phase 1 studies do not have to show efficacy; however, a drug which shows zero efficacy might not create much enthusiasm from the sponsoring drug company to justify the cost of further study. And I would think that most people might want to see at least some benefit, however small, from a study, or at least some anecdotal evidence of some positive result. My sense is that many drugs which have passed through phase 1 can show at least some marginal improvement in some subjects. This is the case despite the fact that the overwhelming majority of post phase 1 drugs don’t get approved. (And there are a lot of reasons for that, including the obvious that the drug doesn’t work, or doesn’t work in a high enough percentage of subjects).

The post phase 1 drug must also be in active development and not be on a clinical hold.

Requirements of the drug sponsor/manufacturer

There are three requirements imposed on the sponsor, two are simple: the drugs have to be properly labeled as investigational, which is easy because the drug was already given in a phase 1 study and the drug label had already been approved by the FDA. (A small change in the label might be required.)

Second, the sponsor can’t promote the safety or efficacy of the drug, but a sponsor is not allowed to do that in clinical trials either. So the sponsor doesn’t have to do anything different from its actions (non-actions) in the clinical trial.

Third, the sponsor at most can recover the direct costs of the drug provided to the patient, but that’s a narrow and parsimonious amount of money. I read the statute as not requiring an accountant’s certified statement supporting the cost recovery which is the case when a sponsor wants to cost recover for patients in clinical trials. The bad news (for the drug company) is that the direct costs for each patient is likely to be an insignificant number as it doesn’t include the drug’s development costs. So I don’t see many drug companies charging for the investigational drug.

Protections for the sponsor/prescriber

If the sponsor and prescriber follows the law, they can’t be sued for simple negligence, but they can be sued for alleged reckless or willful misconduct, gross negligence or an intentional tort under state law. Practically speaking, that’s not all that much protection since it’s easy to allege facts which show more than simple negligence. But it’s something.

Reporting results of the right to try use

The manufacturer or sponsor has to provide an annual summary of the use and serious adverse events. (Adverse events don’t require a causal connection to the drug, just a temporal association.)

Can the FDA use the serious adverse in evaluating the sponsor’s new drug application?
Yes, but only if the FDA determines that the use of the data is critical in determining the safety of the drug. That’s pretty broad. I would expect that if the drug is producing many serious adverse events, beyond what was reported in the results of the regular clinical trials, these data will be carefully looked at by the FDA.

The good news for sponsors

The statute specifically states that drug manufacturers do not have to provide investigational drugs pursuant to the law, and can’t be liable for not doing so.

Why is that good news for them?

I am hard pressed to think why any manufacturer involved in clinical trials would agree to provide its drug under this law. All I see is downside. The patients likely to want its drug are probably a lot sicker than the subjects it selected via entry criteria to get the drug on the study. The sicker the patient, the more serious adverse events which may or may not have been caused by the study drug, but as indicated, adverse events aren’t about causation, just a temporal association. Drug sponsors try to stack the deck in their favor by treating the healthiest patients than can with the condition. Why stack the deck the other way?

I can only think of two circumstances where that would make sense.

First, the results of the phase 1 study are so spectacular and the company lacks the funds to do further clinical studies. It might make sense to push a lot of people onto the treatment to amass more spectacular data.

Second, a sponsor/manufacturer is a physician and the business model involves providing an investigational drug to patients. But that’s a very rare model in the U.S.

The bottom line is that I don’t think many drug companies will voluntarily use this law. Frankly, if I was asked to advise a company about it, I’d tell them not to do so other than the two above circumstances because I just see downside. I know that sounds harsh, but the main job of a drug company developing a new drug is getting it approved. Anything that helps that process should be pursued. Anything that doesn’t, could hurt, or distracts from approval shouldn’t.

The law ends with something I’ve never seen before, a section entitled “Sense of the Senate.”

It’s so strange, I’ll let it speak for itself:

“SEC. 3. SENSE OF THE SENATE.
It is the sense of the Senate that section 561B of the Federal Food, Drug, and Cosmetic Act, as added by section 2—
(1) does not establish a new entitlement or modify an existing entitlement, or otherwise establish a positive right to any party or individual;
(2) does not establish any new mandates, directives, or additional regulations;
(3) only expands the scope of individual liberty and agency among patients, in limited circumstances;
(4) is consistent with, and will act as an alternative pathway alongside, existing expanded access policies of the Food and Drug Administration;
(5) will not, and cannot, create a cure or effective therapy where none exists;
(6) recognizes that the eligible terminally ill patient population often consists of those patients with the highest risk of mortality, and use of experimental treatments under the criteria and procedure described in such section 561A involves an informed assumption of risk; and
(7) establishes national standards and rules by which investigational drugs may be provided to terminally ill patients.”

I’m not sure what it means or why its in the bill, but I like.

Congrats to the Goldwater Institute and all the supporters who made it happen. Hope it helps, and from my perspective, it’s moving in the right direction.

In case you folks are looking for the next thing. Maybe access to some foreign approved drugs for terminal or severely debilitating conditions.

Rick Jaffe, Esq.
www.rickjaffe.com
rickjaffeesquire@gmail.com

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