As I predicted, the exploitation of desperate patients using right-to-try begins

Well, that didn’t take long.

When last I wrote about the cruel sham and scam known as “right-to-try” concocted by the quackery-friendly for-profit hospital chain the Cancer Treatment Centers of America and foisted on gullible legislators by the libertarian propaganda group disguised as a think tank, the Goldwater Institute, it had just passed Congress thanks to a last minute push by Vice President Mike Pence, President Donald Trump, and, of course, the Koch brothers, I warned about how the unscrupulous could use it to profit off of desperate terminally ill patients. Basically, it legalized at the federal level the practice model of cancer quack Stanislaw Burzynski, whose antineoplastons had passed phase I testing (which, as incredibly low a bar as it is, is required by right-to-try) and is still in phase 2 clinical trials (also a requirement of right-to-try). Also, as you recall, Burzynski built his fortune charging enormous “management fees” for treatment that could run into the hundreds of thousands of dollars. It’s a scam he’s been doing for forty years now, and, unbelievably, is still getting away with.

To be honest, I really didn’t think that I’d be writing about right-to-try again so soon. I really didn’t. After all, it’s been less than two weeks. However, something happened that I warned about, and it happened even faster than I could have imagined in my worst fears. I’ll just lay two headlines on you. The first one is from STAT News by Adam Feuerstein, Here come the right-to-try profiteers. The FDA is powerless to stop them. The second is from Bloomberg News by Michelle Cortez, The ‘Right to Try’ Could Cost Dying Patients a Fortune. Both articles are about BrainStorm Cell Therapeutics, a small biotech company developing a therapy for the deadly neurological condition amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease), a uniformly fatal degenerative neurological disease that tends to strike people over 50.

Before I get to what BrainStorm is doing, first let’s briefly review right-to-try. Basically, it was a scheme dreamed up by a Cancer Treatment Centers of America executive back in 2013. CTCA, if you recall, is a for-profit chain of cancer centers whose business model is to combine quackery (e.g., naturopathic oncology) with real medicine that is also known to inflate its outcome figures through cherry picked data. This executive took the idea to the libertarian propagandists at the right wing bill mill known as the Goldwater Institute, which came up with the very salable name “right-to-try” and wrote some model legislation. That task done, the Goldwater Institute proceeded to promote this model legislation, beginning in Colorado, where it passed in 2014. Since then, right-to-try laws have been spreading like kudzu to the point where 40 states now have them.

State-level right-to-try laws all have several features in common, based on the Goldwater Institute legislative template. First, as I mention above, the idea is to allow terminally ill patients the “right to try” experimental therapeutics. The experimental drug must have (1) passed through phase I trials and (2) still be in clinical trials for FDA approval. Although Goldwater Institute flacks have made the claim on numerous occasions that this guarantees that the experimental therapeutics are “safe,” but that claim is utter nonsense to anyone who knows anything about how clinical trials work. Phase I trials, after all, usually involve less than 30 people and are designed to determine the maximal tolerated dose and to screen new drugs for toxicity and adverse reactions too severe to justify continued testing. Right-to-try laws purport to allow terminally ill patients (defined somewhat differently, depending upon the state and the law) to obtain experimental drug right from the company making it. The company may agree to the request or refuse it. Most right-to-try laws allow the company to charge for the drug. These laws also protect doctors, companies, pharmacies, and anyone else involved in a right-to-try transaction from any sort of liability related to it, as well as explicitly exempting insurance companies from paying for such treatments. (Indeed, the language of some laws, as I’ve discussed before, could be interpreted as allowing insurance companies to refuse to pay for treatment related to complications related to a right-to-try drug.) Basically, “right-to-try” has been more properly called “right-to-ask” because the law doesn’t obligate companies to actually supply the drug. Worse, these laws basically leave patients entirely on their own, potentially paying huge sums of money for unproven medications because, of course, there is no requirement that companies provide the drug for free.

The key problem, with right-to-try laws was that they addressed a problem that didn’t exist and addressed it badly. After all, the FDA already has expanded access programs that approve something like 98% of requests without stripping protections from patients, such as oversight by an institutional review board (IRB). Of course, the key problem with state right-to-try laws from the perspective of the Goldwater Institute was that the FDA still controls drug approval. In other words, federal law overrides state law, and most companies would be very loathe to cross the FDA by letting patients have their experimental drugs outside of the auspices of a clinical trial whose purpose is to produce evidence of efficacy and safety that can be used as part of an application for drug approval.

Enter federal right-to-try, which was passed last month and signed into law. Basically, this law has the same sorts of provisions as state laws (phase I trials, no liability, patients can be made to pay) plus some federal-specific aspects. The worst of these provisions is this. The FDA Commissioner cannot use outcomes from right-to-try drug use in his consideration of whether to approve a new drug for market unless the sponsor (drug company) requests it or the Secretary of Health and Human Services determines that such outcomes are “critical to determining the safety of the eligible investigational drug.” In this case the HHS Secretary must justify this decision in writing. The HHS Secretary can also delegate this decision no lower than to the director of the relevant agency in the FDA in charge of approving the drug under consideration. Anyone want to guess how willing the HHS Secretary will be to do this very often?

I speculated that quacks would love this law, but cautioned some of the zealous opponents of right-to-try that few quacks would be able to take advantage of it because few are the quacks whose treatments have passed phase I clinical trial testing. In this, Burzynski is an exception. On the other hand, that doesn’t mean that the potential for abuse doesn’t exist:

A small biotechnology company may be the first to offer dying patients unproven drugs under a new U.S. law called Right to Try that deregulated access to such experimental treatments.

But it won’t be for free: Brainstorm Cell Therapeutics Inc. would charge for a therapy it is developing for the deadly condition known as Lou Gehrig’s disease. While details are still being worked out, the company’s chief executive officer pointed to the price of bespoke cell therapies used to treat cancer that cost more than $300,000.

“Companies cannot be NGOs,” the nongovernmental organizations that help provide care to impoverished countries, Brainstorm CEO Chaim Lebovits said in a phone interview. “We have to have an incentive.”

If it decides to proceed, Brainstorm — a company with no drug on the market yet and no revenue — would introduce a profit motive into an effort many expected to be altruistic, adding more controversy to an already contentious debate. Small drugmakers where much of the innovation in medicine originates can’t afford to provide their compounds for free, and terminally ill patients with no other options may be eager to pay for access. There would be little protection for patients already grappling with a tumultuous time in their lives, adding financial risk to the known medical gamble.

But what is BrainStorm’s treatment? The company calls it NurOwn®. I have to admit that looking over the company’s website I immediately had my doubts about it. It reeks of dubious stem cell treatments, quackery even. Check out the page on this treatment and see if you don’t share my concerns. Basically, BrainStorm uses mesenchymal stem cells (MSCs). I note that two of the clinics that the FDA has cracked down on for their practices advertise MSCs. Indeed, Stemedica, the company that took advantage of the family of Gordie Howe to promote a stem cell-based treatment for stroke, also claims it was using MSCs to treat stroke. To be fair, just because quack stem cell clinics claim to be using MSCs to treat all manner of diseases doesn’t mean that BrainStorm isn’t on to something, but I must admit that I find the scientific justification for its ALS treatment to be rather spotty:

Where others leave off with MSCs, BrainStorm begins. Our patented NurOwn® technology takes MSCs and, by growing them in proprietary conditions, converts them into biological factories secreting a variety of neurotrophic factors (NTFs). NTFs are growth factors known to support the survival of neurons in a variety of conditions, and in animal models of many neurodegenerative diseases.

The NurOwn® technology was developed in the laboratories of Professor Dani Offen and the late Professor Eldad Melamed, at Tel Aviv University, and has been the subject of many publications. Our NTF-secreting MSCs (or, MSC-NTF cells) are designed specifically to treat neurodegenerative diseases by allowing us to deliver several NTFs at or close to the site of injury.

There’s a list of publications, but none of the links actually go to publications on the main page. It took multiple clicks to get to many of the publications. For instance, there is a phase I trial that shows a single dose of MSCs was safe. There’s also a phase 1/2a clinical trial carried out at Hadassah Medical Center in Jerusalem that suggests an effect on two measures of ALS progression at a marginally statistically significant level that are probably transient. Is there something there? Maybe. Even though the scientific justification seems to be a bit of handwaving, with genetically engineered MSCs basically making a bunch of growth factors for neurons seemingly without a lot of careful targeting based on the pathophysiology of ALS, maybe it’s worth doing phase III clinical trials on. However, one thing I will say for sure is that it is not worth paying for before phase III trials show it to be efficacious and safe, with a clinically meaningful effect in ALS patients. Fierce Biotech notes that there is also a phase 2 trial that “found limited evidence of efficacy, with placebo matching NurOwn on measures of lung function and ALS progression.” Basically, the phase 2 trial NurOwn was unable to slow the progression of ALS compared to placebo, leading the company to start doing a responder analysis to try to find a signal indicating efficacy.

To me the existing evidence of efficacy for NurOwn is barely enough to justify continuing with a phase III trial, but apparently BrainStorm disagrees.

Or BrainStorm is looking for money wherever it can get it to continue to fund its product development:

Brainstorm, listed in the U.S. and run from New York and Israel, is trying to address the tension head-on. After requests for access to Brainstorm’s NurOwn experimental drug came pouring in following the passage of Right to Try, the company held conference calls with patients and investors to talk through details.

Only doctors who participated in the drug’s clinical trials would be included in the Right to Try program under consideration at Brainstorm, CEO Lebovits said. It would be a semicommercial enterprise with modest profits that wouldn’t exploit patients’ desperation, he said. The company, which had operating costs of $5 million last year, would work to obtain funding from foundations or other charitable organizations to help pay for at least one financially strapped patient for every two who are able to pay for it, he said.

Lebovitz says this venture wouldn’t exploit patients’ desperation, but how does he know that? I don’t know about you, but to me the very fact that his company will be selling an unproven treatment to patients with a terminal illness based on a marginally promising phase 2 trial indicates that the company will be exploiting desperate patients. This is even more true given that the treatment could carry a similar cost to recently approved cell therapies known as CAR-Ts, which are tailored for each patient by isolating the patient’s T cells and genetically engineered to produce chimeric antigen receptors, or CARs, in a similar but more complex way than how BrainStorm engineers NurOwn from the stem cells isolated from each patient. The cost of CAR-T treatment? Roughly between $375,000 and $475,000. So what we’re talking about here is the possibility that terminally ill patients with ALS could be paying the cost of a house for a treatment that hasn’t even been shown to be effective in anything resembling a convincing manner yet.

Yes, it’s nice that BrainStorm will try to obtain foundation funding to pay for around a third of the patients requesting its treatment under right-to-try, but that’s not nearly enough. In fairness, I also note that there is a provision in the new federal right-to-try law that limits what companies can charge to “direct” costs only. But what does that mean? Who is going to audit BrainStorm’s books to make sure that only direct costs are charged to patients. I can’t help but point out that the BrainStem CEO himself said that the intent is to make a “modest profit.”

Proponents of right-to-try, like Sen. Ron Johnson, who sponsored the bill that is now law, claimed that it wouldn’t permit this, but who’s going to stop BrainStem? The FDA? There’s no real mechanism for enforcement of the provision in right-to-try that supposedly bans companies from charging more than “direct costs,” and I highly doubt that the FDA will want to be too aggressive here. Why? Do you remember what happened when FDA Commissioner Dr. Scott Gottlieb expressed support and a willingness of FDA to work with right-to-try to protect patients seeking drugs under the new mechanism? Let’s recap.

It didn’t go well—for Dr. Gottlieb.

Basically, the law’s primary sponsor, Sen. Ron Johnson, slapped Dr. Gottlieb down so hard that that he’ll be digging himself out for a long, long time. The beatdown came in the form of a letter that made the intent of right-to-try very, very clear:

As I made clear to my colleagues in the Senate and the House before each body voted on S. 204, this legislation is fundamentally about empowering patients to make decisions in cooperation with their doctors and the developers of potentially life-saving therapies. This law intends to diminish the FDA’s power over people’s lives, not increase it.

Poor Dr. Gottlieb. He thought that right-to-try was about expanding access to promising therapeutic agents and not about emasculating the FDA. Well, Sen. Johnson sure set him straight, and because Sen. Johnson set Dr. Gottlieb straight I highly doubt that Dr. Gottlieb will be too enthusiastic about being too aggressive going after companies like BrainStorm looking to profit (whether “modestly” or otherwise) from right-to-try.

BrainStorm is just the pioneer. It’s the first company out of the gate, testing the limits of right-to-try. Given the fiercely anti-regulatory nature of the Trump administration and Congress, it is very likely that BrainStorm will get away with doing whatever it wishes selling its unproven stem cell treatment for ALS under right-to-try. If it does, you can count on a lot of biotech startups and other pharmaceutical companies emulating BrainStorm and getting away with it. Trust me, quack stem cell companies that have done phase I trials on their quackery are chomping at the bit to follow BrainStorm’s example.

Never mind how many patients go bankrupt or suffer grave harms pursuing an experimental therapy that is incredibly unlikely to prolong their lives.