A new right-to-try company called Beacon of Hope is stirring some intense discussion. State and federal right-to-try laws could potentially change the fabric of how many investigational studies are conducted. That may happen through firms like Beacon of Hope. However, we don’t know much about the firm. I’m hoping to help change that.
Today’s post includes a detailed interview with the leader of Beacon of Hope, Richard Garr. For background, Garr was formerly CEO at Neuralstem. During his tenure at Neuralstem it became well-known in the stem cell community for its trial for ALS, and participant Ted Harada drew national attention.
What’s his new effort Beacon of Hope all about?
Here’s my conversation with Garr.
What exactly is Beacon of Hope CRO? Is it a for-profit company?
RG: Bohcro is the first CRO dedicated exclusively to facilitating Right to Try programs, at scale, for the industry. Yes, while we provide access for patients to RTT treatment programs, we work for the drug developers like any CRO, and we are paid by them, and only by them, and yes we are a for profit company. We are also focused on fusing the Right to Try treatment programs with the collection of RWD through a proprietary system to accelerate development timelines and significantly reduce development costs.
Right now I only see you listed as an employee. Do you have other team members now and if so, who are they? If not, do you plan to bring other people on soon and will you have a Board?
RG: Bohcro is a “near virtual” company. We have a core group of employees, and try to do as much as possible through strategic relationships and outsourcing. Our largest partner is an international, traditional clinical CRO which provides resources on an as needed basis. Similar to the way we built my last company, there will come a time when we will have to bring some additional functions in house.
On your website it says this in regard to payments, “Physicians and other service providers can be paid under Right to Try. Under the Act patients can only be charged the “cost” for the actual drug if they are charged for it at all. In most instances it is assumed the drug will be provided at the sponsor’s expense as in a traditional clinical trial. At Beacon of Hope we will also be administering programs that are “patient pay” for services and possibly even for the drug as well as programs that look more like traditional sponsor funded studies.” Can you clarify how this will work and will you do any non-RTT programs?
RG: Beacon is exclusively dedicated to implementing RTT treatment programs, we will not do any programs which are not RTT compliant.
Sec 312.8 of Title 21 lays out the FDA’s rules for a sponsor charging for a drug under an IND in sections A through D, These rules also apply to the FDA’s traditional expanded access programs. S. 204 (the Right to Try Act) specifically incorporates only 312.8 (d) (1) which defines what can be charged. The concept is basically one of actual, direct cost. This amount is, literally, no different than what can be charged to a patient under any of the FDA’s traditional trials or expanded access programs. The allowable cost will be determined in the exact same manner that it is determined under any FDA program. Yes, this is somewhat of a forensic accounting exercise, but it is not unusual nor difficult, and there is tons of history and opinions and guidances etc. in the area.
How will the efforts of Beacon of Hope be similar or different from Wide Trial?
RG: I am a big fan of Jess’s work and dedication to the field; but I know very little about his business plan or operation, nor would I comment on another company even if I did. I can tell you that I believe that all flavors of expanded access, whether traditional (which I believe he is focused on) or via Right to Try are going to become the norm in drug development. One big difference however which I can comment on is that the FDA’s traditional expanded access program is not limited to life threatening diseases or conditions, Right to Try is. And as I have said, Beacon is exclusively dedicated to Right to Try.
Do you plan to get IRB approval at times for the RTT activities even though it’s not required? Why or why not?
RG: So to be clear, Beacon does not “get” IRB approval (or not). Sponsors do. The Right to Try law does not require an IRB approval in order to be a compliant program. However, Right to Try does require that an eligible drug have already passed at least one FDA approved phase one trial, and be in active development under an IND. So I have yet to start a program, or even speak with a potential client, that does not have an IRB approved protocol, nor can I imagine a situation where they wouldn’t. In the unlikely event that a client has an IRB approval but decides that they don’t want to treat the RTT patient under that approval; that fact, and whatever differences there might be, would be explained to the patient and the patient’s doctor in the normal patient information and consent process; and as was the intent of the law, the decision to proceed or not remains in the patient’s hands in consultation with his/her doctor.
Since no FDA approval is required, who decides if a particular RTT offering has an acceptable foundation (such as initial data) to initiate its RTT-based use in patients? Can you imagine Beacon of Hope rejecting certain proposed RTT treatments and if so, what might trigger such a rejection?
So S.204 “decides” if a particular RTT offering has an acceptable foundation. It lays out the conditions for a compliant program both in terms of an eligible drug and an eligible patient. While the FDA does not “approve” a treatment under Right to Try, they are the sole arbiter under the law, of what is or isn’t an eligible drug. The drugs are, by definition, the exact same drugs that are being given to patients in mid and late stage FDA trials, and if the FDA were to halt a trial, for any reason actually, not just safety, the drug would no longer meet the definition of an eligible drug.
The question of whether or not someone determines if the scientific rational or a specific mechanism of action justifies a drugs development, is always one that is made at first by the Sponsor. Again, these are the same drugs in development under an IND. If the FDA believed that the safety risk vs. possible efficacy calculation didn’t warrant approving a trial, they wouldn’t, and at that point the drug would not be eligible for Right to Try.
To answer the final part of your question, Bohcro is a private company and we do not have to work for anyone. It is not our job to second guess the FDA or the RTT law, but of course we reserve the right to do so.
Since you are the former leader of a stem cell biotech company, people are naturally wondering the following: will Beacon of Hope be involved with patients accessing investigational stem cell therapies? Would your company work with for-profit, unproven stem cell clinic firms that produces stem cell products?
RG: So yes, because of my background and strong interest in both the stem cell field and in trying to help the ALS community BOHCRO does have now and expects to have in the future multiple stem cell therapies to treat multiple life threatening diseases. Again, the qualification, or eligibility for an RTT compliant therapy is laid out in the law; and continued eligibility requires continued product development under an FDA IND. My guess is that the “bad actors” in the stem cell field that you are referring to do not fall under that umbrella. I would however, imagine that all of our clients will be for profit companies, whether they are developing stem cell products or drugs.
Since there is some immunity from potential lawsuits against sponsors, who or what protects the patients, especially if for a particular RTT offering things go unexpectedly badly? Will you have a bioethicist as part of your team given the complexities of all of this?
RG: First, the partial immunity is not just for the sponsors but basically the entire ecosystem including the doctors. This was included in the law specifically as an incentive to try create more access for more patients; and at BOHCRO we spend a good amount of time making sure that patients understand the possible rights they may be giving up. While this is an area of Federal preemption, there are 41 state RTT laws that have been enacted also, and each of them addresses the area of immunity a little differently, and it’s important that patients understand all of that. So the law, and certainly any programs that we run, relies on transparency and informed consent to protect patients; and it also relies on the patient’s doctors. A fundamental tenant of this law is that the ultimate decision lies with the patient and their doctor.
What are your expectations in terms of your firm facilitating the generation of strong data? How is that possible since there’ll be few subjects, no controls or blinding, and there’s definite potential for bias in the structure?
There are several ways in which the concepts behind adaptive trials and real-world data can impact the cost and time of drug development. When you remove (what I will call) the FDA overlay the process becomes significantly quicker and cheaper. How meaningful the data you end up with is, depends on what you are looking for and what you need the data for. For example, I am talking to a client that will be treating an “eligible” disease, but is losing roughly 50% of his trial recruits because they are all experimenting with various CBD products for chronic pain. His ongoing mid stage trial is going to take twice and long (and cost twice as much) because of that. There is no reason to believe that CBD causes a safety issue. Under RTT he can treat the “screen fails” and see if there is any difference between that group and his trial group and that will inform his trial design for the really expensive pivotal trial to come. And depending on his decision there, he still may use that RTT data in lieu of a phase 4 trial when discussing labels and reimbursement with payers. Again saving significant time and money over doing a phase 4 trial after approval.
Another example, where I can give you some detail on the data collection is ALS. Everyone uses various functional scores and tries to show some statistically significant “slowing” down of the downward curve from the disease. Serious people in the field are starting to question the scale, but it’s “validated”. In a real-world data collection program, where we have created custom “pages” and using remote collection; we can measure things like: is the patient still alive? Mortality being the ultimate biomarker over time. Is the patient still ambulatory (if they were prior to the treatment)? Time to a wheel chair is a huge quality of life issued for ALS patients. Is the patient reliant on invasive breathing assistance? Again, time to invasive breathing assistance is a very important end point, although the FDA has not acknowledged that it can be The endpoint for approval in a trial. The ALSFRS-r is the only validated end point for approval so far. But we can collect this other meaningful data, in an incredibly cost efficient and accurate way; and a sponsor will know if they are really impacting the disease in a meaningful way.
When most people talk about RWD they are thinking of dipping into existing pools of data; going backwards in time. Everyone thinks there is gold in those mines. Perhaps there is. But I think the technology (hardware and software) has outpaced the ability to use it. We are talking about using that same technology in a perturbed system, the RTT treated patients. No, the FDA has not yet passed final guidelines on how they will ultimately allow sponsors to use this information; it’s probably another year to two away. And as always, the value on any data is dependent on the quality of the data. But drug developers KNOW what they don’t know, and they know how to look for it in a safe way. Being able to get that information and controlling it completely, is going to create a powerful incentive to participate in RTT programs. The same will be true across many fields/indications. I have spoken to biotech cancer CEO’s who are trying to decide between 8 or 9 possible “combo” trial arms, but can’t afford it. They can do RTT and look for a signal and then spend the money on the best choices. At least that is what I believe. We all spend as much time as we can trying to “manage” our trial population to maximize the potential trial value, regardless of our eventual intent to treat population. That’s simply the economics of drug development. RTT gives you a way to avoid that trap and learn what you really need to know, sooner and quicker. And in so providing that incentive RTT allows patients to gain access to investigational medicines.
RG: Just think about the numbers, and history. Again I’ll use ALS as an example. Less than 1% of ALS patients have meaningful access to an ALS trial. (Not even taking into account the control arm here and actual access to the drug). So when you ask “why is the RTT effort “better” than an EA program, the answer is, as coaches say, the best “ability” is “availability”. The same sad story (different but still low single digit numbers) can be said of all types of cancer trials and other RTT eligible diseases. Among the real reasons that companies have never taken to EA programs (and 1,000 patients over two years, for all indications?) are that if something goes wrong, even if it is outside of the type of patient you would have in your trial, the FDA can stop your trial and delay you indefinitely. NO CEO can take that risk, and the history of EA’s shows that. No matter how much the FDA says they will “take into account” the fact that you are treating different types of patients, they do not relinquish the ability to do exactly that, and effect your trial. How do you quantify that risk if you are a CEO? You can’t, and so you don’t. And you print on clinicaltrials.gov as so many companies do, some form of… “we believe the fastest and best way to get this drug to everyone is focus all our resources on the clinical trials,” and so no.. we have no EA policy.” That is one of the reasons RTT was written so the FDA can’t do that. That is a powerful reason why RTT will create real access.
Also, despite the claims that they have “simplified” the forms, experience shows us that doctors are reluctant to go through the FDA’s process. It was legitimate to ask the question, was that roadblock a necessary patient protection? It has been answered by the passage of the new law, resoundingly, no. The fact that the FDA is not involved in the direct approval of the treatment decision again will have a huge impact on availability. Of course a doctor may not like the idea, and that is fine. The law intends the decision to be made by a patient in concert with their doctor and of course the sponsor.
Finally, although a sponsor has complete control over the data, they CAN share and/or publish it if they want. This gives (especially young and innovative biotechs) a way to create data for milestones outside of the clinical trial cycle which often takes years between milestones; and the ability to raise more money to get to the finish line, or alternatively kill a program much sooner. Will the market discount such data? Who knows, probably, but as with everything else the quality of the data will drive its value. Just like when the FDA or a payer looks at the data to determine how much weight to ascribe to it. I believe it will become almost a “must have” eventually for companies developing drugs; starting with smaller companies and eventually building to the large ones.
I’ll end with this. People argued that doctors and patients with life threatening diseases will all just say “what the hell I’ve nothing to lose” and so needed “extra” layers of protection. As the father of a child who has fought brain tumors all of his life, I can tell you that’s not true. John Glass, at Emory who was one of my PI’s for ALS and both a man and a doctor and a scientist that I admire tremendously pulled me aside when we started designing our trial and explained to me that he tells every patient considering an ALS trial that that simply is not true. They all have Some quality of life, and it Can be made worse by investigational treatments; maybe even much worse. And so we make sure that that type of informed consent is part of any program that we manage. I can do that because I write the forms.
Anything else we should know?
RG: I just think that sometimes the scale of the “lack of access” to investigational drugs gets lost. ALS is a perfect example. There are what, maybe 500 to 1,000 at most slots that are going to be available for ALS clinical trials in the next year? Not to mention that they are all looking for the same patient in terms of inclusion exclusion criteria. There will be 5,000 to 6,000 newly diagnosed patients over that time, and roughly another 25,000 patients in the existing population. ALL of them will likely die before any of the drugs in other than the latest stage trials now, get through their trials, even if they are successful. So really only a tiny single digit percent of ALS patients have meaningful access to investigational drugs. These patients and their families deserve better. Right to Try was created to encourage more meaningful access and we are trying to help that happen.