The Rare Disease Patient Voice Created Endpoints with Impact

What is the work you’re leading at the Gorlin Syndrome Alliance?

We have a number of things going on at this point. As always, our first priority is providing support to individuals and families with Gorlin syndrome. The next big ticket item we have right now is on October 8, we’re doing an Externally Led Patient-Focused Drug Development (PFDD) meeting for the FDA.

This is really an opportunity of a lifetime for us to teach them about what Gorlin syndrome is, the burdens and the unmet needs, and what would make our lives better. We hope it will make a huge difference in drug development and the FDA’s recognition of our issues, our problems. We are also currently assisting in recruitment for clinical trials and preparing for 2022 when we hope more trials will begin. We’re working with pharmaceutical companies on that.

"You do not know what life is like for somebody with a rare disease, particularly one that can affect every organ system. From our partnership with LEO came the phrase, “Nothing about you without you.” 

One of your pharma partnerships is with LEO Pharma. Can you describe that collaboration, and any other partnerships you’ve had?

One of the most burdensome manifestations of Gorlin syndrome is that we get multiple basal cell carcinomas. I’ve had over 1000 basal cell carcinomas removed. We were heavily involved with them, after the trial protocol was written, in assisting with recruiting patients. We had record-setting recruitment with that. We also assisted with retaining participants in the trial.

That trial unfortunately did not meet its endpoints. There were specific numbers, in terms of percentage response, that the trial needed to reach and it didn’t get there. That was hugely devastating for our community, because for some people, their response to the topical product was life changing.

They went from having skin cancer surgery on 20 or more lesions in a year to, over the course of two years, not needing any skin cancer surgery on their face, neck or scalp. That’s huge.

Is that type of feedback that you might pass along to the FDA?

It’s just part of what we hope will come out of our PFDD meeting, and all our communications because I feel strongly that there needs to be some regulatory flexibility when the FDA looks at rare diseases. Let’s say we had a product for hypertension, and had a response rate for a new product of 30%. That’s not very much; that’s not very good. But if in a rare disease, to have a 30% reduction in your number of skin cancers that you develop over a one-year period, that’s a big number for somebody like me.

So I think the recognition of the burdens as well as regulatory flexibility needs to be applied to all rare diseases, particularly ours in this situation, because it will make a positive impact on our lives, on every level. Using FDA lingo that I learned recently, it will be clinically meaningful in that there will be significant improvement in how we feel, function, and survive.

It’s a point that we have stressed with other companies, and we will continue to do so. Again, regulatory flexibility is essential, because those numbers are huge. The challenge is getting the FDA to approve a protocol with endpoints that are, in our minds, reasonable. And to me, reasonable is 30%. But in many cases, it must be 50% or higher. And, again, I go back to the example of a person that I know who went from having no basal cell surgery for over two years, while on this trial medication to being back to where he was before, where every three to four months, he’s having multiple basal cells removed.

I get that there’s also a financial component to it. But, this is not something that the FDA evaluates. How much the product is going to cost is another, obviously critical, component to our members. One of the things I look at is the cost of having 30 basal cells removed per year, compared to this drug, or any drug. I am pretty confident that the drug would turn out to be less expensive than the multitude of surgeries required.

How do you determine a successful and impactful pharma partnership?

It has to start in the protocol development, because we need to be able to say, “These are numbers that you need to reach for in terms of endpoints.” We have data from a global survey that ended in early 2020 that shows our burden of disease, in terms of many manifestations, but particularly basal cells. We have data that shows the volume and can show what a percentage reduction would mean. It starts with protocol development, then designing a study to make it reasonable. We’re a community of people. Part of our global survey showed that individuals with Gorlin syndrome spend over 24 days per year either at appointments, surgery or recovery. They have missed that much of their life to all those things. So to add in a clinical trial, where you have to have multiple visits, may not be reasonable. So figuring out how to lower the number of in-person visits is critical.

Then it’s creating inclusion/exclusion criteria that are based on, for example, the number of basal cells that people develop. After that, there’s recruiting patients, retaining them in the trial and meeting with regulatory agencies like the FDA to clarify the positive impact of the product on our community.

Why is it so crucial for pharma groups to work with patients or advocacy organizations?

You do not know what life is like for somebody with a rare disease, particularly one that can affect every organ system. From our partnership with LEO came the phrase, “Nothing about you without you.” For any pharma company to say that they are sure something will make an impact, how do you know? Have you asked us? I feel strongly about “nothing about you without you.” I don’t like it when people speak for me. I’ve had a researcher at one point say to me, “It’s just a basal cell, you can have them cut off.” And I said, “Wait a minute, wait a minute. What if you get 40 or 60 in a year? That’s not that easy.” Don’t make presumptions like that without knowing what it’s like to walk in someone’s shoes.

It’s not just that day of going to have them cut off. It’s the anticipation before. Then it’s the day of having them cut off. Then it’s the recovery which can take months. And if you are a parent, it is the time away from work to take your child to the appointments, the surgeries, and care for them while they recover. It’s how people look at you, how you feel about yourself, how you look, how you sleep. I had one removed from my ear three weeks ago, and I still can’t sleep on the right side of my head.

There are all these factors that come into this – physical and psychosocial and emotional – that need to be considered. And by advocacy groups partnering with pharmaceutical companies, that helps everybody. It helps pharma understand where we’re coming from, and what will be most beneficial for us.

"If you’ve got a good molecule, you’ve got to develop a trial to highlight that product, otherwise, you might as well throw that money away. It’s essential to make it win-win as much as you can."

Have you seen the change in the ways in which pharma companies are willing or accessing patient engagement groups or patient advocacy groups over your time as an advocate?

Definitely, absolutely. They’re much more willing to have us as partners, and that’s really what it has to be for success in the long run. There’s no other way. I can only speak for Gorlin syndrome, and it also depends on the pharmaceutical company. So from my standpoint, the partnerships between advocacy and pharmaceutical companies are essential for trial success. We have a private and secure database; when, for example, when we have a trial that is recruiting, we promote that trial on our website, through all our social media, and at our conferences so that people are given the information on the trial and they make the choice as to whether they seek out more more information on the trial.

In my ideal world, and what is happening more and more, is that pharma is engaging with us to develop a win-win situation. If you’ve got a good molecule, you’ve got to develop a trial to highlight that product, otherwise, you might as well throw that money away. And we all know it’s a huge amount of money. So it’s essential to make it win-win as much as you can. When you have a population of potential participants who are hungry for better treatments, and hungry for a cure, why not go to the advocacy groups that will bring those people to you?

Is there anything you’ve learned about how to partner more effectively with pharma?

What always works best, in my view, is being open, honest and transparent throughout. You have to be careful, because of compliance rules. In the United States, and in Europe, there are certain things you can and can’t say. But one of the things that I’ve done all along has been to be open about saying, “Okay, I know there is a compliance box. Help me stay within the box and not jump outside of it and impair the integrity of the trial.”

"By advocacy groups partnering with pharmaceutical companies, that helps everybody. It helps pharma understand where we’re coming from, and what will be most beneficial for us."

What would be your final message for any advocacy and pharma readers?

For advocacy groups, I would say it’s critical to have data from a survey or “registry” to show your burden. With the Gorlin Syndrome Alliance, we used to say, “Basal cells are a huge burden.” From our global survey that I mentioned earlier, we now have the numbers, the data. So, do surveys to show the data, the burden, and the unmet need. It’s also the language of the FDA. They need to see the numbers. It can’t be subjective. It has to be objective: “I’ve had X number of basal cells on my face in the last 24 months. I’ve had Y number of basal cells on my trunk and legs,” etc. For pharma: use your resources. It’s silly to not do that, because you’ve got groups of people who are hungry for better treatments, and who can provide you with so much.

For more information on Patients as Partners, visit patientsaspartnersconference.com.