Working (Successfully) With Pharma: A PAG's Perspective

A conversation with TSC Alliance President and CEO Kari Rosbeck

Conversations about partnerships in clinical research typically revolve around the sponsor, the CRO, and the sites. These three key players are the most commonly discussed, but a crucial fourth exists: the patient advocacy group (PAG).

And if it were up to Kari Rosbeck at the TSC Alliance, early partnerships with pharma would be routine in the drug development process. Yet, she and others must still steal every opportunity to remind sponsors of their value.

No reminders are needed for Aeovian Pharmaceuticals, which knows well the benefits of working early and often with a patient advocacy group. It joined forces with the TSC Alliance years ago, early in development, to test an early-stage, first-in-class selective mTORC1 inhibitor for TSC-related refractory epilepsy.

Today, that relationship continues and has even evolved to include an investment toward the $55 million in Series B funding, which comes from the advocacy group’s endowment fund.

In this interview, we hear from Kari about the partnership – how it happened, what it’s yielded, and why others should follow suit.

(For Aeovian’s perspective, see the complementary interview with its CEO Allison Hulme, Ph.D.)

Clinical Leader: What is the TSC Alliance, and how were you introduced to Aeovian?

Kari Rosbeck: The TSC Alliance is a nonprofit that focuses on those living with tuberous sclerosis complex, by catalyzing new treatments, driving research toward a cure, and expanding lifelong access and support. Tuberous sclerosis complex (TSC) is a rare genetic disorder that causes generally non-malignant tumors to grow throughout the body. It is the leading genetic cause of epilepsy and one of the leading genetic causes of autism.

We have been funding research since 1984. We initially awarded research  grants.  In 2006 we launched  a natural history database tied to a biosample repository we initiated in 2014 and more recently launched a clinical research network. In 2016 we started a preclinical consortium with goal to collaborate with both industry and academia. And this is where Aeovian comes in. So, we've spent the past 20 years building these research resources to accelerate drug development in TSC.

We started working with Aeovian soon after we launched our preclinical consortium. We've had some long-standing members including Jazz Pharmaceuticals,  one of our first industry members, and UCB.

But Aeovian was really one of the first smaller biotechs. We tested Aeovian’s first drug in our preclinical consortium as a co-development project. We paid for part of that first investigation on a promissory note, which they paid back. That really led to their early funding as an organization because of the positive results that came out of that first experiment in our preclinical consortium. Over the next three years, we worked together through our preclinical consortium to help develop the first clinical candidate that's come out of the consortium to go into clinical trials.

What are all of the ways in which the Consortium imparts either patient insights or scientific input to partners such as Aeovian?

Members of the TSC community serve on the preclinical consortium steering committee and offer insights on what’s important to them and others living with TSC  We have working groups – for epilepsy, tumor growth, and behavior, and we bring in mouse models that best reproduce the human condition. We now we  five in epilepsy and a couple of tumor models.

Our steering committee focuses on helping to accelerate potential compounds. We have annual meetings of the steering committee where we'll look at nominations — still screening on behalf of academic researchers with donor dollars — but also focus on industry and providing them a platform to easily test and screen compounds. There's usually one company that also sits on the steering committee because they can represent that industry voice and what will be helpful to industry to quickly accelerate new treatments.

How did TSC Alliance go beyond awareness, fundraising, and outreach to provide both preclinical and clinical support?

In 2011, we hired a new chief scientific officer, Steve Roberds, who came out of industry with the very purposeful aim of accelerating new treatments. At that point, we'd been working with Novartis and had our first approved drug. Everolimus  shrinks tumors in the brain and kidneys and is adjunctive therapy for seizures associated with TSC, but it's not curative.

So, we really wanted to continue to move new compounds through the pipeline. Steve came out of the drug discovery arm of Pfizer, where he took compounds that sat on the shelf to help move them to new potential therapies, working with academic researchers. And then in 2015, we co-hosted a strategic research conference with NIH, funded out of the National Institute of Neurological Disorders and Stroke (NINDS), and with the TSC Research Program at the Department of Defense.  The Conference included  the nine different institutes at NIH that work in TSC, academic researchers and industry representatives.

The outcome was a research strategic plan. And two of the recommendations that came out of that plan were assigned to the TSC Alliance - developing a preclinical consortium and starting a biosample repository. Those were some of the biggest needs from academia and industry to really accelerate progress. 

In 2019, under  Steve's leadership, we wrote a research business plan to help build and sustain the research resources I mentioned earlier that make up our research platform.

Through the years, we had interviewed lots of other organizations who have built similar models — Cystic Fibrosis Foundation, Juvenile Diabetes Research Foundation, and then Faster Cures through the Milken Institute developed a blueprint disease research organizations could follow. We really were very thoughtful about adding the pieces over time in order to sustain the program.

For our pharma and biotech readers, how can they reach out to patient advocacy groups to support and work with them?

It starts way before you get to the clinical testing of compounds. Also, just because an organization represents a disease that is rare or ultra rare doesn't mean they don't have resources. We have had 27 industry partners, have tested 97 compounds, and have 12 clinical candidates now.

Always check in with the patient advocacy organization; you might have no idea what tools are important or if you are really addressing an unmet need. Even having advocacy conversations or advisory boards with communities early on is important.

If you just want it to be a rubber stamp, that's too late to start the conversation.

Have you had experiences where companies have done just that -- reached out to you when they are ready to start trials and just want you to give it a once over? What do you tell them?

Yes. If you're at the 11th hour, we're not just going to rubber-stamp things. We're going to tell you exactly how this is going to impact the community. We offer a realistic viewpoint of what is likely to be successful or unsuccessful with our community.

Why do you think some sponsor companies don’t reach out early?

I think the field is changing, and I want to compliment the industry partners we have been working with. I think for a long time industry thought that clinicians were their only key opinion leaders. But there are always things that families may think of because they're living this experience.

In our early clinical trials, we had families who took a second mortgage on their home just so they could participate in clinical studies. And those were industry studies. It is a sacrifice for families. It's so important to hear what's going to be meaningful and realistic for them.

What does your partnership with Aeovian look like now and in the future as they try to achieve clinical milestones?

We educate our community about any clinical trial that's happening. We will invite Aeovian to come present, probably with a PI, to our community. They want to know: What's the scientific background of this particular compound, and what is an mTORC1 selective inhibitor? Education is really the key. We provide the tools for our community to weigh the risk and benefit. That is a family's decision, but we feel it's our role as a patient advocacy group to educate the community on everything they need to know about that particular trial.

About The Expert:

Kari Luther Rosbeck has served as president and CEO since November 2007 and has proudly served the TSC community for 24 years. During her tenure, the TSC Alliance established a comprehensive research platform fostering collaboration with industry and academia to move treatments for TSC forward in a more expedited way. Because of her leadership, the organization has taken an active role in educating the TSC community about clinical trials to diminish the time for recruitment, including pivotal trials that have led to three FDA-approved drugs specifically for TSC. In 2019, the organization launched a research business plan, paired with an aggressive fundraising campaign, leading to more than $23 million raised. Kari has made it her life mission to use her 35 years of nonprofit and volunteer management experience to help create a future where everyone with TSC has what they need to live their fullest lives.