Matt dives into a specific healthcare topic to help those in the industry, and those outside of it, better understand the market drivers causing today’s healthcare challenges.

I've been watching the Aeovian Pharmaceuticals and TSC Alliance partnership unfold, and it's forcing me to rethink everything I thought I knew about how pharma companies work with patient advocacy groups.

83% of pharmaceutical and biotech companies don't engage patient advocacy groups until Phase 3 trials.

And when they do bring them in? It's mainly to recruit patients for their trial, not to actually develop the trial itself.

Aeovian did something different. They brought the TSC Alliance to the table during Phase 1 and Phase 2. Not as consultants. Not as awareness partners. As development partners.

Here's what happened when the TSC Alliance got involved early.

They developed a protocol that reduced burden on patients while tracking clinically meaningful endpoints. Instead of forcing children with refractory epilepsy to make multiple clinic visits, they opted for home visits with families.

The results? Adherence improved. Medication compliance went up. More patients enrolled.

This shouldn't be surprising. Pediatric decentralized clinical trials that included mobile visits achieved 96.3% enrollment efficiency compared to 90.1% without them. Seven out of 13 studies implementing decentralized methods reported success with retaining subjects.

Home healthcare visits eliminate the burden on families juggling school schedules, work responsibilities, and care for fragile children. No travel to study sites. No exposure risk at physical locations. Just better data and happier families.

If the outcomes are demonstrably better, why don't more sponsors do this?

Apathy.

Big pharma fears the unknown. They fear missing pre-designated timelines for clinical trial recruitment and completion that will impact the company's bottom line. So they stick with doing it the way they've always done it.

They use the same cookbook for their clinical trials. Same standard sites. Product after product. Patient input only becomes necessary at the end of their trials and development.

Aeovian was different because they were a scrappy biotech without well-established relationships in clinical development programs. They took a chance at listening to the patient population.

The TSC Alliance brought the patients. They brought the patient experience. And Aeovian listened.

They asked for input on developing a decentralized trial. They wanted to know where trial sites should be based on knowledge of the patient population. They cared about what the impact of the trial would look like for the patient.

Big pharma still hasn't recognized this value, no matter how many case studies exist. They don't want to take the risk, though there may be an immense reward.

The numbers back this up. Phase 3 trials face a 45% failure rate. Over 90% of prospective candidates fail to enroll in traditional Phase 3 trials. Poor patient recruitment and flawed study design represent major contributing factors.

Consider this your wake-up call.

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The TSC Alliance didn't just bring patients to the table. They brought scientific infrastructure.

In 2018, they partnered with Aeovian by co-funding research through the TSC Preclinical Consortium. AV078 became the first drug candidate developed using the Consortium as the preclinical efficacy engine throughout the lead development process.

The Consortium's rigorous and disease-relevant models allowed Aeovian to rapidly evaluate selectivity, CNS penetration, and efficacy. Following positive results in the first mouse study in 2018, Aeovian developed improved clinical candidates over the next three years.

When advocacy organizations have family history studies or patient registries, you're reducing the risk of the study.

There's immense value in these registries. The nonprofit must be paid fairly for this value. But it also eases access to patients who are part of the registry.

Real-world data gathered from patient-consented medical records platforms has been used by emerging biotech companies to bolster investigational new drug filings. In one case, the FDA removed an initial clinical hold on an IND based on these data.

After the preclinical work, the TSC Alliance Endowment Fund invested in Aeovian's Series B financing.

Most people celebrate this as "skin in the game." I don't.

When a nonprofit becomes a financial stakeholder, they have access to the patients.

Here's the catch-22: If another company comes along with a drug being developed in that space, will they block access to those patients because they're invested in the other company?

I've seen this play out. Two years ago, a similar partnership in ALS led to warehousing of patients. Financial entanglements created exclusivity that actually limited patient access to other potentially better therapies.

Yes, financial investment signals that the advocacy group believes in the biotech company. But the relationship becomes too tight. The mission gets complicated.

Patient advocacy organizations are increasingly acting as venture philanthropists. The Cystic Fibrosis Foundation and Juvenile Diabetes Research Foundation have established models investing in companies with treatments aimed at single diseases.

But biomedical venture philanthropy among rare disease patient organizations faces long-term sustainability issues and difficulties in selecting appropriate research investments.

Advocacy groups should be paid a fixed rate. Something similar to a CRO contract, or a multi-year contract for their expertise.

Treat them as essential infrastructure rather than investors or consultants.

They provide patient insights. Registry access. Trial design input. Preclinical validation. Physician network access. All without creating the exclusivity trap that comes with financial investment.

The value is real. Research emphasizes that effective patient advocacy engagement should occur during Phase 1/Phase 2 design stages. Early patient input can reshape protocol design, reduce participant burden, and improve retention rates.

Patient registries and natural history studies require long-term support for data management, collection, analysis, and interpretation. Limited financial, expert, and personnel resources create sustainability challenges.

A CRO-style contract solves this. It provides sustainable funding without the conflicts that come with equity stakes.

If this model proves successful with Aeovian and TSC Alliance, what needs to happen for it to become standard practice across rare disease development?

The Department of Justice could be the first mover if there's not some sort of industry standardization for contracts like this to look more like CRO contracts.

Or this could be led by PhRMA, BIO, or any other coalition group.

The rare disease market is expected to grow at a compounded annual growth rate of approximately 9% through 2033. The sector's potential is driven by significant unmet needs of underserved patient populations.

But half of all rare diseases don't have a dedicated foundation or research support group. That translates to close to 15 million patients in the US without dedicated team support.

Patient advocacy groups of varying sizes, budgets, and maturity levels report interest in research, but limited funding and lack of disease awareness create barriers.

The Aeovian-TSC Alliance partnership shows what's possible when you bring patient advocacy groups in early. When you listen. When you design trials around patient needs instead of institutional convenience.

Home visits work. Decentralized trials improve enrollment and retention. Patient registries de-risk development. Preclinical consortiums accelerate timelines.

But the financial investment model creates problems we need to address. Exclusivity traps. Mission conflicts. Patient warehousing.

The solution isn't complicated. Pay advocacy groups like the essential infrastructure they are. CRO-style contracts. Multi-year agreements. Fair compensation for registry access and expertise.

Big pharma won't adopt this on their own. Apathy and fear of the unknown are too strong. But scrappy biotechs can prove the model works.

And eventually, the data will be too compelling to ignore.

Or the regulators will force the issue.

Either way, the cookbook approach to clinical trials is running out of runway. The 45% Phase 3 failure rate and 90% enrollment failure rate make that clear.

The question isn't whether this model will become standard practice.

The question is how many more patients will suffer through poorly designed trials before it does.