Managing Critical Risks in Early-Stage Medtech

Key Learnings From Amar’s Experience

• Understanding and mitigating risks early on is essential. Don't take on too many risk factors simultaneously, especially those outside your expertise. Choose ideas with immediate, clear value propositions over those with long-term, cloudy outcomes. Creating a "wow moment" with demonstrable results will likely result in market pull vs. market push.
• When designing clinical trials, ensure your primary endpoints align clearly with the core function of your technology. You can have cascading secondary endpoints, but you must start simple and layer in sophistication only after your key goals are established.
• Pick your initial indication wisely. A strong start can set the stage for future success, while a misstep can hinder your platform's potential. Identify areas where there's a real, pressing need and a hungry market. Aim for something that has the potential to be disruptive, instead of implementing minor tweaks to existing solutions.

Amar Sawhney is a chemical engineer with deep experience in absorbable and biocompatible materials, from sealing leaks in organs to delivering targeted drugs. “These materials are used in various surgical areas, and we form companies around them to execute upon each of those business plans,” says Amar. Today, he’s the CEO of Instylla, Rejoni, Sealonix, and Pramand. 

One of Amar's most significant innovations is the process of in-situ polymerization, which changes materials from liquid to solids, setting off chemical reactions in contact with living tissue inside the body and creating flexible seals on organs that may be leaking air, blood, or cerebrospinal fluid. This breakthrough enables a variety of biosurgery applications. Additionally, his work with hydrogels, which absorb liquids at different rates, is equally noteworthy, setting the foundation for many biosurgery applications and drug delivery systems. 

Currently, at Instylla, Amar is developing liquid embolics with initial clinical applications in interventional oncology and peripheral hemostasis. Prevailing embolization technologies include beads, particles, solvent-based liquid glues, coils, and plugs. However, Amar highlights that none of these are based on aqueous, self-polymerizing, and absorbable materials. Instylla’s aqueous and absorbable liquid embolic, Embrace, mixes with blood and self-polymerizes without the need for blood clotting. Unlike other embolics that use permanent metal particles or plastic resins, “over six months of duration, the materials are designed to absorb and leave nothing behind,” explains Amar. 

Embrace’s regulatory pathway has been as demanding as its development. Subject to a PMA process, it must meet rigorous safety and efficacy standards compared to a 510(k). Having undertaken a trial on its efficacy in hypervascular tumors on 150 patients—the largest trial of its kind—the team is in the home stretch. If they can show that these tumors can be safely killed by shutting down the blood supply through embolization, Embrace will be off the races soon.

Picking the Right Battles

Amar has worked on many early-stage companies from their inception, so he knows quite a bit about starting off with limited capital. His guiding principle for the product development phase is understanding risks and uncertainties. He identifies six major areas when evaluating whether a medtech idea has legs: 

1. Market understanding: A large, well defined market.
2. Technology validation: An impactful technology that is differentiated and can make a significant change.
3. Team capability: A go-getter team—in Amar’s words, “not just a bunch of academics stumbling through the processes.”
4. Financing: Capital to make it happen.
5. Clinical and regulatory pathway: A roadmap for your particular clinical pathway and funding to sustain it.
6. Reimbursement environment: Who will cover the cost? Insurance, government programs, or self-pay? Is there an existing reimbursement pathway? Do you need a new billing code? Does your product fit within an existing DRG? 

Amar adds, “Sometimes you have to almost start from the sixth one first.” 

Obviously, tackling too many risks simultaneously lowers the probability of success. “If you were to apply 50% probability to the success of each one of these items, tackling more than three, you only get a 12%,” Amar explains. You must target projects with immediate, clear value propositions without unnecessarily high risk exposure. 

What makes a value proposition clear and immediate? Consider a sealant for a cerebral spinal fluid leak. You can see the leak stop right away. This makes the value proposition clear and immediate. On the other hand, it’s hard to see immediate results with, say, a drug for Alzheimer's disease, as improvements in memory are subtle and can be influenced by natural aging. It can take years to determine if the drug is effective. Although the size of the market for Alzheimer's disease can justify the investment, if the market opportunities are similar, the wise choice to make, for the sake of example, is the sealant, according to Amar. 

Amar also underlines that products addressing acute, unmet needs are more likely to succeed as the market will “pull” them or actively seek them out. You should aim to create a "wow moment" in practical settings and make the immediate impact of the product evident and impressive. As a startup that naturally lacks the marketing muscle of large companies, you must rely on strong market pull. If you follow Amar’s advice and focus on desperate and obvious needs, you land in an audience that actively seeks your product rather than needing to be convinced to adopt it.

Logical Clinical Study Design

Amar’s approach to designing clinical studies has evolved significantly over the last 20 years. In the past, separate pilot and pivotal studies were the norm for him, often adding significant time to the development process. Now, he prefers adaptive studies that incorporate a pilot phase within the larger study. This allows for early data submission and feedback from FDA, resulting in faster progression into subsequent phases. “For some of my new companies, we do a pilot study on 10, 15 patients, report back to FDA, and we negotiate the overall protocol for the remaining patients.” 

When setting up a trial, Amar emphasizes that the primary endpoints should closely align with the device’s main function. For instance, when developing an embolic, the primary endpoint should be something that directly reflects the device's purpose, i.e., cessation of blood flow. Endpoints that are further away from the device’s primary action, such as tumor regression, introduce more variables and noise, and in turn, reduce the likelihood of success. 

Now, this doesn’t mean you can’t have cascading secondary endpoints. But you need to start with directly achievable goals and progressively move to more complex ones. It’s important to ensure that your primary and secondary endpoints are logically structured in a stepwise fashion. 

The other thing that has changed over Amar’s 20 years in the industry is the landscape for conducting global trials. Europe was once a favored location for initial studies thanks to its regulations. But the recent MDR changes have altered things significantly. Amar now considers locations like Australia, New Zealand, Kenya, and Mexico, depending on the study’s specific needs and regulatory frameworks. Amar says, “You can get into first-in-man sooner in those other geographies.” Still, it's crucial to choose locations known for sound science and credible data when submitting to the FDA. “If you go and do it from some less established, less rigorous country, then the data may not be as believable,” he explains. Understanding each country’s regulatory advantages and challenges is critical to ensuring that the trial data is both credible and acceptable. 

Trial success heavily relies on finding motivated clinicians who can effectively handle the device and are committed to the study. This is especially important in international settings, where challenges in logistics and communication can arise. A dedicated and capable investigator can make a significant difference in the outcome of the study.

Initial Indication Paves the Path

When you have a platform technology, picking the suitable initial indication to pursue, is critical. “If you have a platform and you pick the wrong place to start, your platform will be thrown out; the baby will be thrown out with the bathwater. Nobody wants to revisit it if you fail,” he explains. 

When choosing an indication, Amar’s advice is to focus on areas with significant need and existing market demand. For example, Instylla’s first indication is to address hypervascular tumors. Amar saw a clear market need and the potential for substantial improvement over existing treatments. “People are willing to spend a lot of money on treating tumors, and there's already a fair amount of products being sold right there,” he notes. 

Amar also warns against relying on incremental improvements, as they are often insufficient to change entrenched behaviors. A product that offers only slight improvements over existing solutions may struggle to gain adoption due to the effort required to change established practices. Instead, Amar advises aiming for significant advancements that clearly demonstrate superior outcomes. 

Lastly, aiming for a truly compelling result is crucial for gaining traction in a competitive landscape. “When a doctor uses your technology, they should see immediate, impressive results and say ‘I’ve been cutting steak with a butter knife all my life, and you suddenly hand me a Ginsu knife’, that’s what you’re looking for,” Amar explains. Such an impact can capture the attention of practitioners and stakeholders and open the way to widespread adoption.