The recent earnings call for <a href="https://seekingalpha.com/symbol/TRVI" target="_blank" rel="noopener noreferrer">Trevi Therapeutics (NASDAQ: TRVI)</a> buzzed with the usual clinical trial updates and financial results. But hidden beneath the surface lies a potentially explosive catalyst: the potential for Trevi's lead drug, Haduvio, to remain unscheduled. This could open the door to a far larger market than previously anticipated.

Trevi is developing Haduvio, an extended-release formulation of nalbuphine, for the treatment of chronic cough in two debilitating conditions: Idiopathic Pulmonary Fibrosis (IPF) and Refractory Chronic Cough (RCC). While the efficacy of Haduvio in these conditions is undeniably exciting, the implications of its potential unscheduled status are truly groundbreaking.

Imagine a world where a highly effective cough treatment is readily available, unburdened by the restrictions and stigma associated with scheduled drugs. This isn't a utopian fantasy, but a real possibility for Trevi and Haduvio.

The company's recent <a href="https://seekingalpha.com/symbol/TRVI" target="_blank" rel="noopener noreferrer">earnings call</a> shed light on their strategic approach to achieving this goal. Their "eight-factor plan," developed with input from the FDA, is a comprehensive roadmap designed to demonstrate the low abuse potential of oral nalbuphine ER and secure its unscheduled status. This plan includes preclinical data, mechanistic rationale, clinical data from development programs, results of the ongoing Human Abuse Potential (HAP) study, and a compelling public health rationale.

The fact that parenteral nalbuphine has been unscheduled for years, coupled with the unscheduled nature of both components of nalbuphine's mechanism (kappa agonist and mu antagonist), creates a strong foundation for Trevi's argument.

Potential for 'Likability' Without Abuse Concerns

While analysts are rightfully focused on the HAP study results expected later this year, they seem to be overlooking a crucial detail. Trevi's CEO, Jennifer Good, subtly hinted at the potential for some level of "likability" for Haduvio even in the absence of scheduling concerns. She highlighted the FDA's focus on "dose response to likability," where increasing likability across escalating doses raises red flags.

This implies that a moderate level of likability, without a dose-dependent increase, might not be a deal breaker for the FDA. In other words, Haduvio could possess qualities that make it preferable to a placebo, without necessarily triggering concerns about abuse potential.

This nuanced distinction has significant implications for Trevi's market potential. If Haduvio demonstrates a favorable safety profile and a desirable level of "likability," it could capture a broader segment of the chronic cough market beyond those with the most severe symptoms.

A Billion-Dollar Opportunity in RCC?

The RCC market is estimated to affect up to 10% of the adult population. Within this market, 44% of patients fall into the moderate to high cough frequency category, while only 29% have very high cough frequency.

Current P2X3 inhibitors, like the one developed by Merck, have only shown efficacy in the very high cough frequency group, potentially limiting their market share to less than a third of the total RCC population. However, Haduvio, with its dual mechanism of action and strong efficacy across varying cough frequencies in the IPF trial, could potentially address close to three-fourths of the RCC market.

To put this in perspective, let's assume a conservative market penetration of 20% and a treatment cost of $5,000 per year (in line with other specialty drugs). If Haduvio secures unscheduled status and captures 75% of the RCC market, this translates to a potential annual revenue of:

<strong>0.10 (adult population) x 0.75 (market share) x 0.20 (market penetration) x $5,000 (treatment cost) = $750 per adult</strong>

Considering the U.S. adult population exceeds 250 million, this equates to a staggering <strong>$187.5 billion</strong> market opportunity. Even capturing a fraction of this market would make Trevi a major player in the chronic cough space.

Conclusion

The potential for Haduvio to become the first unscheduled, highly effective treatment for chronic cough is a game changer. While the HAP study results will undoubtedly be a key inflection point, investors should pay close attention to the nuance in Trevi's messaging and the potential for Haduvio to unlock a billion-dollar opportunity by addressing a far broader market than currently anticipated.

"Fun Fact: Did you know that chronic cough can be so severe that it can lead to rib fractures, urinary incontinence, and even fainting? Trevi's work on Haduvio provides hope for patients suffering from this often-overlooked condition."