Unicycive Therapeutics' Framework For Speedier Clinical Trials
By Guru Reddy, Ph.D., vice president of R&D, Unicycive Therapeutics
The question our team gets asked most often is a simple one: How did you complete that clinical study so fast? The honest answer is that it started with a setback.
In 2023, just as we were preparing the NDA for our investigational oral phosphate binder for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis, the FDA requested additional clinical data. The drug is being developed under the 505(b)(2) regulatory pathway, which typically streamlines the path to approval. But an unexpected request for new clinical evidence at that stage caused a significant setback. Every month of delay led to lost revenue and, more importantly, lost time for patients who were waiting for better treatment options.
We had to act fast in response. Over the course of 12 months – the quickest we’d ever conducted a study – we evaluated the tolerability of our treatment at clinically effective doses. Of 128 patients screened, 86 patients were treated with oxylanthanum carbonate. Seventy-eight patients entered the maintenance period, of which 71 patients achieved adequate phosphate control. Ninety-one percent of patients achieved the target serum phosphate level of ≤5.5 mg/dL by the end of titration, compared to just 60% at screening, and the drug was well tolerated with a discontinuation rate of only 6%.
How did we do it? By foregoing traditional methods, rethinking the way we designed the study, sharpening our operations, and ensuring we had the right team doing the work.
Rethinking Study Design
Our starting point was alignment. Before we could design the right study, we had to fully understand what the FDA was asking us to do and why. There are always multiple ways to approach a clinical question. The goal is to find the path that is most direct, most efficient, and most likely to generate the data regulators actually need. For us, that meant being disciplined about three things in particular: eligibility criteria, study assessments, and sample size.
With eligibility criteria, there is a natural tendency to cast a wide net. However, long lists of criteria can slow enrollment. Our first step was to ask honestly: Who is the right patient population to answer this specific question?
The same discipline applies to assessments. Walk through any clinical trial protocol and ask why a given assessment is there. More often than not, the answer is some version of “That’s how we’ve always done it.” Over time, these habits get mistaken for scientific thoroughness, without anyone stopping to ask whether it still makes sense in a new context. Take physical examinations. Our initial protocol included them at every study visit, but after discussing with key leaders in nephrology, it became clear this assessment was entirely unnecessary for what we were measuring. It was ultimately removed, saving time without compromising data.
When we are not testing a specific hypothesis, it’s also critical to ensure the correct sample size to answer the question at hand. Including too many patients takes time you may not have; including too few patients may not help you answer the question. Because this was a single-arm, descriptive tolerability study and not a comparative trial, we planned to enroll approximately 90 patients to ensure at least 60 completed the maintenance phase, enough to draw meaningful conclusions without overextending our timeline.
The principle I have found most useful in keeping programs on track is to have a clear picture, from the very beginning, of what you want the prescribing label to say and to work backward from it. If every study and every data point is evaluated against that end goal, the unnecessary becomes much easier to identify.
Operational Excellence
Good study design is the foundation. Operational excellence ensures your design holds up under scrutiny. One of the most important operational decisions we made was to engage key opinion leaders (KOLs) early in protocol development. KOLs who work in the relevant clinical environment every day can look at a protocol with fresh clinical eyes and determine whether your design will work in practice. The value here is catching the blind spots that accumulate when a team is too close to its own work. Timing and framing matter, too. KOLs brought in too late tend to reopen decisions that should already be settled. Engaged at the right moment, with a focused question, they sharpen what you already have rather than complicate it.
Another major operational decision for our team was to conduct the study entirely in-house, without a CRO. We felt confident in our operations team’s ability to conduct clinical trials based on previous experience and knew the sites and principal investigators conducting the study were highly knowledgeable about CKD. By identifying data management vendors overseas, we also were able to jump-start the study much more efficiently and ensure our work was in constant motion. These choices allowed us to maintain direct oversight of the work at every stage.
The People Behind The Speed
None of this works without the right people. The team that executed this study was small, but it was built with deep multidisciplinary experience and, critically, a can-do attitude. With a leaner team and fewer layers of approval, we could identify issues, convene the right people, and make the right decisions.
In larger organizations, there is always another assessment to capture, another analysis someone wants to run, and with more functions and more people, a natural tendency for everyone to want to contribute. This can result in protocols that are comprehensive but answer questions that are not required, while slowing down the path to the ones that matter.
A team – often, it’s the small ones – with a clear mandate does not have that problem. In cross-functional teams where individuals carry knowledge across multiple areas, people understand the full picture and can align quickly. Still, this can carry real risk if left unchecked. Knowing a little about everything is not the same as expertise in everything. The teams I have seen make the best decisions are honest about that distinction, moving fast where their knowledge is sufficient and knowing precisely when to bring in someone who works in that specific area every day. Pharmacokinetic modeling and statistical analysis are two clear examples of this, each discipline sophisticated enough that we consistently engage external specialists, regardless of our team’s familiarity. That balance helps us to be even more effective.
What Cannot Be Compromised
Moving fast without discipline is not agility. There must be clear distinctions between eliminating unnecessary work and compromising the work that matters. The nonnegotiable here is data quality and integrity. Questions you do not need answered can be cut. But the quality of the data you do collect is not a variable.
Ultimately, high-quality data is necessary to develop new therapies. The patients waiting for new therapies are not waiting for us to check all the boxes we have in the past. Our obligation is to move efficiently, without sacrificing the rigor that makes our science trustworthy.
In this way, agility, properly understood, is not a small company advantage but one that belongs to any team willing to ask the right questions.
About The Author:
Guru Reddy, Ph.D., joined Unicycive in 2022 as vice president of preclinical R&D. Dr. Reddy has more than 25 years of R&D experience in the biopharmaceutical industry. Prior to joining Unicycive, he worked at Spectrum Pharmaceuticals for 15 years, where he held R&D roles with increasing responsibilities serving most recently as the vice president of preclinical R&D. He was responsible for the preclinical development and clinical pharmacology of a large product pipeline culminating in multiple NDA submissions and full regulatory approval of four drugs from the FDA.
Dr. Reddy has a wide range of experience in drug development, including preclinical research & development, early clinical development, and regulatory strategy.
Dr. Reddy earned his Ph.D. in biochemistry from the University of Poona/National Chemical Laboratory in India and obtained his post-doctoral training at Yale University. He is an inventor on 17 granted U.S. patents and has co-authored over 50 peer-reviewed publications.