PARIS — Consistent with what is known about minoxidil pharmacokinetics, a controlled trial found that an investigational extended-release oral formulation of minoxidil provided more favorable hair regrowth in patients with androgenetic alopecia than either immediate-release oral or topical formulations.

“Comparative analysis demonstrated significant superiority for all metrics,” reported Jerry Shapiro, MD, professor of dermatology at New York University School of Medicine, New York City.

The rationale for an extended-release pill is that the active form of the drug requires sulfation, which occurs after it reaches the circulation. “A longer time to sulfate is what we want, so if we keep the drug in the blood longer, there is greater sulfation and more activity,” explained Shapiro, who also believes that this formulation, if approved, will lower risks.

Extended-Release Has Potential Advantages

By avoiding drug peaks and troughs, “we think that the extended-release [formulation] offers an opportunity to maintain drug levels above those needed for therapeutic effect but below those associated cardiac adverse events,” he said during a late-breaker presentation on September 19 at the European Academy of Dermatology and Venereology (EADV) 2025 Congress.

The extended-release formulation, still known by its developmental label, VDPHL01, was tested in a retrospective phase 2 trial in which Investigator Global Assessment (IGA) was the primary outcome. IGA ratings were made by blinded investigators.

“Board-certified dermatologists looked at before and after photos without knowing which was before or after and what treatment was used,” Shapiro said.

A total of 20 people received 8.5 mg VDPHL01 twice daily for 4 months at which point results were evaluated. In the control groups, 33 patients received 5 mg immediate-release oral minoxidil once daily and 34 patients received 1 mL of 5% topical minoxidil solution twice daily, but the treatment in these two groups was continued for 6 months before and after IGA evaluation.

Hair regrowth was graded with a 7-point IGA scale on the basis of six photos for each participant, drawn from three vertex views and three frontal views.

Differences in responses were “dramatic,” according to Shapiro. With a 2-point increase from baseline considered clinically meaningful, the improvement in the extended-release group for both vertex and frontal growth met at least this threshold.

While Shapiro characterized a 2-point gain as a moderate if clinically meaningful response, he reported that a smaller but substantial group of patients achieved very good hair regrowth by the end of 4 months.

Conversely, the group receiving immediate-release oral minoxidil for 6 months had, on average, only a 0.5-point improvement in frontal growth and even less than that in vertex growth. None met the threshold of a moderate response.

In the topical group, there was essentially no improvement, on average, in vertex growth and an improvement in frontal growth that was more modest than that seen with the immediate-release oral formulation, Shapiro reported.

“Mean IGA improvement with VDPHL01 showed that the average patient achieved at least a moderate response vs comparators where subjects do not even achieve slight improvement,” he said, noting that the better result was also shown in less time (4 vs 6 months).

There were no serious side effects in this study, Shapiro said. Although there are a variety of adverse events associated with minoxidil, the most significant concern is risk for cardiac adverse events.

“These are very rare events, but they are obviously something we need to avoid,” said Shapiro, noting that he had to manage such an event in a patient on immediate-release minoxidil in his own practice. With immediate-release minoxidil, the greatest period of risk comes with a spike in concentration within the first few hours.

With the 8.5-mg twice-daily extended-release formulation taken as directed, the risk of reaching a blood level with the potential to provoke a cardiac event is very low even while higher average blood levels ensure therapeutic activity, according to Shapiro.

“Safety is really important, so this could be an additional advantage for this formulation if approved,” Shapiro said.

Assuming efficacy and safety is confirmed in future trials, this drug is expected to meet a sizeable unmet need, according to Shapiro. Although minoxidil is one of the most commonly used therapies for hair loss in men and women, Shapiro cited surveys in which only a small minority reported they are satisfied with this therapy. He said more than half are looking for new treatment options.

Asked to comment on the results, Gary Goldenberg, MD, an assistant clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai in New York City, agreed.

“While many treatment options are currently available, new and improved therapeutics and treatment modalities are needed,” said Goldenberg, whose treatment of hair loss represents a substantial proportion of his practice. He was not involved with the trial.

In his experience, the demand is growing. “Hair loss continues to increase in incidence, with more and more men and women suffering from this condition,” he said.

Based on the phase 2 data, Shapiro expects development of the extended-release formulation to advance. Emphasizing that “this is something new,” he said, “we are all excited” about the potential for a better treatment option.

The study was funded by Veradermics. Shapiro reported having financial relationships with this company, as well as AbbVie, DS Laboratories, Eirion, Lilly, Pfizer, and Thirty Madison. Goldenberg reported having no potential conflicts of interest related to this work.