Dipexium advancing EU approval strategy for Locilex
With its Phase 3 program underway in the U.S., Dipexium (NASDAQ:DPRX) has begun the regulatory process with the European Medicines Agency (EMA) for its Locilex topical treatment for diabetic foot infections (DFI).
“Our strategy is to seek approval for Locilex in Europe based solely on data from our U.S. clinical trials, without any need to conduct additional trials in Europe,” David Luci, president and CEO, says in an interview with BioTuesdays.com.
“We have high expectations that we will receive regulatory buy-in from the EMA to proceed, not only because of the European guidelines, but also because the EMA has approved other DFI treatments developed in the U.S. on the basis of data from U.S. only trials,” he adds.
Dipexium filed a letter of intent and briefing package with the EMA’s Committee for Human Medicinal Products on Jan. 9 and expects to have a meeting with the committee on or about Feb. 18 for initial regulatory guidance. The company will then have two weeks to resubmit its briefing package with the input received at that meeting.
“In April or May, we should have definitive guidance from EMA, including a decision on whether we can file for approval based on the data from our U.S. trials, if the trials are a success statistically,” he suggests.
The company is targeting a marketing authorization application in Europe under the centralized process in the first half of 2016.
Feltl analyst, Ben Haynor, says the design of Dipexium’s U.S. trials should be acceptable to European authorities, without the company having to conduct additional trials in Europe. “There’s nothing I can see in the guidelines and regulations for European approval that would stand in the way of accepting the way the studies are designed,” he adds.
Mr. Haynor also suggests that having the ability to kill superbugs makes it even more likely that European authorities would accept Dipexium’s U.S. data, “as the EMA guidelines allow for limited evidence of clinical safety and efficacy when evaluating a compound targeting multidrug-resistant organisms, provided the spectrum of activity and unmet addressable need are accounted for in the evaluation.”
He rates Dipexium a “strong buy” with a $21.75 price target. The stock closed at $11.01 on Friday.
Mr. Luci suggests that Locilex could be priced in Europe at around one-half of its potential price in the U.S. “There are probably 50% more mild DFI patients in Europe than the U.S., and we figure the European market of Locilex could be around three-quarters of the U.S. potential, although we would support these general parameters with market and pricing studies as we proceed with EU development,” he adds.
Last July, Dipexium began two randomized, placebo-controlled Phase 3 trials – DPX-305 and DPX-306 – in the U.S., and plans to enroll 180 patients with mild DFI per trial under a special protocol assessment from the FDA.
Patients are receiving 14 days of treatment, with a follow-up at day 28. The primary endpoint is whether infections are being resolved in the judgment of physicians using DFI treatment guidelines as an objective measure.
Mr. Luci says the company expects to report top-line data in the second half this year and file its amended NDA before the end of the year. It expects to receive a response from the FDA in the first half of 2016.
“In our studies, we’re seeing wound closure rates of over 50% in patients whose infections have been resolved, even though we don’t know, at this point, which patients are receiving Locilex or placebo, because the data we are able to observe are blinded,” Mr. Luci points out.
Wound closure, which is a secondary endpoint in Dipexium’s Phase 3 trials, is a $2-billion annual market. The only approved therapeutic is Regranex. While it is indicated to close wounds, it typically takes 90-to-120 days to achieve wound closure and is used only in patients with uninfected diabetic foot ulcers (DFU) at baseline. Furthermore, Regranex received a Black Box cancer warning from the FDA in 2008. Infected DFU patients cannot take Regranex.
“The fact that we are potentially closing wounds in infected patients, if it is in fact Locilex, in 14-to-28 days could make our product front-line therapy in DFU to close wounds as well as prevent infections and could potentially double the market for the product,” Mr. Luci contends.
Diabetics commonly develop DFU for many reasons, including by reason of a lack of sensation in their extremities. Some 61% of DFUs will become DFIs. However, before a wound can be treated, the infection must be removed.
The Infectious Diseases Society of America guidelines consider off-label use of oral antibiotics to be acceptable in the absence of an FDA-approved product for mild DFI. The annual worldwide market for DFI antibiotics is $1.46-billion, of which the U.S. market is just over $1-billion.
All classes of oral antibiotics are associated with a number of significant drawbacks, including systemic antibiotic resistance, limited spectra of activity, poor safety and tolerability, and drug-drug interactions with diabetes medications that can affect blood glucose levels in patients.
Last September, President Obama signed an executive order, appointing a task force to incentivize sponsors of new antibiotics to treat resistant bacteria. “We’re one of those companies,” Mr. Luci points out.
Antibiotic resistant infections annually sicken more than two million Americans, killing at least 23,000 people, according to the Center for Disease Control. No new type of antibiotic has been developed since the late 1980s. From 2001 to 2013, the FDA approved only three new molecular entities to combat bacterial diseases – the lowest rate since the 1940s. The pharmaceutical arsenal against bacterial infections has declined by 15% to 96 by the end of 2013 from 113 in 2000.
In product development, Dipexium plans to sponsor two animal studies this year on an IV formulation of Locilex that could lead to patent applications for a new chemical entity and a second “home grown” product in its pipeline. The first of these two animal studies began in January 2015 at the University of Wisconsin.
The IV formulation potentially would be used in the ER for severe DFI, inter-abdominal infections, urinary tract infections and GI infections. Mr. Luci says that by the end of 2015, the company may have a more clear direction to announce regarding the potential of its IV formulation and the clinical pathway forward.
“We’re holding three lottery tickets right now – the European strategy without any further trials, wound closure data in the ongoing Phase 3 blinded trials and an IV formulation – and if we cash any one of these lottery tickets this year, Wall Street should recognize the value added, which may result in substantial appreciation in our market cap,” Mr. Luci contends.