By Len Zehr
Juniper Pharmaceuticals (NASDAQ:JNP) expects to report results in the third quarter from a Phase 2b clinical trial of its 10% lidocaine bioadhesive vaginal gel, COL-1077, a local anesthetic for pain from minimally invasive outpatient gynecological procedures.
“There is no product like it on the market,” Frank Condella, president and CEO, says in an interview with BioTuesdays.com, referring to the lidocaine bioadhesive vaginal gel, which a woman self-administers at home prior to a procedure at her physician’s office.
“Because a patient arrives at a physician’s office procedure-ready, this has the potential to become the standard of care where none exists,” he adds.
Mr. Condella explains that Juniper’s bioadhesive delivery system (BDS) is a proprietary polycarbophil gel that adheres to vaginal epithelial tissue for controlled and sustained release of drug over time until the BDS formulation is discharged during normal cell turnover. This occurs every three-to-five days for the vaginal epithelium.
He points out that vaginal delivery has the benefit of absorption into local tissue and avoids first-pass metabolism in the liver. In addition, lower plasma levels improve drug safety profiles and avoid potential gastrointestinal side effects.
Juniper has already brought three products to market using its BDS technology: Replens, RepHresh and CRINONE progesterone vaginal gel. CRINONE is Juniper’s most successful product to date and its single largest revenue source. It is marketed by Allergan in the U.S. and by Merck KGaA in over 90 countries worldwide.
Mr. Condella says Juniper transformed 18 months ago to focus on drug development, using revenue from its core operations, including CRINONE and its wholly-owned subsidiary, Juniper Pharma Services, a British pharmaceutical development, clinical trials manufacturing and services consultancy business.
Juniper’s BDS proprietary polycarbophil gel adheres to vaginal epithelial tissue for controlled and sustained release of drug over time until the BDS formulation is discharged during normal cell turnover
“We aim to leverage the time- and cost-effective U.S. 505(b)(2) regulatory pathway with new formulations of existing pharmaceuticals,” he adds.
Mr. Condella, who announced in June his plan to retire later this year, says the ongoing Phase 2b clinical trial is nearly fully enrolled with 185 women at 25 clinical sites in the U.S. The study is evaluating the efficacy and safety of a self-administered single dose of COL-1077 in women undergoing pipelle-directed endometrial biopsy with tenaculum placement.
The primary endpoint is pain reduction at the time of biopsy. Secondary endpoints include reduction in pain intensity at additional time points and patient-related outcomes.
Assuming positive outcomes of the trial, Juniper expects to initiate a Phase 3 trial in early 2017. The ongoing trial could qualify as one of two pivotal studies for regulatory approval if it meets its primary endpoint.
Subject to FDA marketing approval, Juniper expects to independently commercialize COL-1077 in the U.S. and is pursuing partnerships for development and commercialization outside of the U.S.
George Elston, CFO, says pain from minimally invasive gynecological procedures represents an attractive market opportunity, with more than seven million in office procedures performed each year in the U.S. “With no current approved standard of care, our 10% lidocaine bioadhesive vaginal gel is well positioned to be a market leader in pain control for women undergoing these procedures.”
While there are other lidocaine sprays and gels that work on surface tissue, he says these don’t provide sufficient time for the analgesic to penetrate deeper tissue where the procedure takes place. “But lidocaine with our bioadhesive gel adheres to the vaginal epithelium, enabling drug delivery over the course of many hours, which is the key differentiator,” he adds.
Juniper also has acquired a first-in-class intravaginal ring (IVR) technology, developed in the laboratories of Dr. Robert Langer at MIT and Dr. William Crowley of the Massachusetts General Hospital, which could revolutionize delivery of single- and multiple-drug therapeutics in women.
Mr. Elston explains that unlike reservoir and sandwich type rings on the market, which can only deliver small molecule drugs, Juniper’s IVR is differentiated by having drug homogenized in an ethylene vinyl acetate polymer matrix, without the need of a membrane or reservoir to contain a drug, or control its release.
“Through this inherent design, our IVR has the potential to deliver a range of poorly bioavailable drugs, with small or large molecular weights, as well as multiple drugs at multiple release rates, and multiple dosages, from a single ring,” Mr. Condella contends.
Juniper’s IVR technology conceptually allows sustained delivery over time – from weeks to months. In addition, the vaginal ring can hold one to two orders of magnitude more drug than transdermal patches, greatly expanding the number and types of drugs that can be delivered, and extending the duration of use from a single dose.
The company is currently developing three IVR product candidates, including JNP-0101, an oxybutynin IVR for the treatment of overactive bladder in women; JNP-0201, a combination IVR with natural progesterone and estradiol segments to address the symptoms of menopause; and JNP-0301, a natural progesterone IVR to prevent preterm birth.
Earlier this year, the peer-reviewed Journal of Controlled Release published a human proof-of-concept study demonstrating the successful delivery of a nine-amino acid peptide, leuprolide, using the company’s IVR technology. Leuprolide is sold commercially as an injectable under the brand names Eligard and Lupron for the treatment of precocious puberty, prostate cancer, infertility, fibroids, and endometriosis.
COL-1077 is a local anesthetic for pain from minimally invasive outpatient gynecological procedures.
Juniper’s lead IVR indication is overactive bladder (OAB) in women, a $1.3-billion market in the U.S. in 2014. OAB, which is characterized by a compelling need to pass urine, affects some 20 million women in the U.S., of which nine million are being treated.
The most common prescription for OAB is generic oxybutynin. However, 70% of OAB patients discontinue oxybutynin within the first year because of perceived ineffectiveness and side effects.
JNP-0101 has been designed to address the most pressing unmet needs in OAB, including reduced side effects that result from first pass hepatic metabolism and sustained delivery. The once-monthly IVR is likely to increase patient convenience and compliance as well as improve disease management and overall health outcomes.
The company held a pre-IND meeting with the FDA to confirm its 505(b)(2) regulatory pathway and is conducting an animal pharmacokinetic study to obtain an appropriate dose of JNP-0101 in the ring. Juniper Pharma Services has begun manufacturing the IVR.
Juniper plans to file an IND for JNP-0101 later this year and move into a Phase 2 bioavailability and dose-finding study in 2017.
Juniper’s next IVR candidate is JNP-0201, a progesterone plus estradiol two-segment ring, for extended delivery hormone replacement therapy (HRT). There are some 45 million U.S. women approaching or in menopause.
Mr. Condella says the $2.2-billion U.S. HRT market is largely serviced by compounding pharmacies for women seeking natural products as an alternative to synthetic estrogen. There are no FDA-approved combination products that deliver natural hormones like JNP-0201 and “we see a real market opportunity for our combination ring,” he adds.
The company is currently conducting drug loading and release profile studies and hopes to move into Phase 1 testing in 2017.
Juniper’s Intravaginal Ring is differentiated by having drug homogenized in an ethylene vinyl acetate polymer matrix, without the need of a membrane or reservoir to contain a drug, or control its release.
Also in preclinical development is JNP-0301, a progesterone IVR for the prevention of preterm birth. The U.S. preterm birth rate rose to 9.6% in 2015, the first increase in the past five years. The single most important predictor of risk for preterm birth is a short cervical length of 3.0 cm or less at mid-pregnancy, Mr. Condella points out.
There are no FDA-approved products for the prevention of preterm birth in women with short cervical length, “even though there is a clear medical consensus that vaginal progesterone should be administered when short cervical length is detected at mid-pregnancy,” he adds. “Since there is nothing to run a study against, the issue is how do you conduct a placebo-controlled clinical trial?”
The company has a study underway to determine current U.S. practice for the diagnosis of short cervical length and subsequent use of vaginal progesterone. Results of the study will be discussed with the FDA later this year to determine a clinical and regulatory path for vaginal progesterone to reduce the risk of preterm birth in women with a short cervical length.
“With COL-1077, JNP-0101 and JNP-0201, we have the potential for three new product launches within five years,” Mr. Condella suggests. “JNP-0301 is still a wildcard for us.”
In addition to new products, Mr. Elston says Juniper has started a robust business development initiative this year for additional value creation.
“We are looking to partner with other companies, using our IVR technology to create new products, either as part of a lifecycle management program, or to leverage the benefits of local delivery to achieve systemic activity with reduced side effects.”
He lists breast and ovarian cancers, osteoporosis, multiple sclerosis, rheumatoid arthritis, and pulmonary arterial hypertension as potential target opportunities for partnering Juniper’s IVR technology.
“We’re working on a list of products for potential partnering and, with our UK unit for prototype development, we hope to have some interesting news flow in 2017,” he suggests.
