With a PDUFA date of June 28 for an FDA decision on its oral testosterone replacement therapy (TRT) product candidate, TLANDO, Lipocine’s (NASDAQ:LPCN) next two pipeline product candidates are advancing towards Phase 3 ready status this year.
“We have a robust pipeline with a number of key milestones in 2016 besides the decision on TLANDO,” Morgan Brown, EVP and CFO, says in an interview with BioTuesdays.com.
Mr. Brown points out that Lipocine has requested an end-of-Phase 2 meeting with the FDA about its oral alternative for the prevention of preterm birth, LPCN 1107, and expects the meeting to take place in the third quarter. Mr. Brown also expects to report top-line, Phase 2b study results for a second generation, once-daily, oral TRT drug candidate, LPCN 1111, in the third quarter this year.
The company anticipates an end-of-Phase 2 meeting with the FDA about LPCN 1111 in the second half this year.
Mr. Brown says that TLANDO, which is a twice-daily product, has the potential to be the first approved oral option for TRT, a $2-billion-a-year market in the U.S. that now consists of topical gels and injectables.
“We are targeting the same label as competing products but have a potential game changer with the convenience and safety of an oral treatment,” he adds.
Low testosterone, or male hypogonadism, often results from insufficient secretion of testosterone, a hormone responsible for the normal growth and development of male sex organs and for the maintenance of secondary sex characteristics.
Hypogonadism affects up to 20 million men in the U.S., of which 2.2 million men are currently being treated, including 700,000 new patients to treatment each year. Prescriptions for TRTs have remained stable at around 500,000 a month over the past year, about evenly split between topical gels and injectables, despite additional cautionary label guidance from the FDA in early 2015.
Mr. Brown explains that Lipocine does not develop new chemical entities but enhances existing molecules with the company’s proprietary delivery technology, known as Lip’ral, which is based on lipid compositions that disperse in the gastrointestinal tract for improved absorption of an insoluble drug.
As a result, he says TLANDO’s active molecule, testosterone undecanoate, by-passes the liver in the first pass of metabolism and can maintain effective testosterone levels for 10-to-12 hours from a single dose. “TLANDO has demonstrated consistent and predictable performance in clinical studies,” he adds.
On the other hand, native testosterone has poor oral bioavailability, with a very short half-life of about 30 minutes because of metabolism in the liver. As a result, he points out that impractical daily doses would be required to obtain effective levels of testosterone.
In pivotal studies, TLANDO restored 87% of subjects to a normal testosterone range. Testosterone levels were not sensitive to the fat content in food, although a minimum of 15 grams of fat are required to stimulate lymphatic flow, and remained consistent in the morning and evening. Secondary endpoints generally were consistent with approved products. In addition, the company’s 52-week exposure data demonstrated that TLANDO did not induce cardiac, hepatic or drug-related serious adverse events.
The FDA accepted Lipocine’s NDA for TLANDO last October. The FDA assigned a PDUFA date of June 28, without holding an advisory committee meeting, which “we view as a very positive sign,” Landenburg Thalmann analyst, Matthew Kaplan, said in a recent report.
He rates Lipocine a “buy” with a $20 price target. The stock closed at $9.07 on Friday.
Mr. Brown contends that TLANDO differentiates itself from the market leader, Androgel 1.62%, by not being prone to accidental testosterone transference to women and children. Androgel 1.62% had sales of approximately $750-million in 2015, even with a black box warning about transference from the FDA.
“Besides being a preferred oral option, TLANDO’s starting dose is the correct dose for most patients,” he adds, “and, as a result, requires fewer doctor visits.”
Certain testosterone injectables carry a black box warning from the FDA about potential pulmonary embolisms and episodes of anaphylaxis. In addition, pain from injection, injection site reactions, and needle phobia and fatigue are potential drawbacks of injectable and implant TRTs.
As a result, Mr. Brown points out that the median persistency on branded TRT products is about 100 days, which is unusual for a chronic therapy. “Obviously, creams and gels can be messy and you have to wait 10-to-20 minutes before getting dressed.”
The company also plans to seek regulatory approval for TLANDO in Canada in the second half this year.
Regarding a commercial plan for TLANDO, Mr. Brown says the company is having active discussions with multiple potential partners who have a primary care sales force. About 65% of prescriptions for TRTs are written by primary care physicians.
“In parallel with those discussions, we’re also considering building our own sales force to target high prescribing urologists and endocrinologists, as well as high prescribing primary care physicians,” he adds.
“We’ve hired a core commercial team and established an office in New Jersey and we’re making preparations in terms of messaging, market research and territorial alignment in case we go ahead with some form of sales and marketing on our own.”
Lipocine’s next generation, once-daily, oral TRT, LPCN 1111, is currently in a Phase 2b dose finding study, with top-line results expected in the third quarter this year. The company hopes to meet with the FDA later in the year for an agreement on Phase 3 development.
“We established the feasibility of once-daily dosing in an earlier positive Phase 2a study in hypogonadal men,” Mr. Brown contends.
Lipocine’s LPCN 1107 is an oral formulation of hydroxyprogesterone caproate (HPC) for the prevention of preterm birth. The company has reported positive multi-dose pharmacokinetics (PK) data and is on track to advance to a pivotal study after an end-of-Phase 2 meeting with the FDA in the third quarter.
The current standard-of-care therapy to prevent preterm birth is weekly injections of the drug, Makena. “Twice-daily LN 1107 has the potential to be the first oral standard-of-care therapy and be more efficacious than Makena,” Mr. Brown contends.
Nearly 12% of all pregnancies in the U.S. result in preterm birth, a leading cause of neonatal mortality and morbidity. “Lipocine’s LPCN 1107, which has orphan drug designation from the FDA, is targeting women who already have had a preterm birth, since it is highly likely they will have a second one,” he suggests.
LPCN 1107 also has the potential to optimize clinical outcomes. Mr. Brown says women on Makena require several weeks to reach a steady state of HPC and require weekly visits to a doctor. On the other hand, the potential advantages of LPCN 1107 include reaching a steady state of HPC in seven days and taking the capsule at home.
Ladenburg’s Mr. Kaplan said he was “very encouraged by the positive multi-dose PK data of LPCN1107 and believes that LPCN 1107, if eventually approved, could have significant clinical and commercial advantages over standard-of-care Makena and could expand the HPC preterm birth market.”