- Salt Lake City biotech Lipocine has received another Complete Response Letter (CRL) from the Food and Drug Administration for its testosterone drug, slashing its share value by more than a third in Wednesday morning trading.
- According to Lipocine, the letter called for data from an ambulatory blood pressure monitoring study that would provide "definitive evidence" that Tlando, a testosterone replacement therapy, offers clinically meaningful increases in blood pressure for men who have deficiencies of the hormone.
- Regulators also want Lipocine to confirm the reliability of testosterone and maximum serum concentration (Cmax) data connected to Tlando, and to explain why the pre-specified Cmax secondary endpoints for the drug aren't applicable here. Additionally, the biotech must come up with stopping criteria that adequately identify patients who should discontinue Tlando treatment. Lipocine intends to request a meeting with the FDA to iron out the next steps for its drug.
The market for low-testosterone treatments ballooned over the last two decades, due in large part to direct-to-consumer advertising and off-label use of medications. Though diminished levels of the hormone do pose health concerns, including poorer muscle growth and bone density, drugmakers have oriented much of the conversation around erectile dysfunction and lack of a sex drive.
And that has paid off. AbbVie's testosterone gel AndroGel, for instance, holds approvals for a few kinds of hypogonadism and was raking in more than $1 billion a year by 2012.
Yet the therapeutic area hasn't evolved without criticism. In fact, the FDA on multiple occasions issued warnings about testosterone treatments and their intended use.
"FDA has become aware that testosterone is being used extensively in attempts to relieve symptoms in men who have low testosterone for no apparent reason other than aging. The benefits and safety of this use have not been established," the agency wrote in a March 2015 safety announcement.
For Lipocine, the headwinds extend past the therapeutic level. Tlando has now received two CRLs because of regulator concerns about dosing and data validity. The latest rejection isn't a complete surprise; in January, the FDA's Bone, Reproductive and Urologic Drugs Advisory Committee voted 13 to six against the drug's benefit/risk profile.
But the company looks as though it will keep working on Tlando. Like many biotechs, Lipocine's pipeline is relatively sparse. Its next most advanced candidate is just at the doorstep of late-stage testing.
"While we are disappointed by the FDA's decision, the deficiencies identified in the CRL are within our expectations following [the advisory committee meeting]," Lipocine said in a statement. "We are assessing the content of the CRL, including the information that may be needed to resolve the deficiencies."
Morgan Brown, EVP and chief financial officer of Lipocine, said in an email to BioPharma Dive that the ambulatory blood pressure monitoring study is "teed up" but hasn't started dosing yet, though that should begin after the FDA provides feedback about the study protocol. The company expects that feedback by May 15, according to Brown.