Lipocine Inc.

Discussion in 'Men's Economics' started by Michael Scally MD, Nov 4, 2013.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Lipocine Inc.
    Lipocine - Home

    Lipocine Inc. is a specialty pharmaceutical company focused on applying our oral drug delivery technology for the development of pharmaceutical products in the area of men’s and women’s health. Their lead product candidate, LPCN 1021, is a Phase III-ready oral testosterone replacement therapy, or TRT, designed for convenient twice-a-day dosing. They have filed a S-1: Form S-1
     
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Lipocine Announces Positive Top-Line Results in Its Phase 3 Study of LPCN 1021 for Oral testosterone Replacement Therapy
    http://ir.lipocine.com/releasedetail.cfm?ReleaseID=872351

    · Met primary efficacy endpoint by successfully restoring testosterone levels to the normal range in 88% of the subjects
    · Lower limit of the 95% confidence interval was 82%
    · 85% of the subjects reached final dose with no more than one dose titration
    · Majority of subjects ended on 225 mg BID
    · Proportion of subjects with maximum serum concentrations generally met FDA pre-specified targets
    · LPCN 1021 treatment was well tolerated with no drug related serious adverse events

    SOAR is a randomized, open-label, parallel-group, active-controlled, Phase 3 clinical study of oral TRT in hypogonadal males with low testosterone ( < 300 ng/dL). In total, 315 subjects at 40 active sites were assigned, such that 210 were randomized to LPCN 1021 and 105 were randomized to the active control, for 52 weeks of treatment.

    The active control is included for safety assessment. LPCN 1021 subjects were started at 225 mg Testosterone Undecanoate ("TU") (equivalent to ~ 142 mg of T) twice daily ("BID") with a standard meal and then dose titrated, if needed, up to 300 mg TU BID or down to 150 mg TU BID based on serum testosterone measured during weeks 3 and 7.
     
  3. DTdr2

    DTdr2 Member

  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    FDA Accepts for Filing Lipocine's New Drug Application for Its Oral testosterone Replacement Product Candidate, LPCN 1021
    http://ir.lipocine.com/releasedetail.cfm?ReleaseID=939326

    SALT LAKE CITY, Oct. 29, 2015 (GLOBE NEWSWIRE) -- Lipocine Inc. (NASDAQ:LPCN), a specialty pharmaceutical company, today announced that the U.S. Food and Drug Administration ("FDA") has accepted for filing its New Drug Application ("NDA") for LPCN 1021, an oral testosterone product candidate for testosterone replacement therapy ("TRT") in adult males for conditions associated with a deficiency or absence of endogenous testosterone ("hypogonadism"). The acceptance by the FDA of the NDA indicates that the application is sufficiently complete to permit a substantive review.

    LPCN 1021 is a novel twice-a-day, oral testosterone replacement therapy product candidate with three simple oral dosing options that Lipocine expects will overcome the major shortcomings of existing products. The current testosterone market is dominated by topical products that carry FDA "black box" warnings related to inadvertent transfer of testosterone and by injectable products. The IMS Health database shows that an average of half a million prescriptions per month has been dispensed so far in 2015 for TRT.
     
  5. Millard Baker

    Millard Baker Member

    I wonder if LPCN 1021 (testosterone undecanoate) is just another Andriol clone? Or is the Lip'ral drug delivery technology really any better?

    And what is LPCN 1111? I can only find it listed as a novel next generation prodrug of testosterone. Is this the first "prohormone" marketed for TRT?
     
  6. Millard Baker

    Millard Baker Member

    "LPCN 1111 is in a very early stage of development, has never been administered in our targeted male population, and may not be further developed for a variety of reasons.

    "LPCN 1111 is in a very early stage of development. We currently have preliminary data demonstrating absorption of LPCN 1111 in dogs and in postmenopausal females. To our knowledge, this novel ester prodrug has never been administered orally in hypogonadal males and its safety has never been assessed in animal studies. Our proof-of-concept Phase I/II study would be the first study of this prodrug in hypogonadal males through oral administration. We may not be able to demonstrate through such study that LPCN 1111 has adequate, or any, oral absorption in hypogonadal males to warrant further development or that the safety profile warrants further development.

    "In addition, the active ingredient in LPCN 1111 has only been manufactured on a small scale. Scale up into larger batches could be challenging and our ability to procure adequate material in a timely manner to further develop LPCN 1111 is uncertain. We also may not have a manufacturer who can supply adequate quantities of the drug substance in compliance with cGMP.

    "We have not submitted an IND with the FDA to conduct the proof-of-concept Phase I/II study in hypogonadal males. We recently completed a pre-IND meeting with the FDA in which we broadly discussed the requirements for a NDA filing for LPCN 1111. Several factors could significantly affect the prospects for LPCN 1111, including relating to the regulatory approval and clinical development challenges discussed above. Even assuming successful proof-of-concept Phase I/II study, the anticipated Phase III program for a NDA filing for LPCN 1111 would be very long and expensive."
     
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine


    Lipocine Receives Complete Response Letter (CRL) for LPCN 1021 From U.S. Food and Drug Administration

    Lipocine Receives Complete Response Letter (CRL) for LPCN 1021 From U.S. Food and Drug Administration - NASDAQ.com

    Lipocine Inc. (NASDAQ:LPCN), a specialty pharmaceutical company, today announced that it has received a Complete Response Letter ("CRL") from the United States Food and Drug Administration ("FDA") regarding its New Drug Application ("NDA") for LPCN 1021, an oral testosterone product candidate for testosterone replacement therapy ("TRT") in adult males for conditions associated with a deficiency or absence of endogenous testosterone, also known as hypogonadism.

    A CRL is a communication from the FDA that informs companies that an application cannot be approved in its present form.

    The CRL identified deficiencies related to the dosing algorithm for the label. Specifically, the proposed titration scheme for clinical practice was significantly different from the titration scheme used in the Phase 3 trial leading to discordance in titration decisions between the Phase 3 trial and real-world clinical practice.

    The next step will be to request a meeting with the FDA to understand more fully the issues raised and to agree on a path forward to achieve approval of LPCN 1021.
     
  8. Nissan

    Nissan Member

    Lipocine Completes Enrollment in the LPCN 1021 Fixed Dose Clinical Trials
    Lipocine has complete enrollment for the DV and DF studies thereby addressing the deficiency cited in the FDA's Complete Response Letter. Data is expected in June.

    Lipocine Completes Enrollment in the LPCN 1021 Fixed Dose Clinical Trials
     
  9. Nissan

    Nissan Member

    Lipocine announces LPCN 1021 achieved primary endpoints confirming the efficacy of twice daily oral administration. NDA planned for third quarter of 2017 @Michael Scally MD
     
  10. Kinetic

    Kinetic Member

    I followed the links and saw that a few participants had HCT and PSA issues, which would be expected for some on any TRT method, but I didn't see anything addressing liver values post-therapy. Did I miss it or is it safe to assume that oral administration doesn't have any significant impact on the liver?
     
  11. grey

    grey Member AnabolicLab.com Supporter

    If memory serves, the absorption/delivery pathway is the lymphatic system bypassing the liver. Sam as Andriol.

    Basically not hepatoxic.
     
  12. Nissan

    Nissan Member

  13. Nissan

    Nissan Member

    Lipocine re-filed NDA for LPCN 1021 and was accepted for review by FDA. Decision expected in Feb'18.
     
    Michael Scally MD likes this.
  14. Nissan

    Nissan Member

    Lipocine will be in front of an FDA advisory committee for their NDA on Jan 10th.
    I think they get approved this time around. Thoughts @Michael Scally MD
     
    grey likes this.
  15. Nissan

    Nissan Member

    In other news, FDA rejected Antares Pharma's Xyosted (QuickShot), a testosterone enanthate subcutaneous auto injector.
    FDA cited increase in blood pressure, occurrence of depression and suicidality in the refusal letter.
     
    Michael Scally MD likes this.
  16. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    FDA Rejects Xyosted for Hypogonadism
    FDA Rejects Xyosted for Hypogonadism

    The US Food and Drug Administration (FDA) has rejected the QuickShot Testosterone (XYOSTED) for the treatment of low testosterone levels associated with hypogonadism in adult males, announced Antares Pharma.

    Antares Pharma received a response letter from the FDA regarding the New Drug Application (NDA) indicating that the FDA cannot approve XYOSTED in its present form.

    The letter identified 2 deficiencies related to clinical data based on findings in studies QST-13-003 and QST-15-005.

    The FDA expressed concern that XYOSTED could cause a meaningful increase in blood pressure, as well as questioned the occurrence of depression and suicidality. No Chemistry, Manufacturing and Controls (CMC), device or efficacy issues were noted in the letter.

    On Oct. 12, Antares Pharma announced it received notice from the FDA which identified unnamed deficiencies preventing the drug from moving forward in the labeling and postmarketing requirements process. In the letter, the FDA did not specify the deficiencies.

    The drug-device combination product delivers testosterone enanthate using a subcutaneous auto injector for adult males with low testosterone associated with hypogonadism. XYOSTED is being designed an at home, weekly, self-administered testosterone replacement option.

    XYOSTED is designed to allow the rapid subcutaneous self-administration of highly viscous drugs like testosterone and biologics using a high spring pressure through a fine gauge needle. Phase 3 data showed that testosterone delivered provided rapid, steady and reliable efficacy by restoring testosterone to pre-defined physiologic levels.
     
    Millard Baker, grey and Nissan like this.
  17. Nissan

    Nissan Member

    In yet another setback for Lipocine, FDA panel yesterday voted 6 to 13 recommending the FDA not approve the drug.
    The FDA is expected to make a formal decision on May 8th, 2018.
     
    Michael Scally MD likes this.
  18. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    FDA Advisers Slam Lipocine's testosterone Pill, Raising Doubts About 'Low T' Drugs
    FDA Advisers Slam Lipocine's Testosterone Pill, Raising Doubts About 'Low T' Drugs

    Shares of testosterone drug developer Lipocine lost more than half their value today, plummeting to $1.73, after an advisory panel to the FDA voted overwhelmingly against the prospect of the agency approving Tlando, the company’s oral testosterone treatment. By a vote of 13 to six, the advisers determined that the risks of the product do not outweigh the benefits. The FDA doesn’t have to follow the advice of its advisory panels but it usually does, and the verdict clearly raised doubts in the minds of investors about the prospects for Lipocine’s product. https://www.fda.gov/downloads/Advis...iveHealthDrugsAdvisoryCommittee/UCM591569.pdf

    The questions raised during the advisory panel meeting on Wednesday hint at a broader trend, however—one that calls into question the future of testosterone drugs meant to treat “low T,” a disorder that was popularlized over a decade ago, when TV ads for hormone gels like AbbVie’s androgel flooded the airwaves. AndroGel is now one of six companies being tried in a class action lawsuit in a U.S. District Court in Illinois. The case involves more than 4,000 men who allege that the companies downplayed the cardiovascular risks of testosterone drugs and that they suffered heart attacks, strokes and other problems as a result. That makes for a tough backdrop for Lipocine and any other company seeking to develop new low-T products.

    Cardiovascular safety issues associated with Lipocine’s Tlando topped Wednesday’s agenda for the FDA advisory panel. A briefing document released prior to the meeting noted that in a year-long trial comparing Tlando with AndroGel, both products raised heart rate and one dosage of the Lipocine drug caused an increase in systolic blood pressure. The advisers also looked at increases in hemocrit, or the volume of red blood cells, which can raise the risk of heart attack and stroke. During the trial, eight patients taking Tlando experienced an increase in hemocrit levels, vs. just one who was taking AndroGel.

    This is Lipocine’s second shot at FDA approval for Tlando. The agency gave the product a thumbs-down in 2015 after raising questions about how testosterone levels were measured during clinical trials and noting that several secondary endpoints for efficacy were not met. Questions about the measurement of testosterone levels were also raised during yesterday’s panel meeting.

    "We continue to believe that efficacy and safety results from numerous clinical studies with TLANDO are consistent with other FDA approved TRT products," said Mahesh Patel, chief executive officer of Lipocine in a statement. "We look forward to continuing to work with the FDA through the remainder of the review process." The FDA will make its final decision by May 8.

    The FDA has approved testosterone replacement products like AndroGel to treat hypogonadism, a drastic drop in levels of the hormone that’s caused by a legitimate medical problem. But off-label use of the drugs to treat normal symptoms of aging, like fatigue and loss of libido—maladies that all of those ads cited as signs of low T—helped turn some testosterone gels into $1-billion-a-year blockbusters. The FDA advisory panel was clearly aware that the same trend could come into play with Tlando.

    The potential for Tlando to raise the risk of cardiovascular side effects “is relevant not only to the small population of men with classic hypogonadism,” the briefing document said, “but also to the much larger middle-aged and older population who are receiving testosterone therapies for uses that are not FDA-approved.”

    The FDA has taken steps over the years to raise awareness of cardiovascular risks associated with testosterone products. The agency ordered makers of the products to revise labels so it would be clear that the drugs are meant to treat hypogonadism, not aging, and that they could cause heart issues. They also ordered post-marketing studies to further elucidate the risk of side effects.

    The notion that drugmakers are to blame for putting men at risk of side effects from testosterone has resonated somewhat with jury members in the ongoing class action suit against AbbVie and others in Illinois. AbbVie was ordered to pay $140 million in damages to one man and $150 million to another after losing lawsuits in which the men alleged that AndroGel caused their heart attacks. The company has been appealing the verdicts, and last month the court threw out the $150 million award and ordered a new trial, which is set to start in March.

    The legal battle has so far been easier for Endo, maker of the testosterone drug Auxilium: It was cleared of liability in a case brought by a man in Tennessee who blamed the product for his heart attack. The company is still facing more than 1,200 suits associated with the product, according to its latest quarterly filing.

    Just how the class action proceedings will balance out in terms of determining whether testosterone makers are guilty of underplaying the risks of their testosterone products has yet to be seen. But it’s clear that any company seeking to introduce a new testosterone drug into this contentious market will face significant challenges. Just one day before the FDA advisory panel disappointed Lipocine’s investors with its negative review of Tlando, it handed a no-go vote to Clarus Therapeutics for its testosterone drug, Jatenzo. This is also Clarus’s second attempt at FDA approval.
     
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