By John Vandermosten, CFA
Update on Validation Trial for Tlando
On December 5th Lipocine Inc. (NASDAQ:LPCN) announced that it will begin its dosing validation study for LPCN 1021 (Tlando) immediately to address the items raised in the CRL in June of this year. The company received feedback from the FDA regarding desired size and duration of the study and felt this information was sufficient to commence with the trial. Completion is targeted within the next 60 to 90 days. LPCN did not develop a full agreement with the FDA as management felt it would take longer than the anticipated duration of the trial to obtain it. As of late December, Lipocine has started screening patients for the validation effort and we expect the first enrollees began the test therapy before the end of 2016 and full enrollment to be complete in a couple months. Topline results are anticipated by 2Q:17 targeting the same endpoints as used in the Phase 3 trial.
The dosing validation trial is an open-label, fixed dose, single treatment arm of Tlando which expects to enroll 100 subjects. The dosing period is 24 days and the primary endpoint is the percentage of subjects with an average 24-hour serum testosterone concentration average (“Cavg”) within the normal range. Secondary endpoints will examine maximum serum testosterone concentrations (“Cmax”).
The company has also initiated a dosing flexibility study, as announced in a January 5th release. This study will provide a daily dose of 450 mg, divided into three equal parts, whereas the dosing validation study is examining the 450 mg daily dose divided in two. Timing for the dosing flexibility study targets first enrollment in 1Q:17 and results available by 2Q:17. Trial design will match that of the dosing validation trial and will include the same primary and secondary endpoints.
The purpose for initiating the second validation trial was for both commercial and regulatory reasons. From a commercial perspective, the additional trial data may provide sufficient evidence for either twice daily or three times daily dosing, allowing for additional flexibility in the label when it is determined. From a regulatory perspective, the data will provide additional information in the resubmission to achieve greater compliance with the Cavg and Cmax constraints.
The FDA will analyze the new data from the validation and flexibility trials along with the resubmission and we anticipate that this will be followed by a 6-month review by the FDA and a 4Q:17 answer from the agency. If Tlando is approved, first sales are expected by early 2018.
Completion of FDA Post Action Meeting
On October 17, 2016, the company announced that it had held a Post Action meeting in the first half of October with the FDA following the receipt of a Complete Response Letter (CRL) on June 28 of this year. The meeting was held in order to clarify the deficiencies noted in the CRL and assist Lipocine in determining what is necessary to obtain approval of LPCN 1021 (Tlando).
The CRL had identified deficiencies in the dosing algorithm when comparing the protocol used in the trial with the data provided on the drug label. As a result, the FDA required an additional trial to validate the proposed label. In response, Lipocine submitted a new dosing validation clinical study protocol to the FDA.
On August 28, 2015, Lipocine Inc. submitted a 505(b)(2) New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Lipocine’s lead asset LPCN 1021. LPCN 1021 is a testosterone replacement therapy (TRT) designed for oral twice daily dosing in adult hypogonadal males with low testosterone. The FDA accepted the NDA on October 29, 2015, and subsequently on November 12, 2015, Lipocine announced that the FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 28, 2016 for completion of the review of the NDA. The FDA issued a CRL in June 2016, and met with Lipocine in October 2016 for a Post Action meeting that provided additional clarity on trial design and future steps required for resubmission to the FDA.
The CRL highlighted deficiencies related to dosing as provided in the label. The Phase 3 trial protocol had adjusted dosing based on 15 blood draws taken over a 24 hour period; however, the proposed label only relied on only one blood draw to determine the proper titration. The FDA felt that this inconsistency would lead to dosing errors and as a result will require evidence to support a single point window after administration of Tlando where the patient is evaluated and up-titrated or down-titrated to achieve the optimal dose. Prior to the letter, management felt that the trial design was sufficient as it was based on the Phase 3 trial for Axiron, an Eli Lilly topical testosterone product which was approved in 2010.
We continue to believe the oral formulation of LPCN 1021, if approved, may improve patient compliance as it appears to be a generally safe, effective, and a more convenient TRT option as compared to topical and injectable TRT products that are currently on the market. LPCN 1021 will have to adhere to all of the new regulations set forth by the FDA if approved. For instance, cautionary language will be required on the label for possible cardiovascular and stroke related risk with TRT, and the lack of benefit and safety of TRT in age-related hypogonadism.
Additionally, if LPCN 1021 is approved, there may be post-approval obligations regarding a heart attack and stroke risk study. Lipocine may be have to contribute to an on-going industry-led heart attack and stroke risk study, or it may need to conduct a separate long-term study.
We expect a 4Q:17 FDA announcement date for Tlando with a subsequent launch of the product in early 2018. We believe that the FDA’s emphasis on dosing protocols rather than on a fundamental flaw with the Lip’ral technology support eventual approval. We maintain a positive view on Lipocine shares as an investment in the specialty pharmaceutical sector based on the company’s promising pipeline and Lip’ral technology. While the FDA’s issuance of a complete response letter will delay the launch of Tlando and increase trial costs by several million dollars, we believe that Lipocine will obtain approval for the compound.
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