TADFIN® (tadalafil 5mg and finasteride 5mg combination) capsules for the initial treatment of men with lower urinary tract symptoms and enlarged prostate

TADFIN® (5mg Tadalafil and 5mg Finasteride tablet) for BPH

Veru is also advancing new drug formulations in its specialty pharmaceutical pipeline addressing unmet medical needs in urology. The clinical trial of the Company’s proprietary TADFIN® (5mg Tadalafil and 5mg Finasteride tablet) for BPH met FDA requirements for bioavailability and bioequivalence for the co-administration of tadalafil 5mg and finasteride 5mg dosed daily for benign prostatic hyperplasia (BPH). Tadalafil (CIALIS®) is currently approved for treatment of BPH and erectile dysfunction and finasteride (PROSCAR® and PROPECIA®) is currently approved for treatment BPH and male pattern hair loss. The co-administration of tadalafil and finasteride has been shown to be more effective for the treatment of BPH than finasteride alone. The Company anticipates submitting an NDA for its Tad-Fin Combination Capsule under the 505(b)(2) regulatory pathway by the end of 2020.

Scientific Overview

Tadalafil/Finasteride combination product in capsules is a new, proprietary formulation that addresses men who have lower urinary tract symptoms and restricted urinary stream because of an enlarged prostate. CIALIS® (tadalafil 5mg) and PROSCAR® (finasteride 5mg) co-administration is indicated for the initial treatment of BPH for up to 26 weeks. CIALIS® (tadalafil 5mg) is a phosphodiesterase 5 (PDE5) inhibitor and PROSCAR® (finasteride 5mg) is a Type 2, 5 alpha reductase inhibitor. Tadalafil 5mg daily has been approved for the treatment of erectile dysfunction and BPH. Finasteride 5mg has been approved for the treatment of BPH: to improve symptoms, to reduce risk of acute urinary retention and the need for prostate surgery, and to prevent progression of BPH.

TADFIN® (5mg Tadalafil and 5mg Finasteride tablet) for BPH

Current Status

Veru’s clinical trial of the Company’s proprietary Tadalafil and Finasteride Combination Capsule met the U.S. Food and Drug Administration’s (FDA) requirements for bioavailability and bioequivalence for the co-administration of tadalafil 5mg and finasteride 5mg dosed daily for benign prostatic hyperplasia (BPH) (TADFIN® Combination Capsule).

Stability testing of commercially manufactured batches (GMP) of the TADFIN® Combination Capsule required for submission of a New Drug Application (NDA) is in progress.

The Company has also requested a Pre-NDA meeting with FDA and anticipates submitting an NDA under the 505(b)(2) regulatory pathway in 2021.

TADFIN® Combination Capsule combines two of the most popular medicines, tadalafil and finasteride, that are currently prescribed separately to treat lower urinary tract symptoms caused by an enlarged prostate also known as BPH. The co-administration of tadalafil and finasteride has been shown clinically to be more efficacious in treating BPH symptoms than either tadalafil or finasteride alone.* Our TADFIN® Combination Tablet is proprietary and is designed to improve patient compliance and safety.

According to current FDA approved labeling, Tadalafil (CIALIS®) (PDE5 inhibitor) is approved to treat both BPH and erectile dysfunction, and Finasteride (PROSCAR®) (5 alpha-reductase inhibitor) is approved to treat symptoms of BPH, prevent the progression of BPH, reduce the risk of acute urinary retention and decrease the potential need for prostate surgery. Finasteride (PROPECIA®) is also approved to treat male pattern hair loss.

*Casabe A et al. J or Urol 2014; 191:717-733

TADFIN® (5mg Tadalafil and 5mg Finasteride tablet) for BPH

Development Plan

In a November 2017 Pre-IND meeting, the FDA confirmed that the Tadalafil/Finasteride combination qualifies for a 505(b)(2) regulatory pathway. The FDA also agreed that a single bioequivalence study and no additional nonclinical, clinical efficacy and/or safety studies will be required to support the approval of the Tadalafil/Finasteride combination for the initial treatment of lower urinary tract symptoms in men with enlarged prostates.  The purpose of the meeting was to discuss the proposed NDA and to confirm the clinical, non-clinical, chemistry, manufacturing, and controls (CMC) requirements for the Company’s NDA submission utilizing the FDA expedited 505(b)(2) regulatory pathway. The Company submitted a pre-NDA briefing document to the FDA that outlined the Company’s preliminary data package being prepared for the NDA submission, including bioequivalence and bioavailability clinical study results, CMC and other regulatory elements for a 505(b)(2) submission. In June 2018, the Company announced that it concluded its pre-NDA meeting with the FDA for TADFIN® (tadalafil 5mg and finasteride 5mg combination) formulation for the treatment of BPH. The Company believes it has reached agreement with the FDA on the regulatory data package requirements that will be sufficient for submission. The FDA requested that the Company submit 12-month stability data on manufacturing batches to support the expiry date of TADFIN® at the time of the NDA submission. The Company plans to submit an NDA for TADFIN® in the second half of calendar year 2020.

TADFIN® (5mg Tadalafil and 5mg Finasteride tablet) for BPH

Clinical

Clinical studies conducted since 2010 have demonstrated that the co-administration of tadalafil with finasteride provides early improvement in lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement (Casabé et al, 2014; Olesovsky & Kapoor, 2016). In addition, tadalafil/finasteride co-administration was also shown to improve erectile function in men who have comorbid erectile dysfunction. Elkelany et al concluded that combination therapy with daily tadalafil and finasteride is ideally suited for men with moderate to severe BPH-LUTS and a prostate volume >30 g. In addition, they conclude that men with coexisting erectile dysfunction will benefit from PDE5 inhibition (Elkelany et al, 2016).

Adverse reactions related to the use of tadalafil and finasteride (separately and co-administered) in clinical trials and from post-marketing experience have been well documented in the approved labeling.

TADFIN® (5mg Tadalafil and 5mg Finasteride tablet) for BPH

Market

The worldwide prevalence of BPH lower urinary symptoms is estimated to be 10-25% of the male population and was estimated to grow to 1.1 billion men by 2018. According to Elkelany O et al. (Therapeutics and Clinical Risk Management 11:507-513, 2015), other men who may benefit from this combination include: 1) men who have a suboptimal response to 5 alpha reductase inhibitors alone (PROSCAR® (finasteride) or AVODART® (dutasteride)); 2) men who have a suboptimal response to an alpha blocker alone (FLOMAX® (tamsulosin), HYTRIN® (terazosin), UROXATRAL® (alfuzosin), CARDURA® (doxazosin), and RAPAFLO® (silodosin)) or in combination with a 5 alpha reductase inhibitor (JALYN® (dutasteride/tamsulosin combination)); and 3) men who have an optimal response to 5 alpha reductase inhibitors, but who also have erectile dysfunction. A Tadalafil 5mg / Finasteride 5mg combination is not currently available. TADFIN®, if approved, would be the first fixed combination of tadalafil and finasteride approved by FDA. TADFIN® would provide clinical benefit both by increasing dosing convenience and drug compliance as poor compliance with a BPH medicine could lead to an increased chance of acute urinary retention, urosepsis, and death. The Company plans to sell TADFIN® through men’s health telemedicine internet channels in the U.S. and to out-license TADFIN® to urology specialty pharmaceutical marketing and sales organizations for upfront payment, milestones, and royalties in territories outside the U.S.