Development strategy and status

Envarsus® has completed all necessary Phase lll clinical trials for patients who have undergone a kidney transplant and has completed Phase ll clinical studies for patients who have undergone a liver transplant.

In addition, the company has completed its Phase IIIb/IV STRATO study for Envarsus®. This is not a prerequisite for the regulatory approval of Envarsus®.

Envarsus® in kidney transplant patients (stable patients, study 3001)

This study was completed and preliminary data was released in June 2011. Data from this study was presented at the European Society for Organ Transplantation in September 2011 in Glasgow and at the American Society of Nephrology Renal Week in November 2011 in Philadelphia.

This Phase lll study successfully demonstrated non-inferiority in predefined endpoints compared to Prograf. The Phase lll open label conversion (switch) study in 326 stable kidney transplant recipients, with Prograf as the comparator, met all its primary efficacy and safety endpoints. The study also showed a trend towards superior rejection rates based on central laboratory pathology assessment with rates of 0.6% for Envarsus® and 3.1% for Prograf (p=0.214).

Envarsus® in kidney transplant patients (de novo patients, study 3002)

The positive results of Study 3002 were released in June 2013. Envarsus® successfully demonstrated non-inferiority compared to Prograf®. The Phase III randomized, double-blind and double-dummy study in 543 de novo kidney transplant recipients, with Prograf® as the comparator, met its primary efficacy and primary safety endpoints. The study was conducted under a Special Protocol Agreement with the FDA and the results are considered pivotal for the planned U.S. regulatory filing expected to occur in the second half of 2013.

The primary endpoint of the study was a composite endpoint of treatment failure (biopsy-proven acute rejection or BPAR, graft failure, loss to follow up or death) that was evaluated after a 12-month treatment period to demonstrate the non-inferiority of Envarsus®TM compared to Prograf®. The treatment failure rate for Envarsus®™ was 18.3% compared to 19.6% for Prograf®, well within the 10% pre-specified non-inferiority margin.

Kaplan-Meier analyses showed comparable efficacy throughout the 12-month study period including the early post-operative days when patients are at greatest risk of organ rejection and graft failure. Within the first 3 months after transplant, when patients are at the greatest risk of rejection, the treatment failure rates for Envarsus®TM and Prograf® were 10.4% and 14.2%, respectively (p=0.124).

The study results demonstrated that during long-term outpatient therapy from Month 3 onwards, Envarsus®TM patients required a daily dose that was approximately 15 percent lower than patients receiving Prograf®, reflecting the improved absorption provided by Veloxis' proprietary MeltDose® formulation.

Envarsus® regulatory strategy

Based on the favorable results of study 3001 and the totality of an extensive Phase I, II and III clinical safety, efficacy and pharmacokinetics programme, the Company filed an MAA in the European Union in April 2013. In December 2013, the Company announced that it had submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for the marketing and sale of Envarsus® in the U.S. for the prevention of organ rejection in kidney transplant recipients. The submission is based on the entire data set from the company's clinical development program that comprised 25 studies and enrolled over 1000 patients, including two pivotal clinical trials, studies 3001 and 3002. Envarsus® was granted Orphan Drug status by the U.S. Food and Drug Administration (FDA) for prophylaxis of organ rejection in patients receiving allogenic kidney transplants.

Kidney transplant phase IIIb programme

Veloxis has initiated one Phase IIIb/IV study and plans to initiate several additional studies to further examine the potential clinical differences between Envarsus® and existing therapies, including Prograf.

STRATO (Switching kidney TRAnsplant patients with Tremor to LCP-tacrO - Study 3003)

This was a phase IIIb study of Envarsus® in kidney transplant patients experiencing tremors on standard tacrolimus formulations. It was designed to explore whether converting patients who have symptomatic tremor from treatment with standard twice-daily tacrolimus capsules (such as Prograf) to sustained release once-daily Envarsus® tablet, leads to a measurable improvement in tremor. Final results were announced in May 2013 demonstrating the potential for Envarsus® to improve tacrolimus-induced tremors in stable kidney transplant patients when switching from twice-daily tacrolimus to once-daily Envarsus®.

ASERTAA (A Study of Extended Release Tacrolimus in African-Americans) Phase IIIb study of Envarsus®

The ASERTAA Phase IIIb study of Envarsus® (formerly LCP Tacro™) in kidney transplant recipients. The ASERTAA study is designed to compare the pharmacokinetics (PK) of Envarsus®, a once-daily tacrolimus tablet, to generic twice daily tacrolimus capsules in stable African-American renal transplant patients.