After having demonstrated positive Phase 2 pharmacokinetic (PK) data in stable transplant patients earlier this year, LCP had successful discussions with the U.S. Food and Drug Administration (FDA) regarding the further development of LCP-Tacro™ once-daily tablets. The FDA acknowledged the Company's strategy of submitting a §505(b)2 application for LCP-Tacro™, thereby making use of existing literature data to support the application for prevention of organ rejection in kidney and liver transplant patients. To further support the safety database and potentially best in class pharmacokinetic profile for LCP-Tacro™, LCP agreed with the FDA to perform PK-studies in de novo kidney and liver transplants. The results from these ongoing studies, which are expected in first half of 2009, are expected to confirm the superior pharmacokinetic profile of LCP-Tacro™ over existing tacrolimus formulations (Prograf®) in de novo transplant patients. The pivotal clinical program in liver patients awaits discussions with FDA in the first half of 2009.
"The initiation of the clinical Phase 3 program for LCP-Tacro™ tablets is a significant step forward in the development of our organ transplantation program as well as in our plans to become a specialty pharmaceutical company. The team has done a tremendous effort to get us to this stage and we all feel proud of having achieved this important milestone," says Dr. Karin Hamberg, Executive Vice President of R&D and CMO of LCP.
"This is the start of an exciting clinical development program. LCP-Tacro™ will bring the convenience of once-daily administration of tacrolimus which may improve adherence and may optimize outcomes after kidney transplantation," says Steven M. Steinberg, MD, Medical Director, Multiorgan Transplant at Sharp Memorial Hospital, San Diego, California, USA, and a clinical investigator in the Phase 3 study.
About LCP-Tacro™ (Kidney) Phase 3 Clinical Trial Design
This Phase 3 clinical study is a 2-armed parallel group, prospective, randomized, open-label, multi-center, non-inferiority trial to establish the efficacy and safety of conversion from maintenance immunosuppressive therapy with Prograf® capsules twice daily to LCP-Tacro™ tablets once daily for the prevention of organ rejection in stable adult kidney transplant patients. Patients having received a kidney transplant between 3 months and 5 years earlier and treated with a stable dose of maintenance immunosuppressive therapy with Prograf® will be randomly assigned to remain on maintenance therapy with Prograf® capsules twice daily or to be converted to LCP-Tacro™ tablets once daily with a 30% reduced daily dosage. Patients entered in the study will be treated with the assigned study drug adjusted according to whole blood tacrolimus trough levels and will be followed for one year after randomization. A composite endpoint consisting of death, graft failure, biopsy-proven acute rejection or loss to follow up within 12 months after randomization will be the primary outcome measure.
About LCP-Tacro™ & Tacrolimus
Tacrolimus is a leading immunosuppressive medication to prevent rejection after organ transplantation. LCP-Tacro™ is being developed as a once‐daily tablet version of tacrolimus with improved bioavailability and reduced variability in absorption when compared to Astellas' twice daily version of tacrolimus (Prograf® worldwide) and its prolonged‐release version of tacrolimus for once daily administration (Advagraf® in Europe). Clinical trials have demonstrated that LCP-Tacro™ has a superior bioavailability and PK profile and is expected to provide significant improvements for patients currently on Prograf®.
Transplant patients need to maintain a minimum level of tacrolimus in the blood to prevent organ rejection; however, too high levels increase the risk of serious side effects such as kidney damage or hypertension. Therefore, tacrolimus levels need to be managed carefully and transplant patients typically are obliged to make frequent visits to the hospital for monitoring and dose adjustments for months after receiving a new organ. Management of tacrolimus levels is complicated by the low bioavailability of Prograf®, its variable absorption and interaction with food and other drugs. The current market size for immunosuppressants used in transplantation in the seven major markets (US, Japan, France, Germany, Italy, Spain and UK) is approximately $3.3B and growing by approximately 5‐10% per year. In 2007, worldwide sales of tacrolimus were approximately USD 1.6 billion out of which approx. USD 825 million were sales in North America (IMS, all rights reserved).
About transplantation and kidney transplantation
In order to prevent the patient's immune system from rejecting the transplanted organ, immunosuppression therapy is required for the lifetime of the graft in conjunction with a base maintenance drug and adjunctive therapies. In 2007, about 47,000 solid organ transplants were conducted in seven major markets (U.S., Japan, France, Germany, Italy, Spain, and the United Kingdom) (Datamonitor 2008, all rights reserved). The number of transplant patients waiting for organs is expected to continue to outpace the number of organs available.
Kidney transplantation is normally recommended for patients with end-stage kidney disease or kidney failure caused by severe, uncontrolled hypertension, diabetes, infections, intoxication, or inflammation. Kidney transplants account for approximately 60% of all transplants performed annually in the seven major markets, and kidney transplants generally offer the best outlook for patients with end-stage kidney disease. Most centers have patient and organ survivals of over 90% at one year, and more than 80% at three years. Approximately 50% of transplanted kidneys are still functional after 10 to 15 years.
About LifeCycle Pharma A/S (LCP)
Based in Hørsholm, Denmark, with an office in New York, LCP is an emerging specialty pharmaceutical company. Clinical development is the core of LCP's effort to develop a product portfolio which includes products for immunosuppression, specifically organ transplantation, and products to combat certain cardiovascular diseases. As a fully integrated company, LCP adapts new technologies on a fast commercial timetable. LCP's unique, patented delivery technology, MeltDose®, can improve absorption and bioavailability - at low-scale up costs - not only for a broad spectrum of drugs already on the market but also for new chemical entities. LCP has a cholesterol-lowering product, Fenoglide™, currently on the U.S. market and a diversified near- and medium-term pipeline with five product candidates in clinical trials and one in preclinical development. LCP is listed on the OMX Nordic Exchange Copenhagen under the trading symbol (OMX: LCP). For further information, please visit http://www.lcpharma.com.