In 2012, more than 50,000 organ transplants were conducted in the US, Japan, the United Kingdom, France, Germany, Italy and Spain.
The immunosuppression market comprises several different classes of compounds. The main class of immunosuppressants is the calcineurin inhibitors (CNIs), which includes tacrolimus (Prograf® and Advagraf® / Astagraf XL (Astellas Pharma Inc.) and generics of Prograf®) and cyclosporine (Neoral® and Sandimmune® (Novartis AG) and generics). The worldwide sales of non-generic Prograf® and Advagraf® were reported by Astellas Pharma Inc. to be JPY 161.8 billion (approximately USD 1.95 billion) for 2012 (Astellas Pharma Inc. Annual Report FY 2012). Sales of non-generic cyclosporine (Neoral and Sandimmune), for which generic versions have been available since 2000, were reported to be USD 750 million for 2013 (Novartis AG Annual Report FY 2013). The CNIs are the principle class of agents that will compete with Envarsus® for sales, together with Nulojix® (belatacept), which was launched by Bristol-Myers Squibb Company ("BMS") in 2011 and achieved sales of USD 8 million in 2013 (BMS Annual Report 2013).
The transplant marketplace in the United States is ideally suited for a small and well-focused selling effort and the clinical practice of transplant medicine leads to a unique commercialisation opportunity. Transplants are generally performed at a small number of highly specialised centres, of which there are approximately 250 in the entire United States.
Patents waiting for a transplant will often travel considerable distances for transplant at one of these few centres. As such, a limited number of sales representatives can cover the majority of the centres. During a sales visit, a representative can effectively call upon all professionals involved in the transplant process including surgeons, nephrologists, infectious diseases specialists and pharmacists. On a targeted basis, community nephrologists with large numbers of transplant patients would also be included for field force coverage.
Over the past 20 years, a number of new immunosuppression medications have been approved, increasing the number of options available and facilitating a noticeable evolution in therapeutic protocols. While CNIs continue to be used for maintenance immunosuppression in most patients, there has been a change in the preference of CNI used, from cyclosporine to Astellas Pharma Inc.'s tacrolimus (Prograf). Immunosuppression can be achieved with many different drugs, including steroids, targeted antibodies and CNIs like tacrolimus. Of these immunosuppressants, tacrolimus is one of the most potent in terms of suppression of the immune system. Tacrolimus for systemic use is currently available worldwide as a twice-daily dosage formulation, Prograf (Astellas Pharma Inc.), and in Europe, since June 2007, it has also been available as a once-daily dosage formulation, Advagraf (Astellas Pharma Inc.). Advagraf attained EUR 144 million in sales in 2011 in the European Union (Astellas Pharma Inc. FY2011 Financial Results). In July 2013, Advagraf was approved in the U.S. for the prevention of organ rejection in kidney transplants. Nulojix (belatacept, BMS), an infusional biologic agent, achieved U.S. and EU approval in June 2011. However, the initial sales has been modest.
The current market consists of Astellas Pharma Inc.'s Prograf (twice-daily) and generic equivalent tacrolimus products, as well as Astellas Pharma Inc.'s Advagraf (once-daily), which is currently marketed outside the United States and would likely be a key competitive product to Envarsus® in, specifically, countries within the European Union. In particular, major pharmaceutical companies such as Sandoz (a Novartis AG company), Accord Healthcare Ltd., Watson Pharmaceuticals, Inc., Dr. Reddy's Laboratories Ltd. and Mylan Laboratories, Inc. are active generic market participants in the immunosuppression market.
At present, there is no once-daily version of tacrolimus available in the United States. In September 2012, Astellas Pharma Inc. announced that they had submitted an application to the FDA seeking approval in the United States for tacrolimus extended release capsules (Advagraf) for the prophylaxis of organ rejection in adult kidney transplant recipients and adult male liver transplant recipients. Generic versions of Prograf became available in the United States in 2009 and in the European Union in 2010. Generics have attained a 64% share of the tacrolimus market in the United States as at 12 April 2012 (source: Astellas Pharma Inc. FY2011 Financial Results). Envarsus® will not be an AB-rated generic equivalent of tacrolimus, and therefore generics of tacrolimus cannot automatically substitute for Envarsus®.