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Myeloproliferative neoplasms (MPN) include chronic myeloid leukemia (CML), essential thrombocythemia (ET), myeloid fibrosis (MF), and polycythemia vera (PV).
 
   
  Polycythemia Vera (PV)
 

The prevalence of PV is 0.02% (2 in 10,000 people) in the US, 0.03 % in Europe, and 0.01% in Japan, respectively. The annual incidence is estimated at approximately 0.001-0.003% (1 to 3 new patients per 100,000 people per year) in the US and Europe and 0.002% in Japan. The estimated patient population is approximately 100,000 in US and 150,000 in Europe.

Some patients with PV may not have any symptoms; others may have symptoms such as itching, tiredness, headaches, blurred vision, an enlarged liver and spleen. Patients who suffer from more severe symptoms may develop blood clots, which can form in almost any blood vessel, causing heart attacks and strokes. Without treatment, about half of all PV patients with symptoms die in less than two years (Tefferi 2005, Campbell 2005). With treatment, patients can live on an average of 15-20 years. Nevertheless, the long-term treatment for patients with PV is still unsatisfactory, and the disease remains incurable (Vannucchi et al., 2010).

Currently, there is no efficacious treatment for PV except by regular phlebotomy or cytotoxic therapy, hydroxyurea. However, phlebotomies can cause iron deficiency in patients and can be dangerous to elderly and people with cardiovascular diseases. Hydroxyurea can also cause troublesome side effects and the main concern is the long term transformation to AML. Several formulations of interferon have been used in the past (off-label), but these have been hampered by a very unfavorable side effect profile (depression, flu-like syndrome).

As a consequence, most existing PV treatment options are sub-optimal and both clinicians and patients are still seeking a treatment that can be a potential cure for this disease, while being efficacious, with an acceptable adverse event profile, and convenient.

There is good evidence that IFN-α may have a positive effect on the progression of PV (Kiladjian 2008, Tefferi 2005, Campbell 2005, Elliott 1997, Quintas-Cardama 2009, Hasselbalch 2011). However, its use is limited by the toxicity, leading to discontinuation of treatment in ~20% of patients. Most notable side effects include neuropsychiatric and flu-like symptoms.

An institutional sponsored Phase II trial of Pegasys on PV patients performed by Kiladjian (Blood, 15/10/2008, 112, No. 8) showed significant clinical and molecular responses and tolerance in the 37 patients enrolled, with a median follow-up of 31.4 months. After 12 months, 35 out of the 37 patients showed hematologic complete response. 81% of patients showed relapse-free survival at three years after they stopped receiving peg-IFN. However, 10 out of 37 patients (27%) had to stop the treatment because of toxicity associated with treatment. Nonetheless, the study from Kiladjian still provided good evidence that IFN-alpha has beneficial effects on PV.

Ropeginterferon alfa-2b (also as known as AOP2014) is likely to present a better opportunity for both efficacy and safety. In our Phase I/II study, after one year treatment, ~90% of patients showed responses, with 45-50% complete response rates. Ropeginterferon alfa-2b has also demonstrated disease modifying activity in PV patients (demonstrating downregulation of JAK2 allele burden).

PharmaEssentia has licensed the rights to ropeginterferon alfa-2b for myeloproliferative disorders in Europe, Middle East, and CIS to AOP Orphan (Vienna, Austria). PharmaEssentia retains rights for ropeginterferon alfa-2b in all other territories (including the US).

Ropeginterferon alfa-2b was granted an Orphan Designation by EMA in 2011 for the treatment of PV. Ropeginterferon alfa-2b also has Orphan Drug Designation in the US. Currently, ropeginterferon alfa-2b is in a registrational Phase III trial (PROUD-PV) in the EU (trial design has been agreed upon with EMA).
   
Neutropenia
   
 

Neutropenia is a condition in which the number of neutrophils (white blood cells) in the bloodstream is reduced, often due to cancer chemotherapy. A reduced number of neutrophils can cause serious infections and lead to severe complications, even death.

   
Anemia
   
 

Anemia is a condition characterized by a decrease in number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood, often caused by chronic kidney disease. People with anemia commonly feel fatigue, general malaise, and sometimes poor concentration. In very severe anemia, the condition may cause cardiac problems, even heart failure.

   
  PEG-EPO
 

PEG-EPO can reduce discomfort from anemia, caused by chronic renal failure or chemotherapy. PharmaEssentia is currently pursuing its own pegylated EPO which is currently in early stage trials.



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