Revolade recommenderas för godkännande av CHMP för godkännande för behandling av aplastisk anemi.

”Today’s CHMP opinion marks a key milestone towards Revolade becoming the first approved therapy in its class in the European Union for patients with severe aplastic anemia who have not responded to or are ineligible for existing treatments,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. ”Our commitment to oncology includes continuing to work towards new treatments for patients impacted by rare diseases like SAA, especially when limited options exist.”

SAA is a blood disorder where the bone marrow fails to make enough red blood cells, white blood cells and platelets[3].Two out of every one million people in Europe and North America are diagnosed with aplastic anemia per year, a portion of which are severe cases[4],[5]. The exact cause of the disease is still unknown, but most cases of SAA are believed to be triggered by an autoimmune reaction where the body attacks blood-forming stem cells located in the bone marrow[3],[6]. As a result, patients with SAA are at risk for life-threatening infectionsor bleeding[6]. 

Treatment of SAA is focused on increasing a patient’s blood cell count. The current standard of care includes IST or hematopoietic stem cell transplantation[6]. Of patients treated with IST, one-quarter to one-third will not respond and 30-40% of responders will relapse, causing symptoms to return[6]. Approximately 40% of SAA patients who don’t respond to initial IST die from infection or bleeding within five years of their diagnosis[1].

The CHMP positive opinion is based on the results of a pivotal open-label Phase II study (ELT112523) and two supporting Phase II studies (ELT116826 and ELT116643) conducted by the National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) . The pivotal study demonstrated a hematologic response (40%) in SAA patients treated with Revolade who had an insufficient response to IST. The most common adverse reactions (>=20%) in the pivotal single-arm study of 43 patients were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%)[7].

The European Commission will review the CHMP recommendation and is expected to deliver its final decision within three months. The decision will be applicable to all 28 EU member states plus Iceland, Norway and Liechtenstein. In August of 2014, eltrombopag (marketed as Promacta® in the USA), was approved by the US Food and Drug Administration for once-daily use in patients with SAA who have had an insufficient response to IST. Eltrombopag is also approved for SAA in Canada.

About the NIH Study

In the single-arm, single-center, open-label Phase II study (NCT00922883), eltrombopag was evaluated in 43 patients with SAA who have had an insufficient response to at least one prior IST and who had a platelet count <=30 x 109/L[8].  At baseline, the median platelet count was 20 x 109/L, hemoglobin was 8.4 g/dL, absolute neutrophil count (ANC) was 0.58 x 109/L, and absolute reticulocyte count was 24.3 x 109/L[8]. The treated population had a median age of 45 years (range 17 to 77 years) and 56% were male. The majority of patients (84%) received at least two prior immunosuppressive therapies[8].

 

Eltrombopag was administered at an initial dose of 50 mg once daily for two weeks and increased over two-week periods up to a maximum dose of 150 mg once daily[8].The primary endpoint was hematologic response, which was initially assessed after 12 weeks of treatment with eltrombopag[8]. Treatment was discontinued after 16 weeks if no hematologic response was observed. Additional efficacy assessments included median duration of response in months[8].

References

[1] Valdez JM, Scheinberg P, Nunez O, et al. Decreased infection-related mortality and improved survival in severe aplastic anemia in the past two decades. Clin Infect Dis. 2011; 52(6):726-735.

[2] Scheinberg P, Young NS. How I treat acquired aplastic anemia. Blood. 2012;120(6):1185-1196.

[3] National Heart, Lung and Blood Institute. What is aplastic anemia? Accessed on May 26, 2015. Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/aplastic.

[4] Young NS, Kaufman DW. The epidemiology of acquired aplastic anemia. Haematologica. 2008; 93(4):489-492.

[5] Montané E, Ibáñez L, Vidal X, et al. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica. 2008; 93(4):518-523.

[6] Townsley DM, Desmond R, Dunbar CE, et al. Pathophysiology and management of thrombocytopenia in bone marrow failure: possible clinical applications of TPO receptor agonists in aplastic anemia and myelodysplastic syndromes. Int J Hematology. 2013; 98(1):48-55.

[7] Promacta Prescribing Information.

[8] US National Institutes of Health. ClinicalTrials.gov Identifier: NCT00922883. A pilot study of a thrombopoietin-receptor agonist (TPO-R agonist), eltrombopag, in aplastic anemia patients with immunosuppressive-therapy refractory thrombocytopenia. Accessed on May 26 2015. Available at: https://clinicaltrials.gov/ct2/show/NCT00922883?term=eltrombopag+and+saa&rank=1.