Ceplene

Indication

Acute Myeloid Leukemia Remission Maintenance Therapy

 

Target Population

EU Big 5 34,000 patients
Total EU 47,000 patients

 

Description

Histamine Dihydrochloride

 

Dosage and Administration

Ceplene®: 0.5 mg, bid, sub-q Interleukin-2 (Proleukin®): 16,400 IU/kg, bid, sub-q
Treatment comprises 10 cycles
3 cycles comprised of 3 weeks of treatment, followed by 3 weeks of rest
7 cycles comprised of 3 weeks of treatment, followed by 6 weeks of rest

 

Adverse Reactions

Well tolerated with mild flushing, headache and fatigue
Ceplene® IL-2 self-administered at home

 

Description

Ceplene® (histamine dihydrochloride) is administered in conjunction with low dose interleukin-2 (IL-2), for maintenance of first remission in patients with Acute Myeloid Leukemia (AML). It has been shown in clinical studies to prevent leukemic relapses in AML patients in first remission and prolong leukemia-free survival while maintaining good quality of life during treatment.

AML patients receive intensive induction treatment with chemotherapeutic drugs at diagnosis, and typically become free of detectable leukemia, achieving “complete remission”. However, despite ensuing consolidation therapies, within 1-2 years the majority (75-80%) of adult patients will experience a relapse of leukemia, of which survival prognosis is extremely poor especially in patients over 60 years of age (15-20%). With ~20000 new cases in the US in 2015, poor prognosis following first remission and no other effective remission therapies currently available, AML represents an orphan indication with particularly high unmet need.

Ceplene® acts by enhancing the immunostimulatory effects of IL-2, a T-cell-derived cytokine responsible for activating multiple functions of anti-leukemic T and NK cells. The ability of T and K cells to recognize and eliminate leukemic cells determines the likelihood of maintaining CR in AML. These cells, however, are frequently dysfunctional in AML due to inhibition by myeloid-cell derived reactive oxygen species (ROS). By countering ROS-induced dysfunction and apoptosis of T and NK cells, Ceplene® induces immune-mediated killing of leukemic cells, providing a strong pharmacokinetic rationale for this combination therapy.

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A Phase III clinical study of 320 adult patients with acute AML in remission met its primary endpoint of increased leukemia-free survival (p <0.01), indicating that Ceplene® offers an efficacious and tolerable treatment in this population. The absence of treatment-related mortality, combined with the favorable safety profile of Ceplene®, represents a major improvement in the approach to remission maintenance therapy in AML patients. These clinically meaningful, significant results were published in Blood, a leading scientific journal in hematology, (Blood; The Journal of the American Society of Hematology, volume 108, number 1, pp. 88-96, July 1, 2006).

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Stage of Development

The European Commission has approved Ceplene® for the remission maintenance and prevention of relapse in adult patients with Acute Myeloid Leukemia in first remission. Ceplene® has been granted orphan drug status for the treatment of AML by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Additional clinical pharmacology and outcomes data in biomarker-defined sub-populations from a post-marketing study conducted in Europe are expected in Q1 2016.