Iclusig: new protein kinase inhibitor for leukaemia

Iclusig (ponatinib) is a protein kinase inhibitor that is licensed for the treatment of chronic myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) when certain other protein kinase inhibitors are unsuitable and in patients with the T315I resistance mutation.

Iclusig (ponatinib) is given at a dose of 45mg daily but this may be reduced or interrupted if toxicity occurs
Iclusig (ponatinib) is given at a dose of 45mg daily but this may be reduced or interrupted if toxicity occurs

PHARMACOLOGY

Ponatinib is a Brc-Abl kinase inhibitor that is especially effective against leukaemias resistant to other protein kinase inhibitors and those with the T315I resistance mutation.1

CLINICAL STUDIES

The pivotal phase II, open-label, single-arm PACE trial evaluated oral ponatinib (45mg once daily) in 449 patients with CML or Ph+ ALL. Patients were eligible for enrolment if they were resistant or intolerant to dasatinib or nilotinib or if they had a confirmed T315I mutation.2  

Primary endpoints were major cytogenic response for chronic phase CML and major haematologic response for ALL or acute or blast phase CML.2

Clinically meaningful responses

In the analysis at 12 months (median 14.5 months), there were clinically meaningful responses to ponatinib in all stages of leukaemia.2

Overall, 54% of patients with chronic phase CML and 70% of patients with the T315I mutation achieved a major cytogenetic response. Among patients with advanced CML, 58% of those with accelerated phase disease and 31% of those with blast phase disease acheived a major haematologic response. The Ph+ ALL group showed a major haematologic response rate of 41%.1

The most commonly reported adverse effects were blood dyscrasias (particularly thrombocytopenia) and skin disorders.1

Monitor for pancreatitis

Pancreatitis occurs in around 5% of patients receiving ponatinib; serum lipase should therefore be monitored every 2 weeks for the first 2 months and periodically thereafter. If raised lipase is accompanied by abdominal pain, treatment should be withheld and the patient should be evaluated for pancreatitis.1

References:

  1. Iclusig Summary of Product of Characteristics, July 2013.
  2. Cortes JE et al. Oral Presentation at American Society of Hematology Annual Meeting and Exposition, Atlanta, USA, December 2012. Abstract 163.

View Iclusig drug record

Further information: Ariad

Follow MIMS on Twitter

Want news like this straight to your inbox?
Sign up for our bulletins

Have you registered with us yet?

Register now to enjoy more articles and free email bulletins

Register
Already registered?
Sign in

Register or Subscribe to MIMS

GPs can get MIMS print & online and GPonline for free when they register online – take 2 minutes, and make sure you get your free MIMS access! If you're not a GP, you can subscribe to MIMS for full access.

Register or subscribe

MIMS Dermatology

Read the latest issue online exclusively on MIMS Learning.

Read MIMS Dermatology

MIMS Adviser

Especially created for prescribing influencers.

Request free copy

Mobile apps

MIMS: access the full drug database and quick-reference tables on the go

MIMS Diagnosis and Management: concise information on signs and symptoms, investigations and diseases