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Articles

Safety in Lactation: Antimetabolites

23 September 2020Antineoplastic antimetabolites, whether used as monotherapy or in combination with other antineoplastics, are contra-indicated in breastfeeding (except where indicated below) because of their effects on…

Azacitidine: Cytotoxic Drug Stability Monograph

1 September 2020Stability information is essential for the safe aseptic preparation of azacitidine
Search Articles

Lactation Safety Information

No
No published evidence of safety
Serious adverse effects reported in adults
24 September 2020

New Medicines

OnuregAcute myeloid leukaemia (AML), post-induction maintenance - oral formulation

Information

Onureg
New formulation and new indication
Bristol-Myers Squibb
Celgene

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Launched
Yes
Nov 21This product no longer has orphan drug status in the EU. The designation (EU/3/07/509) was withdrawn from the Community register of orphan medicinal products in Dec 18 at the end of the 10-year period of market exclusivity [19].
Aug 21The licensed indication in the UK is use as maintenance therapy in adult patients with acute myeloid leukaemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT) [18].
Aug 21Approved by MHRA for post-induction maintenance of AML in adults [18].
Jun 21Approved in EU [17].
Apr 21Recommended for EU approval by CHMP - the full indication is "as maintenance therapy in adult patients with acute myeloid leukaemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT)." Onureg will be available as 200 mg and 300 mg film-coated tablets [16].
Dec 20Onureg is licensed in the US for the continued treatment of adult patients with AML who achieved first complete remission (CR) or CR with incomplete blood count recovery (CRi) following intensive induction chemotherapy and who are not able to complete intensive curative therapy [12].
Nov 20Since its launch in the US, Onureg generated $3 million in the third quarter. Commentators note that BMS has its work cut out, as the market is largely underdeveloped because there were previously no approved drugs in the setting. But the company message is thought to be resonating well so far [14].
Sep 20Approved in US [11].
Jun 20Filed in EU via centralised procedure [10].
May 20The FDA granted the application Priority Review and set a Prescription Drug User Fee Act (PDUFA) goal date of September 3, 2020 [9].
May 20The FDA has accepted a New Drug Application for azacitidine for the maintenance treatment of adult patients with acute myeloid leukemia who achieved complete remission (CR) or CR with incomplete blood count recovery following induction therapy with or without consolidation treatment and who are not undergoing bone marrow transplant [8].
Mar 20Has orphan drug status in US & EU for AML [7].
Jul 16PIII trials start [1].

Category

A nucleoside analogue of cytidine that specifically reduces DNA methylation by inhibition of DNA methyltransferase.
AML is the most common malignant myeloid disorder in adults. The incidence of AML is slightly higher in males than in females, and it also increases with age. In 2011, 2,254 cases of AML were reported in England (representing 3.1 cases per 100,000 population). In England and Wales, 2,245 deaths from AML were registered in 2012 (ICD-10 C92.0).
Acute myeloid leukaemia (AML), post-induction maintenance - oral formulation
Oral

Further information

Yes

Trial or other data

Jan 21PIII QUAZAR AML-001 RCT (n=472) found oral azacitidine provided a significantly increased overall survival and relapse free survival vs placebo (24.7 months vs 14.8 months, and 10.2 months vs 4.8 months respectively, p<0.001 for both). Neutropenia was more common with azacitidine (41% vs 24%) [15].
Sep 19PIII trial of maintenance treatment with CC-486 in QUAZAR AML-001 (NCT01757535) in 472 patients resulted in a highly statistically significant and clinically meaningful improvement in overall survival compared to placebo [6].
Jan 19NCT01757535 has competed recruitment but is ongoing Estimated date for primary completion Jan 19 and for study completion Apr 19 [5].
Dec 17NCT01757535 primary data now due Jan 19 [4]
Aug 16PIII trial to assess the efficacy and tolerability of oral azacitidine, plus best supportive care, as maintenance therapy in patients with AML in complete remission (QUAZAR AML-001; NCT01757535) is currently recruiting 460 patients with de novo AML or AML secondary to a previous diagnosis of MDS. Enrolment is underway in the US, Canada, Australia, South Korea, Belgium, Germany, Austria, Italy, Portugal, Lithuania, Spain, Finland, Czech Republic and Israel. Collection of primary outcome data (overall survival) is due to complete Sep 18 [3].
Aug 14Single-arm PII trial to assess efficacy of azacitidine as maintenance treatment in elderly patients with AML in complete remission after induction chemotherapy (NCT00387647) completes. The primary endpoint was the rate of disease-free survival at 1 year. The trial enrolled 24 patients aged 60 years and over [2].

Evidence based evaluations

OnuregRelapsed or refractory angioimmunoblastic T-cell lymphoma (AITL)

Information

Onureg
Licence extension / variation
Bristol-Myers Squibb
Celgene

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

A nucleoside analogue of cytidine that specifically reduces DNA methylation by inhibition of DNA methyltransferase.
A mature T-cell non-Hodgkin lymphoma, characterised by systemic disease and a polymorphous infiltrate involving lymph nodes and extranodal sites. The clinical course is typically aggressive [1].
Relapsed or refractory angioimmunoblastic T-cell lymphoma (AITL)
Oral

Further information

Yes

Evidence based evaluations

OnuregMyelodysplastic syndromes (MDS), lower risk - oral formulation

Information

Onureg
Licence extension / variation
Bristol-Myers Squibb
Celgene

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes

Category

A nucleoside analogue of cytidine that specifically reduces DNA methylation by inhibition of DNA methyltransferase.
Annual incidence of MDS is estimated at 4 per 100,000, but many cases remain undiagnosed.
Myelodysplastic syndromes (MDS), lower risk - oral formulation
Oral