dm+d

Unassigned

New Medicines

BrukinsaWaldenström’s macroglobulinemia (WM)

Information

Brukinsa
New molecular entity
BeiGene
BeiGene

Development and Regulatory status

Phase III Clinical Trials
Recommended for approval (Positive opinion)
Launched
Yes
Yes
Sep 21Recommended for EU approval by CHMP “for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy”. Brukinsa will be available as 80mg hard capsules [14].
Sep 21Approved in US [13].
Feb 21US FDA accept sNDA for treatment of Waldenstroms macroglobulinaemia [12].
Jun 20Has orphan drug status in EU (EU/3/19/2167) for treatment of lymphoplasmatic lymphoma. WM is the most common type of lymphoplasmatic lymphoma [10].
Jun 20Filed in EU [9].
Nov 19Beigene plans to file a sNDA in the US in early 2020 [8].
Nov 19Beigene has commercial teams in China and the US. In the EU, it is evaluating its commercialisation strategy including potential collaborations [8].
Jul 18Granted Fast Track designation by the US FDA. Company announce plans to submit a New Drug Application in the H1 2019 [5].
Jan 17BeiGene announces that it will start a global PIII trial in WM, for which the drug has Orphan Status in the US; the trial will compare BGB3111 to ibrutinib as the company believe it will have a better adverse effect profile due to greater selectivity [1].

Category

Brutons tyrosine kinase (BTK) inhibitor
WM is a rare chronic B-cell lymphoproliferative disorder, classed as a low-grade NHL. Age-standardised annual UK incidence is 0.55 per 100,000 with male predominance. Median age at presentation is 71 years & median overall survival is 60 months; there is an association with multiple auto-immune disorders. A significant minority of pts remain asymptomatic & never require therapy while others have advanced lymphoma requiring therapy.
Waldenström’s macroglobulinemia (WM)
Oral

Further information

Yes

Trial or other data

Apr 20PIII ASPEN continues to follow-up recruited patients [11].
Dec 19Results from cohort 1 of PIII ASPEN trial (median follow-up of 19.4 months) announced. In the overall pt population, the VGPR rate was 28.4% in the zanubrutinib arm vs. 19.2% in the ibrutinib arm (p=0.0921) with no pts achieving a CR in either arm. While the trial was not powered to detect a statistically significant improvement in progression free survival (PFS), the 12-month PFS rate was 89.7% in all pts in the zanubrutinib arm vs. 87.2% in the ibrutinib arm. The 12-month OS rate was 97% for all pts in the zanubrutinib arm vs. 93.9% in the ibrutinib arm. Grade >3 adverse events (AEs) were 58.4% in the zanubrutinib arm and 63.3% in the ibrutinib arm (atrial fibrillation/flutter; 2% vs. 15.3% with zanubrtinimab vs. ibrutinib, minor bleeding 48.5% vs. 59.2%, major haemorrhage; 5.9% vs. 9.2%, diarrhea; 20.8% vs. 31.6% and neutropenia; 29.7% vs. 13.3%. [7]
Jan 19NCT03053440 is ongoing but fully recruited. Estimated date for primary and study completion is Jun 21 [6]
Jan 17PIII trial started comparing zanubrutinib with ibrutinib (NCT03053440). The first cohort of approximately 150 patients with MYD88 mutations will be enrolled while the patients with MYD88 wildtype status will be enrolled in a second cohort and will receive zanubrutinib 160mg BID until progression. Primary completion date Jun 2021 [3,4]

Evidence based evaluations

Mantle cell lymphoma (MCL) - first-line with rituximb

Information

Licence extension / variation
BeiGene
BeiGene

Development and Regulatory status

None
Phase III Clinical Trials
Launched
Yes
Nov 19Launched in the US [4].
Nov 19Zanubrutinib receives accelerated approval in US for MCL, contingent upon verification and description of clinical benefit in a confirmatory trial [4].
Aug 19Filed in the US [4].
Jan 19Has orphan drug status in US [4].
Jan 19FDA awards zanubrutinib Breakthrough Therapy designation [1].

Category

Small molecule inhibitor of Bruton’s tyrosine kinase (BTK).
MCL is a rare, aggressive type of non-Hodgkin lymphoma that mostly affects men over the age of 60. There are about 3,000 to 4,000 new diagnoses in the U.S. each year [1].
Mantle cell lymphoma (MCL) - first-line with rituximb
Oral

Trial or other data

Dec 19PIII trial (NCT04002297) has a primary completion date of July 2021 [2].
Nov 19Results from a single arm, PII trial (NCT03206970) of Brukinsa (n=86) with mantle cell lymphoma who have received at least one prior treatment demonstrated that 84% of patients had tumour shrinkage, with a median duration of response of 19.5 months. Common side effects were decreased neutrophils and platelets, upper respiratory tract infection, decreased white blood cell count, decreased haemoglobin, rash, bruising, diarrhoea and cough [2,3].

BrukinsaChronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL); relapsed or refractory

Information

Brukinsa
Licence extension / variation
BeiGene
BeiGene

Development and Regulatory status

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

Category

Brutons tyrosine kinase (BTK) inhibitor
CLL/SLL is the most common leukaemia in the Western world with an incidence of 4.2/100,000/year. Incidence increases to >30/100,000/year at an age of >80 years [1].
Chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL); relapsed or refractory
Oral

BrukinsaRelapsed or refractory marginal zone B-cell lymphoma

Information

Brukinsa
Licence extension / variation
BeiGene
BeiGene

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Launched
Sep 21Zanubrutinib receives accelerated approval from the US FDA for the treatment of adults with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen. Approval is based on overall response rate (ORR) from two single-arm clinical trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.[2]

Category

BTK inhibitor
There are around 14,100 new non-Hodgkin lymphoma cases in the UK every year [1]. Marginal zone lymphomas (MZLs) account for between 5% and 17% of all NHL. MZLs consist of 3 different subtypes with extranodal being the most commonly reported, representing 50-70% of MZL, followed by splenic (20%) and nodal (10%) [1].
Relapsed or refractory marginal zone B-cell lymphoma
Oral

Trial or other data

Jun 21In the multicentre, pivotal PII MAGNOLIA trial (NCT03846427) in 66 pts who received >1 anti-CD20-based regimen (n=26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, 4 with unknown subtype). Based on CT scan assessment, the ORR was 56% (95% CI: 43, 68) with a complete response (CR) rate of 20%; based on PET-CT scan assessment, the ORR was 67% (95% CI: 54, 78) with a CR rate of 26%. The median duration of response (DoR) was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months (95% CI: 67, 93). Responses were observed in all MZL subtypes. [2-4]
Jun 20In the global PI/II trial of BGB-3111-AU-003 (NCT02343120), 20 pts (9 with extranodal subtype, 5 with nodal subtype, and 6 with splenic subtype) were assessed using CT scan. The ORR was 80% (95% CI: 56, 94) with a CR rate of 20%. The median DoR was not reached at the median follow-up time of 31.4 months, with 72% of responders still in remission at 12 months (95% CI: 40, 88). [5,6]

BrukinsaChronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL); first-line

Information

Brukinsa
Licence extension / variation
BeiGene
BeiGene

Development and Regulatory status

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

Category

Selective next-generation Bruton tyrosine kinase inhibitor
CLL is the most common form of leukaemia in adults, with a global incidence of approximately 114,000 new cases in 2017. SLL shares many similarities to CLL but with cancer cells found mostly in lymph nodes. The incidence of del(17p) is approximately 5% to 8% of patients with CLL at diagnosis and increases with each relapse [3,4].
Chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL); first-line
Oral