Duvelisib

Published

dm+d

Unassigned

New Medicines

CopiktraRelapsed or refractory chronic lymphocytic leukaemia (CLL) after at least two prior therapies

Information

Copiktra
New molecular entity
Secura Bio
Secura Bio

Development and Regulatory status

Licensed but not launched
Approved (Licensed)
Launched
Yes
Mar 22Company has no plans to launch this product in the UK [19].
Nov 21This product is no longer an orphan medicine for this indication in the EU. It was originally designated an orphan medicine on 26 April 2013. The product was withdrawn from the Union Register of orphan medicinal products by the European Commission in March 2021 upon request of the marketing authorisation holder at the time of the granting of a marketing authorisation [17].
Sep 21Secura Bio enters into a distribution agreement for Copiktra with Clinigen covering 39 countries in Europe including Austria, Belgium, Croatia, Czech Republic, Denmark, Finland, France, Greece, Hungary, Ireland, Italy, The Netherlands, Poland, Portugal, Spain, Sweden and Switzerland. Secura Bio will promote and distribute Copiktra directly in Germany and the UK [18].
Jun 21Approved in EU [15].
May 21Approved by MHRA for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) after at least two prior therapies [16].
Mar 21Recommended for EU approval by CHMP - the full indication is "the treatment of adult patents with: Relapsed or refractory chronic lymphocytic leukaemia (CLL) after at least two prior therapies (see SmPC section 4.4. and 5.1); and Follicular lymphoma (FL) that is refractory to at least two prior systemic therapies (see SmPC section 4.4. and 5.1). It should be prescribed by physicians experienced in the treatment of cancer." [15].
Sep 20Secura Bio completes the acquisition of the global rights to duvelisib (Copiktra®) for all oncology indications from Verastem Oncology. Secura Bio will assume all operational and financial responsibility for activities that were previously part of the Verastem duvelisib program, including commercialisation efforts in the US and Europe. Verastem is entitled to receive low double-digit royalties on net sales over $US100 million in the US, Europe and the UK. Verastem will also receive 50% of licensing milestones (up to $US146 million) and royalties outside of US, Europe and the UK [13].
Jan 20Filed in EU for treatment of adult patients with relapsed or refractory CLL or SLL and relapsed or refractory follicular lymphoma (FL)[12].
Jul 19Verastem Europe GmbH, a wholly-owned subsidiary of Verastem, Inc., is registered in Munich, Germany. The company is currently pursuing regulatory approval for Copiktra in the EU and is evaluating potential commercialisation strategies [11].

Dec 18: No plans for licensing in Europe or for commercial agreements with other companies discussed in recent company SEC filings or listed in pipeline [10].


Sep 18: Launched in US [9].


Sep 18: Approved in the US with a monthly list price of $11,800, and expected to be available within a week. Duvelisib will carry a black-box warning of four potentially fatal toxicities—infections, diarrhoea or colitis, cutaneous reactions and pneumonitis [7,8].


Feb 18: NDA submitted to US FDA for treatment of relapsed/ refractory chronic lymphocytic/small lymphocytic lymphoma and accelerated approval for relapsed/ refractory follicular lymphoma [6].


Sept 17: based on the results of the DUO study (NCT02004522), Verastem intends to file a New Drug Application (NDA) for relapsed/refractory CLL/SLL in the first half of 2018 [5].


Nov 16: Infinity Pharmaceuticals has terminated its agreement with AbbVie and has granted exclusive worldwide rights for duvelisib to Verastem Pharmaceuticals [4].


Jan 17: NCT02004522 due to complete November 2017


Jan 17: NCT02049515 due to complete November 2018


Dec 15: NCT02004522 due to complete Nov 17 [3]


Mar 15: generic name assigned; orphan status for CLL EU/US; AbbVie to commercialise outside US [2].

Category

Inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma
CLL is the most common leukaemia in the Western world with an incidence of 4.2 per 100,000 a year. The incidence increases to more than 30 per 100,000 a year at an age of >80 years. The median age at diagnosis is 72 years. About 10% of CLL patients are reported to be younger than 55 years
Relapsed or refractory chronic lymphocytic leukaemia (CLL) after at least two prior therapies
Oral

Further information

Yes

Trial or other data

Sep 17Verastem announces that duvelisib achieved its primary endpoints in the DUO trial vs. ofatumumab; patients taking duvelisib had a statistically significant improvement in progression free survival (median 13.3 months vs. 9.9 months) [5].
Feb 14NCT02049515 is a PIII study of IPI-145 or ofatumumab in 150 patients with Chronic Lymphocytic Leukaemia/ Small Lymphocytic Lymphoma previously enrolled in study IPI-145-07. The study is designed to enable subjects who experience radiologic disease progression in the core study to receive the alternative treatment (either IPI-145 or ofatumumab). Subjects who have previously received ofatumumab will receive a starting dose of 25mg IPI-145 twice daily for 21 days of a 28 day cycle for up to 12 cycles. The primary outcome is overall response rate. The study starts Dec 13 and is due to complete Dec 19. [1]
Feb 14NCT02004522 (DUO) is a PIII study of IPI-145 vs ofatumumab in 300 patients with relapsed or refractory chronic lymphocytic leukaemia/ small lymphocytic lymphoma. The primary outcome is progression free survival. The study starts Nov 13 and is due to complete Dec 17 (primary data collection Aug 15) [1].

Evidence based evaluations

CopiktraFollicular lymphoma (FL) refractory to at least two prior systemic therapies

Information

Copiktra
New molecular entity
Secura Bio
Secura Bio

Development and Regulatory status

Licensed but not launched
Approved (Licensed)
Launched
Yes
Mar 22Company has no plans to launch this product in the UK [22].
Nov 21This product is no longer an orphan medicine for this indication in the EU. It was originally designated an orphan medicine on 17 July 2013. The product was withdrawn from the Union Register of orphan medicinal products by the European Commission in March 2021 upon request of the marketing authorisation holder at the time of the granting of a marketing authorisation [19].
Sep 21Secura Bio enters into a distribution agreement for Copiktra with Clinigen covering 39 countries in Europe including Austria, Belgium, Croatia, Czech Republic, Denmark, Finland, France, Greece, Hungary, Ireland, Italy, The Netherlands, Poland, Portugal, Spain, Sweden and Switzerland. Secura Bio will promote and distribute Copiktra directly in Germany and the UK [21].
Jun 21NICE appraisal was suspended in April because the company was unable to provide an evidence submission [18].
Jun 21Approved in EU [16].
May 21Approved by MHRA for Follicular lymphoma (FL) that is refractory to at least two prior systemic therapies [17].
Mar 21Recommended for EU approval by CHMP - the full indication is "the treatment of adult patents with: Relapsed or refractory chronic lymphocytic leukaemia (CLL) after at least two prior therapies (see SmPC section 4.4. and 5.1); and Follicular lymphoma (FL) that is refractory to at least two prior systemic therapies (see SmPC section 4.4. and 5.1). It should be prescribed by physicians experienced in the treatment of cancer." [15].
Sep 20Secura Bio completes the acquisition of the global rights to duvelisib (Copiktra®) for all oncology indications from Verastem Oncology. Secura Bio will assume all operational and financial responsibility for activities that were previously part of the Verastem duvelisib program, including commercialisation efforts in the US and Europe. Verastem is entitled to receive low double-digit royalties on net sales over $US100 million in the US, Europe and the UK. Verastem will also receive 50% of licensing milestones (up to $US146 million) and royalties outside of US, Europe and the UK [14].
Jan 20Filed in EU for treatment of adult patients with relapsed or refractory CLL or SLL and relapsed or refractory FL [13].
Jul 19Verastem Europe GmbH, a wholly-owned subsidiary of Verastem, Inc., is registered in Munich, Germany. The company is currently pursuing regulatory approval for Copiktra in the EU and is evaluating potential commercialisation strategies [12].

Dec 18: No plans for licensing in Europe or for commercial agreements with other companies discussed in recent company SEC filings or listed in pipeline [11].


Sep 18: Launched in US [10].


Sep 18: Accelerated approval granted in the US for the treatment of adult patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies. Approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [9].


Apr 18: Filed with the FDA with priority review seeking accelerated approval for the treatment of relapsed or refractory follicular lymphoma. Decision expected in Oct 2018 [8].


Sept 17: Verastem may seek US authorisation for both NHL and CLL/SLL together - they have announced that the New Drug Application for CLL/SLL is expected to include the data from the DYNAMO study in NHL [7].


Nov 16: Infinity Pharmaceuticals has terminated its agreement with AbbVie and has granted exclusive worldwide rights for duvelisib to Verastem Pharmaceuticals [6].


Jun 16: In light of DYNAMO study results, Infinity plans to seek feedback from the FDA to determine next steps with respect to duvelisib in indolent NHL [5].

Category

A small-molecule, selective dual inhibitor of phosphatidylinositol 3 kinase (PI3K) δ and γ isoforms. The PI3K pathway promotes cell proliferation, growth, motility, metabolism and survival.
Indolent NHLs include follicular lymphomas, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, small lymphocytic lymphoma and marginal zone lymphoma. Follicular lymphoma is the second most common subtype of NHL [1]. In 2013-14, there were 22,015 admissions for follicular lymphoma (ICD-10 C82) in England, resulting in 14,046 bed days and 22,551 finished consultant episodes [2]
Follicular lymphoma (FL) refractory to at least two prior systemic therapies
Oral

Further information

Yes

Trial or other data

Jun 16Infinity announces duvelisib hit the primary endpoint in the PII DYNAMO study but fell short of expectations, with an overall response rate of 46% in the study, all partial. AbbVie and Infinity are to pause an AbbVie-run PIb/II study pairing duvelisib with venetoclax as they explore next steps. Infinity had hoped duvelisib as a monotherapy would have provided a larger clinical benefit [5].
Oct 15The 120th pt enrolled into the PII DYNAMO study. Infinity expect to report topline data from DYNAMO in Q3 of 2016 [4].
Sep 15NCT01882803 = DYNAMO [3].
May 13PII (NCT01882803) study starts. It will evaluate the safety and efficacy of IPI-145 as a monotherapy in 120 pts with iNHL (Follicular Lymphoma, Marginal Zone Lymphoma, or Small Lymphocytic Lymphoma) that is refractory to rituximab and to either chemotherapy or RIT, recruited from sites in the US, EU (including UK), Canada & Belarus. Collection of primary outcome data (overall response rate) should complete in Dec 17 [3].

Evidence based evaluations