dm+d

Unassigned

New Medicines

XenpozymeAcid sphingomyelinase deficiency (previously known as Niemann-Pick disease, type A/B or B) in adults and children

Information

Xenpozyme
New molecular entity
Genzyme
Genzyme

Development and Regulatory status

Phase III Clinical Trials
Approved (Licensed)
Pre-registration (Filed)
Yes
Yes
Jun 22Approved in the EU [15].
May 22Recommended for EU approval by CHMP as “as an enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in paediatric and adult patients with type A/B or type B.” Xenpozyme will be available as a 20mg powder to be reconstituted into a concentrate for solution for infusion [14].
Oct 21Submissions have been made for olipudase - presumably to EMA and FDA [11].
Apr 20Filings now anticipated 2021 [10].
Jan 20Sanofi announce plans to begin global regulatory submissions in H2 2021.[8]
Mar 18Filings planned for 2020 [6].
Jan 17Still listed as active at PIII in Sanofi-Genzyme pipeline [5].
Dec 15P2/3 trial (NCT02004691) initiated: an open-label study designed to compare the safety, efficacy and pharmacokinetics of three different doses of olipudase (0.3, 1.0 and 3.0 mg/kg) in NPB, administered by IV infusion once every two weeks for 52 weeks. Recruitment of approximately 35 subjects is underway in Germany, Italy, France and the United Kingdom [4].
Jun 15The FDA granted breakthrough status based on PIb data from 5 patients showing early signs of efficacy for the therapy. There are no approved treatments for NPB [1].
Jun 15Granted breakthrough therapy designation in the US [1].
Jun 15Olipudase alfa was granted orphan drug status for Niemann-Pick diseases in the US in August 2000, and in Europe in 2001 [2].

Category

Recombinant human acid sphingomyelinase (rhASM) enzyme replacement therapy
Niemann-Pick disease, type B affects less than 0.04 in 10,000 people in the EU (equivalent to 1 in 250,000 people or 200-250 people in England) [3].
Acid sphingomyelinase deficiency (previously known as Niemann-Pick disease, type A/B or B) in adults and children
Intravenous infusion

Further information

Yes

Trial or other data

Jan 20Positive topline results from PII/III ASCEND trial (NCT02004691, n=36 pts in 24 centres in 16 countries) of olipudase alfa for treatment of ASMD (Nieman-Pick disease). Pts received olipudase alfa i.v. (up to 3mg/kg) or placebo every 2 weeks over the course of a year. The trial had two independent primary efficacy endpoints; progressive lung disease and enlarged spleen. The improvement in lung function endpoint was met with a 22% improvement to week 52 vs. 3% with placebo arm. The other primary endpoint, spleen size, was also met; spleen volume decreased by 39.5% with olipudase alfa vs. 0.5% with placebo. [8,9]
Oct 19Pivotal trial (NCT02004691) has completed primary outcomes [ClinicalTrials.gov] and Sanofi expect data read-out in Q1 2020 [7].
Apr 15Genzyme initiates a PI/II trial to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of escalating doses of olipudase alfa in paediatric patients with acid sphingomyelinase deficiency (DFI13803; U1111-1160-6469; NCT02292654). The trial is intended to enrol 12 patients, aged 17 years and younger, in the US [2].
Feb 15Results from the PIb study showed that IV olipudase alfa was well tolerated at doses (q2w) increasing from 0.1 mg/kg to 3.0 mg/kg. No serious adverse events or deaths occurred in the five enrolled patients during the 26-week study, and all patients reached the maximum administered dosage of 3 mg/kg [2].
Feb 15Genzyme plans to initiate a PII/III study of olipudase alfa in adults with Niemann-Pick Type B (NCT02004691) in 2H 2015 [1].
Jan 14Recruitment of 15 pts begins to a PII trial to evaluate olipudase alfa (DFI12712; NCT02004691). The open-label study has been designed to compare the safety, efficacy and pharmacokinetics of three different doses of the agent (0.3, 1.0 and 3.0 mg/kg) administered by IV infusion once every two weeks for 52 weeks [2].
Dec 13Genzyme initiates an open-label, PII long-term study to evaluate the safety and efficacy of olipudase alfa in patients with Niemann-Pick disease type B who have completed the treatment period of a previous study of olipudase alfa (LTS13632; NCT02004704). Primary endpoints, relating to safety and the incidence of adverse events, will be assessed for up to 5 years. The trial is recruiting approximately 70 pts in the US [2].