XenpozymeAcid sphingomyelinase deficiency (previously known as Niemann-Pick disease, type A/B or B) in adults and children
New molecular entity
Development and Regulatory status
Aug 22Approved in the US to treat children and adults with acid sphingomyelinase deficiency. There are fewer than 120 people diagnosed with ASMD in the US, with roughly two-thirds being children .
Aug 22Approved in UK as ´enzyme replacement therapy for the treatment of non-central nervous system (CNS) manifestations of acid sphingomyelinase deficiency in paediatric and adult patients with type A/B or type B´ .
Jun 22Approved in the EU .
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 .
Oct 21Submissions have been made for olipudase - presumably to EMA and FDA .
Apr 20Filings now anticipated 2021 .
Jan 20Sanofi announce plans to begin global regulatory submissions in H2 2021.
Mar 18Filings planned for 2020 .
Jan 17Still listed as active at PIII in Sanofi-Genzyme pipeline .
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 .
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 .
Jun 15Granted breakthrough therapy designation in the US .
Jun 15Olipudase alfa was granted orphan drug status for Niemann-Pick diseases in the US in August 2000, and in Europe in 2001 .
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) .
Acid sphingomyelinase deficiency (previously known as Niemann-Pick disease, type A/B or B) in adults and children
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 .
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 .
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 .
Feb 15Genzyme plans to initiate a PII/III study of olipudase alfa in adults with Niemann-Pick Type B (NCT02004691) in 2H 2015 .
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 .
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 .