Monica Kumar's research while affiliated with Sanofi and other places

... The recombinant enzyme has a molecular weight of ≈ 75 kDa [13] and is not expected to cross the blood-brain barrier [19]; therefore, it has no clinical activity against CNS manifestations of ASMD. The pharmacodynamic activity of olipudase alfa was initially assessed in five adults with ASMD in a phase 1b trial [17,20] and its long-term extension over up to 6.5 years [21][22][23]. Discussion in this section focuses mainly on larger clinical trials conducted in adult [24] and paediatric [25] patients with ASMD type A/B or B. Lyso-sphingomyelin (a deacylated form of sphingomyelin) and chitotriosidase (an enzyme produced by activated macrophages) levels are elevated in patients with ASMD and they serve as pharmacodynamic biomarkers of response to olipudase alfa [24,25]. Olipudase alfa treatment for 52 weeks was associated with a substantial reduction from baseline in mean pre-infusion plasma lyso-sphingomyelin levels (− 78% vs − 6.1% with placebo in adult patients [24]; − 87% in paediatric patients [15,25]) and mean plasma chitotriosidase levels (− 54.7% vs − 12.3% with placebo in adult patients, nominal p = 0.0003 [24]; − 58% in paediatric patients [25]). ...

... Some of the clinical features that NPB patients present are as follows: 1. Hepatic involvement that can be severe and evolve into chronic hepatitis and fibrosis; sometimes, there are cases of fulminant hepatitis in adulthood. Some patients present portal hypertension or elevation of transaminases and bilirubin [13]; 2. Hemograms of patients may show decreased platelets, hemoglobin, and leukocytes, many of them with thrombocytopenia, which causes bleeding episodes, petechiae, and ecchymosis [14]; 3. Pulmonary involvement due to the accumulation of lipid-laden macrophages in the alveolar septa of the bronchial walls and pleura. Pulmonary lavage is used to prevent lipid deposition and is not very effective; 4. They may present growth problems with delayed skeletal maturation (low weight and height), presenting in some cases with osteopenia Some of the clinical features that NPB patients present are as follows: 1. Hepatic involvement that can be severe and evolve into chronic hepatitis and fibrosis; sometimes, there are cases of fulminant hepatitis in adulthood. ...

... Míg az NPD-C-típusú betegek számára elérhető a betegségspecifikus terápia, addig a B-típusú pácienseknél egészen az elmúlt pár évig csak tüneti kezelés (koleszterinszintet csökkentő gyógyszerek) volt alkalmazható. Az utóbbi években számos klinikai vizsgálat indult enzimpótló terápiával (ERT = enzyme replacement therapy) gyermekek és felnőttek kezelésére is, melyek eredményei biztatóak [22][23][24][25][26]. ...

... In a phase 2/3 trial, the mean percent change from baseline at 52 week was − 92.7% in olipudase alfa recipients, compared with + 10.9% in placebo recipients [24]. Liver sphingomyelin clearance during olipudase alfa treatment was associated with improved lipid profiles [22,24,27]. ...

... Two separate clinical studies evaluating olipudase alfa for the treatment of chronic ASMD in adult and paediatric patients have also demonstrated positive results [27,31]. The Phase I/II open label, ascending dose, multicentre ASCEND-Peds study (NCT02292654) evaluated the safety, tolerability, and pharmacokinetics of olipudase alfa in 20 paediatric patients with chronic visceral ASMD over a 64-week study period [27]. ...

... Of note, olipudase alfa is the first and only investigational ERT in late-stage development for ASMD. Olipudase alfa acts by targeting the underlying metabolic defect by supplementing the deficient enzyme activity [24]. ...