How effective is Xenpozyme?

Xenpozyme (olipudase alfa-rpcp) is effective for the treatment of non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adults and pediatric patients. ASMD was previously called Niemann-Pick disease types A, A/B, and B.

ASMD is caused by a lack of acid sphingomyelinase (ASM), an enzyme that breaks down a fatty substance called sphingomyelin that is found in cells. If you lack enough functional ASM enzyme, sphingomyelin builds up and damages certain organs.

Overtime a build-up of sphingomyelin can cause a range of ASMD symptoms including:

• Reduced lung function
• Enlarged spleen and/or liver
• Reduced platelet numbers (thrombocytopenia)
• Delayed growth in children

Xenpozyme helps to decrease the storage of sphingomyelin, decrease the size of enlarged organs (organomegaly) and improve the function of the lungs and liver. It may also improve some other non-central nervous system symptoms of ASMD.

How effective is Xenpozyme in adults?

According to the results of a year-long study comparing Xenpozyme with placebo, which was conducted in 36 patients with ASMD, treatment with Xenpozyme:

• Improved lung function
  
  At the beginning of the study, the average level of lung function in both the Xenpozyme and placebo groups was a moderate level, according to diffusing capacity of the lungs for carbon monoxide (DLCO) test results (mean baseline percent predicted DLCO Xenpozyme: 49.4 ± 11.0 vs placebo: 48.5 ± 10.8). The test measures the ability of the lungs to transfer gas from the air breathed in into the bloodstream and is used to measure lung function.
  
  After 52 weeks’ treatment, the DLCO results were significantly improved in the Xenpozyme group compared with the placebo group (increase of 21.97% vs 2.96%, p = 0.0004). The percentage change from baseline in the Xenpozyme group ranged from 7 to 78% compared with -14 to 29% in the placebo group. Other tests conducted during the study also indicated that Xenpozyme improved lung function.
• Decreased spleen volume
  
  At the beginning of the study, the average spleen size in both the Xenpozyme and placebo groups was indicative of moderate to severe splenomegaly (enlarged spleen). After 52 weeks’ treatment, spleen sizes were significantly decreased in the Xenpozyme group compared with the placebo group (-39.4% vs 0.48%, p <0.0001). While spleen volumes in the placebo group were essentially unchanged over the course of the study, all but one of the patients in the Xenpozyme group saw their spleen volume decrease by more than 30%. The only patient who didn’t see such a reduction missed multiple treatments.
• Decreased liver volume
  
  Xenpozyme significantly reduced liver volumes compared with placebo (-28.1% vs 1.5%, p < 0.0001). At the beginning of the study, the average liver volume in both the Xenpozyme and placebo groups showed moderate hepatomegaly (enlarged liver). While liver volumes remained largely unchanged in the placebo group during the study, all patients treated with Xenpozyme had a reduction in the size of their liver, including 12 patients with moderately enlarged livers at the outset who only had a mild enlargement after 52 weeks of treatment.
• Increase platelet counts
  
  The average platelet count at the beginning of the study showed that patients in both the Xenpozyme and placebo groups were experiencing mild thrombocytopenia. Xenpozyme treatment increased platelet counts more than placebo did (16.82 vs 2.49 % change from baseline, respectively, p = 0.0185).

Following the year-long study, patients in the Xenpozyme and placebo groups were given the chance to remain in the study for up to 4 years and all patients were assigned to take Xenpozyme. After up to two years of treatment with Xenpozyme, results continued to show improvement in the outcomes mentioned above.

How effective is Xenpozyme in children?

According to the results of a year-long study comparing Xenpozyme with placebo, which was conducted in 20 patient with ASMD ranging in age from 1 to 17 years of age, treatment with Xenpozyme:

• Improved lung function
  
  At the beginning of the pediatric study, DLCO test results showed that of the nine pediatric patients who could undergo this testing, one had severely impaired lung function, four had moderately impaired lung function and four had mildly impaired lung function (mean baseline percent predicted DLCO was 54.8 ± 14.2 percent). Treatment with Xenpozyme significantly improved lung function with an average increase of 33 percent observed after a year of treatment (p = 0.0053).
  
  Treatment with Xenpozyme also improved interstitial lung disease (ILD) in pediatric patients. After 52 weeks of treatment there was a reduction in the ground glass appearance and/or reticulonodular density observed. Mean ILD scores also decreased. Five of the six patients with severe ILD at the beginning of the study, only had mild or moderate ILD at the end of the study and the other patient had no signs of ILD.
• Decreased spleen volume
  
  All patients in the pediatric study had moderate or severe enlargement of their spleen (splenomegaly) at the beginning of the study. Treatment with Xenpozyme resulted in spleen volume decreases ranging from -23 to -61 percent. The average decrease across all age groups was -49.2 ± 9.7 percent ( p < 0.0001). All but one of the 12 patients with severe enlargement of their spleen at the beginning of the study improved to a moderate level of enlargement by 52 weeks’ treatment.
• Decreased liver volume and improved liver function
  
  All patients in the pediatric study had moderate or severe enlargement of their liver (hepatomegaly) at the beginning of the study. Treatment with Xenpozyme resulted in liver volume decreases ranging from -17 to -61 percent. The average decrease across all age groups was -40.6 ± 9.4 percent (p < 0.0001). All of the 10 patients with severe liver enlargement at the beginning of the study improved to a moderate level of enlargement by 52 weeks’ of treatment.
  
  Treatment with Xenpozyme also returned liver enzyme levels back to normal in most of the patients who had elevated levels. Alanine transaminase (ALT) and aspartate transaminase (AST) levels were elevated in 80 percent of the patients at the start of the study, but after 52 weeks of treatment with Xenpozyme only 2 patients had abnormal AST levels and only 2 patients had abnormal ALT levels.
• Improve lipid profiles
  
  At the beginning of the pediatric study, lipid levels were generally above the normal range among the patients. Treatment with Xenpozyme resulted in improved cholesterol by 26 weeks and the average lipid level among the patients was within the normal range by week 52 of the study.
• Improved growth
  
  Improved growth was observed after 52 weeks of treatment with Xenpozyme in some of the pediatric patients enrolled in the study, as shown by the improvements observed in the mean height Z scores. After 52 weeks’ treatment, height Z scores improved in 79 percent of patients and remained the same in 21 percent. At the beginning of the studyl the median height Z score was -2.0 (range -3.8 to -1.0) and at the end of the trial the median score was -1.5 (range - 3.4 to -0.6). The average improvement was 0.56 (p < 0.0001).

A long-term trial in pediatric patients was ongoing in late 2022.

How quickly does Xenpozyme work?

Xenpozyme results in decreased levels of sphingomyelin during the first 26 weeks of treatment, according to the results of a clinical study. ASMD is caused by a build-up of this lipid.

In a study conducted in adults, significant improvement in lung function, spleen volume, liver volume and platelet counts were observed after 26 weeks of treatment with Xenpozyme. Significant improvements in lipid levels, spleen volume and liver volume were also observed after 26 weeks of treatment with Xenpozyme in a study conducted in pediatric patients.