Date: 2014-03-26
Type of information:
phase: 3
Announcement: results
Company: Swedish Orphan Biovitrum - SOBI (Sweden)
Product: Kiobrina® (recombinant produced human bile-salt stimulated lipase)
Action mechanism:
Disease: treatment of preterm infants
Therapeutic area:
Country: 11 European countries
Trial details: The phase III study is a multicenter, double- blind, placebo-controlled study where preterm infants younger than 32 weeks of gestational age are randomized to receive Kiobrina® or placebo added to preterm formula or pasteurized human milk for 4 weeks to demonstrate improved growth velocity. After treatment, there is a follow up period of 1 year. The trial is expected to enroll patients in 70 centers in 11 European countries.
Latest
news: * On March 26, 2014, Swedish Orphan Biovitrum (Sobi) has announced topline data from the company's pivotal phase 3 study of its enzyme therapy Kiobrina (rhBSSL - recombinant human Bile Salt Stimulated Lipase). The primary endpoint of the study - growth velocity measured after four weeks of treatment with rhBSSL - was not met. No statistically significant improvement in growth velocity was demonstrated in preterm infants treated with rhBSSL compared to placebo. Topline results from the multi-centre phase 3 European trial of rhBSSL, called the LAIF study (Lipase Added to Infant Feeding), showed that in 410 infants born before 32 weeks of gestational age, the mean growth velocity did not differ when treated with rhBSSL (16.8 g/kg/day) compared to placebo (16.6 g/kg/day). The estimated difference in growth velocity was 0.21 g/kg/day (95% CI (-0.40; 0.83), p=0.49). The growth velocity was comparable between groups throughout the treatment period, and the median enteral feeding volume was 2.7 mL/kg/day lower in the rhBSSL group. Ninety-eight per cent of infants completed the four week treatment period.The study also included several secondary endpoints. No significant differences between the rhBSSL and placebo groups were observed in the initial analysis of head circumference (3.92 cm compared to 3.88 cm; 95% CI (-0.15; 0.24), p=0.66) and readiness for hospital discharge (45.1 compared to 45.2 days; 95% CI (-3.2; 2.9) p=0.93).A higher incidence of adverse events was observed during the four weeks treatment period in the rhBSSL treated infants, with signs of gastrointestinal intolerance and potential cases of necrotising enterocolitis (NEC). Further investigation is required to better understand these findings. Although the overall result was negative, infants small for gestational age (SGA) (n=62), demonstrated higher growth velocity compared to placebo (17.1 g/kg/day vs. 15.1 g/kg/day, with an estimated difference of 1.95; 95% CI (0.38; 3.52)). SGA babies have a birthweight below the tenth percentile for gestational age, and were a pre-specified subgroup. Further analysis is required to determine the relevance of this finding. The company has also announced that these results do not support initiation of the US trial.* On November 5, 2013, Swedish Orphan Biovitrum (Sobi) has explained that the top line data will initially include the primary endpoint of growth velocity at four weeks as well as some secondary endpoints from the period of the preterm infants' hospitalization. The company reiterated its expectation that the top line data for the study will be available in the first quarter in 2014.* On August 2, 2011, the first patient has been enrolled in the phase III study with Kiobrina® which is designed to evaluate efficacy, safety and tolerability of Kiobrina® in the treatment of preterm infants. Kiobrina® has been developed to improve growth in preterm infants who receive pasteurized breast milk or infant formula. The rationale for adding rhBSSL to pasteurized breast milk or infant formula is to restore the natural lipase activity level that is either lost in pasteurization of breast milk or totally absent in formula and thereby improve growth velocity in preterm infants.
The objective of this phase III study is to confirm the results from two previous phase II studies with Kiobrina® (rhBSSL) administered to either formula or pasteurized milk, respectively. The combined results from the phase II studies showed a statistically significant increase in growth velocity and uptake of long chain polyunsaturated fatty acids such as DHA (Docosahexanoic acid) and AA (Arachidonic acid) (omega-3 and omega-6 fatty acids).
