New Phase 3 Data at WCPGHAN Show Long-Term Safety, Tolerability, and Treatment Benefits of Bylvay (odevixibat) in PFIC

Albireo Pharma, Inc. (Nasdaq: ALBO), a clinical-stage rare liver disease company developing novel bile acid modulators, today presented clinical data from its Phase 3 PEDFIC 1 study and an interim data cut of the PEDFIC 2 long-term extension study of its lead product candidate, Bylvay (odevixibat). Data being shared at the 6th World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition (WCPGHAN) Meeting on June 2 - 5 shows that long-term treatment (up to 48 weeks) was associated with clinically meaningful, positive effects on cholestasis, growth, and sleep parameters in patients with progressive familial intrahepatic cholestasis (PFIC). The totality of the data supports the potential of Bylvay to provide benefits to patients with PFIC. Bylvay is a potent, once-daily, non-systemic ileal bile acid transport inhibitor (IBATi) currently being developed for the treatment of PFIC, biliary atresia, and Alagille syndrome.

"The data being presented at WCPGHAN showed consistent long-term safety and tolerability across studies, treatment groups, and doses and long-term treatment benefits of Bylvay in children with PFIC," said Ron Cooper, President and Chief Executive Officer of Albireo. "These results not only give us confidence in the potential for Bylvay in patients with PFIC, but also in our global pivotal studies in biliary atresia and Alagille syndrome."

Long-Term Safety and Tolerability

PEDFIC 1 was the first and largest, global, pivotal Phase 3 study conducted in PFIC, which evaluated the efficacy and tolerability of Bylvay in reducing pruritus and serum bile acids in a randomized, double-blind, placebo-controlled trial, and PEDFIC 2 is a long-term, open-label Phase 3 extension study. Bylvay improved pruritus, cholestasis, and growth with durable effect.

The data being presented confirms the safety and tolerability of Bylvay in children with PFIC. The observed safety and tolerability profile of Bylvay was consistent across studies, treatment groups, and doses. The analyses discussed in this oral presentation include data for of the safety and tolerability of Bylvay in children with PFIC treated in both PEDFIC 1 and PEDFIC 2 treated for up to 48 weeks. No drug-related serious adverse events were reported in either PEDFIC 1 or PEDFIC 2. One patient in PEDFIC 1 and 3 patients in PEDFIC 2 treated with Bylvay withdrew due to an adverse event. There were low numbers of gastrointestinal adverse events; specifically, treatment-related diarrhea/frequent bowel movements was reported in 10% of Bylvay treated patients in PEDFIC 1 and 5% of placebo-treated patients.

Long-Term Benefits of Bylvay

The oral presentation shows data for secondary and exploratory efficacy outcomes from the PEDFIC 1 and PEDFIC 2 studies, including growth, hepatic chemistries, and sleep parameters. The PEDFIC 2 study observed two cohorts:

Cohort 1 consists of PFIC1 and PFIC2 patients from PEDFIC 1 who rolled into PEDFIC 2. This includes patients treated with Bylvay, as well as patients treated with placebo.

Cohort 2 consists of newly enrolled patients who did not participate in the PEDFIC 1 trial, including patients with PFIC1, PFIC2, PFIC3 and MYO5B deficiency.

At the PEDFIC 2 interim data cut, median duration of exposure to Bylvay was 43 weeks in patients treated with Bylvay, 36 weeks for cohort 1 patients previously treated with placebo in PEDFIC 1, and 19 weeks in cohort 2. Long-term treatment with Bylvay was associated with clinically meaningful, positive effects on cholestasis, growth, and sleep parameters in patients with PFIC. The totality of the data support the potential of Bylvay to provide benefits to patients with PFIC. Key findings include:

• Significant improvement in height and weight: Mean height Z scores in the patient group treated with Bylvay increased significantly from -1.6 to -0.5 (P=0.02) with 48 weeks of treatment; similarly, those in the treatment naive group experienced increases in height Z score with 24 weeks of Bylvay. Changes in weight mirrored those observed with height (e.g., weight Z scores in patients treated with Bylvay normalized over 48 weeks [P=0.02; P=0.03]).

• Significant decreases in total bilirubin and serum ALT: In addition to the previously reported decreases in pruritus and serum bile acids in PEDFIC 1 and PEDFIC 2, Bylvay also decreased total bilirubin levels by 20 - 25 µmol/L, further indicating an improvement of cholestasis.

• Reductions in the percentage of days needing help to fall asleep, needing soothing, and sleeping with caregiver: From weeks 24-48 with Bylvay (both groups), there were reductions in the percentage of days needing help to fall asleep (P<0.0001 vs P=0.005, respectively), needing soothing (P<0.0001 vs P=0.12), and sleeping with caregiver (P=0.001 vs P=0.15).

The long-term data from the PEDFIC 2 study collectively reaffirm Bylvay's potential to be the first drug treatment approved for patients living with PFIC, a devastating disease which is currently treated with surgical options including liver transplantation.

The abstracts will also be published as an abstract book in the Journal of Pediatric Gastroenterology and Nutrition (JPGN).

Validation of the PRUCISION Caregiver-Reported (ObsRO)Pruritus Measure

The PRUCISION observer-reported (ObsRO) pruritus measurement tool, which was developed to adequately measure pruritus in pediatric patients, was used in the Phase 3 PEDFIC 1 and PEDFIC 2 studies. The data shows that the PRUCISION ObsRO pruritus measure is reliable, valid, and sensitive to change, and as such, is appropriate for evaluating the effect of treatment on pruritus in PFIC and potentially in other pediatric CLDs. A clinically meaningful ObsRO score change threshold of −1.00 was established. The PRUCISION ObsRO pruritus measurement tool is also being used to assess the primary endpoint in the ongoing phase 3 ASSERT trial for children with Alagille syndrome.