dm+d

Unassigned

New Medicines

BylvayProgressive familial intrahepatic cholestasis (PFIC) in children

Information

Bylvay
New molecular entity
Albireo
Albireo

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Launched
Yes
Yes
Sep 21Approved in UK [14].
Jul 21Approved in US where the company are ready for immediate launch [12,13]
Jul 21Approved in EU [11].
May 21Recommended for EU approval by CHMP under exceptional circumstances – the full indication is ‘treatment of progressive familial intrahepatic cholestasis (PFIC) in patients aged 6 months or older’. Bylvay will be available as 200 µg, 400 µg, 600 µg and 1200 µg hard capsules. Under exceptional circumstances means an authorisation may be granted subject to specific obligations, to be reviewed annually [10].
Dec 20Albireo Pharma announces submission of a NDA to US FDA and a MAA to the EMA seeking approval of odevixibat for the treatment of patients with progressive familial intrahepatic cholestasis (PFIC) [9].
Dec 20EMA’s Paediatric Committee has agreed to Albireo’s odevixibat Pediatric Investigation Plans for PFIC and biliary atresia; the company anticipates potential regulatory approvals, issuance of a rare pediatric disease priority review voucher and launch in the second half of 2021 [9].
Nov 20Company are working to prepare to file a New Drug Application with the US FDA and the EMA in the early part of 2021.[9]
Oct 18Odevixibat receives Fast Track designation in US for PFIC [5]
Mar 17According to Albireo pipeline, PII studies have started [2].
Mar 17Has orphan drug status in the US & EU [2].
Nov 16Granted PRIME (PRIority MEdicines) status in the EU for treatment of PFIC. Albireo plans to initiate a pivotal clinical trial in PFIC in the US and Europe, and anticipates meeting with the US FDA regarding the planned trial in Q1 17 [2].

Category

An inhibitor of the ileal bile acid transporter (IBAT; also called the apical sodium-dependent bile acid transporter).
Estimated prevalence of PFIC varies between 1 in 50,000 and 1 in 100,000 [1].
Progressive familial intrahepatic cholestasis (PFIC) in children
Oral

Further information

Yes

Trial or other data

Nov 20Positive topline data announced from a PIII trial of odevixibat in PFIC. Odevixibat met its primary endpoints in the PEDFIC 1 study and statistically significant reductions in serum bile acids (sBAs) and improvements in pruritus in pediatric PFIC patients were seen. Additionally, long-term data from PEDFIC 2 (an open-label PIII extension study) demonstrate continued and durable reductions in sBAs, improvements in pruritus assessments and encouraging markers of liver and growth function after up to 48 weeks. Across both studies, odevixibat was generally well tolerated, and treatment-emergent adverse events were mostly mild or moderate.[9]
Sep 20Primary endpoint is met in PIII PEDFIC 1 study. Odevixibat reduced serum bile acid responses (p=0.003) and improved pruritus assessments (p=0.004) vs placebo [8].
Jul 20PIII trial NCT04336722 (BOLD) starts, this is a randomized, placebo-controlled trial to evaluate efficacy and safety of odevixibat in children who have biliary atresia and have undergone a Kasai procedure before age three months. Dose will escalate to 120 μg/kg orally once daily for 24 months. Primary efficacy endpoint is improvement in the proportion of patients who are alive and have not undergone a liver transplant after two years of treatment [7].
Aug 19PIII PEDFIC-1 study is recruiting and expects to complete collection of primary outcome data in Dec 19 [6].
Sep 18Phase III PEDFIC 2 trial (NCT03659916) initiated in the EU and US to evaluate long term safety and efficacy of odevixibat in children with PFIC types 1 and 2. [4]
May 18First patient enrolled in the Pivotal phase III PEDFIC-1 trial (NCT03566238) of odevixibat in patients with PFIC. The randomised, double-blind, placebo-controlled trial will enrol approximately 60 patients in the EU and US [3]
Mar 17Albireo announces results from a PI trial that evaluated the safety, pharmacokinetics and pharmacodynamics of A4250 in healthy volunteers [2].

Evidence based evaluations

BylvayAlagille syndrome - first-line

Information

Bylvay
Licence extension / variation
Albireo
Albireo

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

An inhibitor of the ileal bile acid transporter (IBAT; also called the apical sodium-dependent bile acid transporter). Taken once daily.
A rare syndrome variably characterized by chronic cholestasis due to paucity of intrahepatic bile ducts, peripheral pulmonary artery stenosis, vertebrae segmentation anomalies, characteristic facies, posterior embryotoxon/anterior segment abnormalities, pigmentary retinopathy and dysplastic kidneys. Prevalence is ~1 per 70,000. Treatment includes high-carbohydrates, high-medium chain triglyceride diets and vitamins, and drugs for pruritus. Liver transplant may be needed in refractory cases [1].
Alagille syndrome - first-line
Oral

BylvayBiliary atresia post kasai procedure

Information

Bylvay
Licence extension / variation
Albireo
Albireo

Development and Regulatory status

Phase II Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

An inhibitor of the ileal bile acid transporter (IBAT; also called the apical sodium-dependent bile acid transporter). Taken once daily.
There are approximately fifty cases in the UK each year (1 in 15,000 births), but wide variation in incidence throughout the world (e.g. incidence is 1 in 5,000 in Taiwan).Approximately 20% have co-existing congenital anomalies, most commonly involving the heart, abdomen and genitourinary tract. There may be associated situs inversus or polysplenia/asplenia with or without other congenital anomalies [1].
Biliary atresia post kasai procedure
Oral