NICE UK approves Odiviximab (Bylvay) in PFIC 1 & 2

NICE UK approves Odiviximab (Bylvay) in PFIC 1 & 2

PFIC is a rare and serious genetic condition that reduces or stops the flow of bile acids from the liver. It has 6 subtypes.?The prevalence of PFIC in England is unknown. However, worldwide estimates range between 1 per 50,000 to 1 per 100,000 live births. And there are no licensed medicines for PFIC. Current options include - off-label medicines (for example, ursodeoxycholic acid, rifampicin, cholestyramine).?

NICE UK recently (22 Feb 2022) recommended Odiviximab (Bylvay) for people aged 6 month or older with?Progressive familial intrahepatic cholestasis (PFIC1 & 2) based on the?PEDFIC1 and?PEDFIC2 trials.?The company’s cost-effectiveness estimates were above what NICE usually considers acceptable, however?when taken all key assumptions into account, the cost effectiveness of odevixibat is likely to be lower than the company’s estimate. ERG’s scenario using a start age of 3 years reduced the ICER.

Approved dosage: The starting dose is 40 micrograms/kg/day that may be escalated to 120 micrograms/kg/day if there has not been an adequate clinical response.??

The submission included a Semi-markov model based on the 6 states-?Response and Loss of response for serum bile acid (sBS), Response and Loss of response to PEBD, a Liver transplant (LTx), after a Liver transplant and Death.

Market authorization covered all subtypes; however, reimbursement covered only PFIC 1& 2. The study had 5 PFIC3 patients and 1 PFIC6 but the effect could not be assessed in?them.

Key model assumptions: -

• Bile acid response was considered correlated with Pruritus which is a complex assumption
• People having standard care with off-label medicines were assumed not to have a serum bile acid response??
• It was also assumed that people moved up to the higher dose of odevixibat if there was no response after 6 months of continuous treatment at 40 micrograms/kg/day??
• The company assumed that people entered the model at the age of 4.25 years (the average age in PEDFIC1 trial).?However, ERG concluded that the basic model structure was appropriate for decision making, but that people may start odevixibat younger than assumed in the company’s model.
• High-dose odevixibat usage were calculated using data from few people (ERG highlighted)
• It was also assumed that, in 5% of people, the response to PEBD would be lost in each cycle.?
• The company’s costs consideration for PEBD included repeated surgeries for 67% of people, with equal costs applied to each surgery. This was an overestimate according to ERG.
• It was assumed in the model that most people have a liver transplant did so because of uncontrolled pruritus.??

After the second ERG meeting - the following assumptions were considered most appropriate-

• Including PEBD in the standard care arm only using rates from the NAPPED data
• The model used a start age of 4.25 years (the average age in PEDFIC1), although actual age might be lower than this
• Same probability to be used for liver transplant for odevixibat and PEBD loss-of-response health states
• Using the utility value from the ulcerative colitis study
• Using mortality rates for the acute and long term after a liver transplant from the ERG’s analyses??
• Applying a hazard ratio of 4.79 in the first cycle only to the proportion of people with a second transplant
• Excluding carers productivity costs.
• Including costs of common adverse events from PEDFIC1

“Note- Using these assumptions, the cost-effectiveness results for odevixibat compared with standard care were considerably lower than the company’s and ERG’s base cases.”

Uncertainties highlighted by EGR-

• It had been presented with very limited data for people with PFIC types other than PFIC1 and PFIC2
• There was no data for odevixibat when used before or compared directly with PEBD?
• The long-term effectiveness of odevixibat on survival, time to a liver transplant and use of SBD was unclear?
• The proportion of people whose condition stopped responding to treatment and the response rates to high-dose odevixibat were uncertain?
• There was no evidence that used the dose escalation schedule in the marketing authorisation that would be used in NHS practice

“Note - The committee acknowledged that some of these uncertainties could be resolved with data collection. Also, the committee concluded that additional data for odevixibat that would reduce the clinical-effectiveness uncertainty was expected in the near future.”

The model did not capture the following parameters which could have affected the results further: -

• Health benefits due to delaying or stopping lifelong immunosuppression
• Effect on QoL of carers
• Young age at which PFIC can develop
• Innovative nature of odevixibat

Odevixibat is available as a pack of 30 capsules. The cost per pack of 200 microgram capsules is ￡2,620, per pack of 400 microgram capsules is ￡5,240, per pack of 600 microgram capsules is ￡7,860 and per pack of 1,200 microgram capsules is ￡15,720 (excluding VAT; company’s evidence submission).

Overall, the company has positioned odevixibat as a first-line treatment for PFIC

For more detail refer to the submission –

·???????https://www.nice.org.uk/guidance/gid-hst10043/documents/final-evaluation-determination-document

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