2 The technology

2 The technology

Description of the technology

Carfilzomib (Kyprolis, Amgen) is an irreversible proteasome inhibitor that binds to the N-terminal threonine site, causing degradation of the proteins in the cell. It is given intravenously.

Marketing authorisation

Kyprolis in combination with either lenalidomide and dexamethasone or dexamethasone alone is indicated for the treatment of adult patients with multiple myeloma who have had at least 1 prior therapy.

Adverse reactions

The most common adverse reactions (in more than 20% of patients) were: anaemia, fatigue, diarrhoea, thrombocytopenia, nausea, pyrexia, dyspnoea, respiratory tract infection, cough and peripheral oedema. For full details of adverse reactions and contraindications, see the summary of product characteristics.

Recommended dose and schedule for carfilzomib

(1 cycle=28 days)

In combination with lenalidomide and dexamethasone

  • Carfilzomib is given on 2 consecutive days, each week for 3 weeks (days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (days 17 to 28) for the first 12 cycles.

  • From cycle 13, the day 8 and 9 doses of carfilzomib are omitted.

  • Carfilzomib is administered at a starting dose of 20 mg/m2 (maximum dose 44 mg) in cycle 1 on days 1 and 2.

  • If tolerated, the dose should be increased to 27 mg/m2 (maximum dose 60 mg) from day 8 of cycle 1.

In combination with dexamethasone alone

  • Carfilzomib is given on 2 consecutive days, each week for 3 weeks (days 1, 2, 8, 9, 15, and 16) followed by a 12-day rest period (days 17 to 28).

  • Carfilzomib is administered at a starting dose of 20 mg/m2 (maximum dose 44 mg) in cycle 1 on days 1 and 2.

  • If tolerated, the dose should be increased to 56 mg/m2 (maximum dose 123 mg) from day 8 of cycle 1.

For further details, see the summary of product characteristics.

Price

The list price of carfilzomib is £1,056 for a 60-mg vial (excluding VAT; MIMS online, accessed October 2016).

In combination with lenalidomide and dexamethasone

  • From cycle 1 to 12: £5,127 (no wastage), £6,336 (wastage)

  • From cycle 13: £3,418 (no wastage), £4,220 (wastage)

In combination with dexamethasone alone

  • £10,644 (no wastage), £12,627 (wastage)

The company has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the list price of carfilzomib, with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence. The Department of Health considered that this patient access scheme would not constitute an excessive administrative burden on the NHS.

  • National Institute for Health and Care Excellence (NICE)