The UK’s National Institute for Health and Care Excellence (NICE) has re-examined its draft guidance for pixantrone (Pixuvri) but come to the same conclusion as before.
The organization is still not recommending pixantrone monotherapy to treat multiply relapsed or refractory B-cell non-Hodgkin lymphoma (NHL).
Of course, this recommendation may change, as this is not NICE’s final guidance on pixantrone.
For this second consultation on the draft guidance, an independent appraisal committee re-examined the clinical and cost-effectiveness of pixantrone.
This time, the committee took into consideration a patient access scheme submitted by pixantrone’s manufacturer, Cell Therapeutics. The scheme was designed to make the drug more cost-effective for the National Health Service (NHS).
“Unfortunately, the committee concluded that this scheme . . . does not overcome the uncertainties in the evidence for the drug’s clinical effectiveness over and above current treatments for this disease,” said NICE Chief Executive Sir Andrew Dillon.
In fact, the committee found the scheme did not make pixantrone cost-effective according to the accepted definition—costing £20,000 to £30,000 per quality-adjusted life year (QALY) gained.
Evaluating trial data
When considering the clinical effectiveness of pixantrone, the appraisal committee analyzed data from the EXTEND PIX301 trial, which was submitted by the manufacturer.
The trial enrolled adults with aggressive, de novo, or transformed NHL that had relapsed after 2 or more chemotherapy regimens, including at least 1 standard anthracycline-containing regimen with a response that lasted at least 24 weeks. Seventy patients were randomized to pixantrone, and 70 were randomized to a physician’s choice of single-agent comparators.
The committee pointed out a number of uncertainties associated with the trial. One was that it did not include the planned number of patients (which was 320), so it may not have been sufficiently powered to detect differences between the treatment arms.
Another concern was that the trial’s primary endpoint was complete or unconfirmed complete response, rather than overall survival or progression-free survival. In fact, there was a lack of statistically significant difference in overall survival between treatment arms. And other differences between the treatment arms were not always statistically significant.
These factors led the committee to conclude that there is insufficient evidence to suggest pixantrone is more clinically effective than treatments currently used in clinical practice.
Suitability for the UK
The appraisal committee also heard evidence from clinical experts and patient representatives. This information revealed differences in previous treatment between the PIX301 trial population and UK clinical practice.
Therefore, the committee said it could not determine the clinical effectiveness of pixantrone for a UK population.
In addition, there is doubt regarding the clinical benefit of pixantrone in patients who previously received rituximab. And this applies to virtually all patients with relapsed or refractory aggressive B-cell lymphoma in England and Wales, the committee noted.
(The European Medicines Agency’s conditional approval of pixantrone stipulated that an additional trial must confirm the clinical benefit of the drug in patients who have previously received rituximab.)
Calculating costs
The committee estimated the patient access scheme for pixantrone would most likely result in an incremental cost-effectiveness ratio of £30,700 per QALY gained. This is above the range normally considered to be cost-effective—usually £20,000 to £30,000 per QALY gained.
This factor, along with the lack of clinical effectiveness, prompted the committee to conclude that pixantrone would not be a cost-effective use of NHS resources.
According to Cell Therapeutics, pixantrone costs £553.50 per 20 mL vial. The recommended dosage of pixantrone is 50 mg/m2 on days 1, 8, and 15 of each 28-day cycle, for up to 6 cycles.
The estimated cost of a course of treatment is £19,926. This is based on the median length of treatment in the PIX301 trial—4 cycles, using an average of 3 vials per dose.
About the guidance
Individuals can comment on the pixantrone draft guidance via the NICE website. It is open until November 4, 2013.
This is the third version of the draft guidance published and the second consultation launched. The draft guidance was initially published for consultation in April 2013, followed by a final draft guidance in June 2013. But this document was withdrawn during the appeal stage because the manufacturer submitted the patient access scheme.
Until the final guidance is issued to the NHS, organizations should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.
