Asco 2016 – Darzalex tries to climb the myeloma ladder
Darzalex looks like it could climb from fourth to first-line use with the full release of data from the Castor combination study with Velcade. Johnson & Johnson and Genmab’s CD-38 antibody induced a reduction in disease progression in relapsed or refractory multiple myeloma patients that was “unprecedented”, in the words of the study’s lead investigator.
The study had been terminated early for positive efficacy, so good results were obviously expected. In fact their strength raises the possibility that Darzalex and Velcade will become the new standard of care in this setting. But cost is a rising concern in multiple myeloma, and this combination may face pressure from payers.
In combination with Velcade and dexamethasone, Darzalex reduced the risk of progression by 61% compared with the two older agents alone. Patients on Velcade and dexamethasone had median progression-free survival of 7.2 months, while in the Darzalex arm a median progression-free survival number had not been reached at 15 months of analysis.
The antibody is currently approved as a monotherapy for patients who have previously received three lines of therapy, including a proteasome inhibitor like Velcade and an immunomodulatory agent like Revlimid. Patients are treated until disease progression, with dosing once a week for the first eight weeks, becoming less frequent afterwards.
The Velcade-Darzalex combination used Velcade for eight treatment cycles and Darzalex until progression, as it is currently labelled in later line use.
The 61% reduction in the risk of progression exceeded the achievements of other treatments in this setting, said the lead study author, Antonio Palumbo, chief of the myeloma unit at the University of Torino. Dr Palumbo said the combination “might be considered to be a new standard of care” with the release of these data.
The cost factor
Multiple myeloma has represented one of the fastest-moving areas in oncology, with agents like Pomalyst, Empliciti, Farydak, Kyprolis and Ninlaro all having come onto the market in the last three years. Many of course, are used in combination, with a backbone of dexamethasone and Celgene’s Revlimid.
A recent draft report from the Institute for Clinical and Economic Research (ICER) analysed emerging new therapies and found that none of them could be considered cost-effective if the threshold is set at $50,000 per quality-adjusted life year gained.
The group determined that the budgetary impact of three of the newer agents – Amgen’s Kyprolis, AbbVie and Bristol-Myers Squibb’s Empliciti, and Takeda’s Ninlaro – in combination with Revlimid and dexamethasone, could be $951m a year.
Darzalex’s list price is steep. ICER puts it at $4.50 per milligram, with a 16mg/kg dosing regimen: at an average weight of 89 kg for American men, that equals $6,400 per cycle. Taken weekly over the first eight weeks, every other week through week 24, monthly after that, and ceasing only on progression, the cost implications of this combination are immense when considering that Velcade alone is already $54,000 per patient per year, according to EvaluatePharma’s sales, volume and pricing data.
Moreover, in the days leading up to Asco, Genmab announced that the Pollux first-line trial of Darzalex with Revlimid and dexamethasone had scored a win, with a 63% improvement in progression free survival. The cost of Revlimid and dexamethasone already is $240,000, according to ICER.
ICER did not prepare a cost-effectiveness analysis of Darzalex in its licensed indication because patients are so advanced and because there is no comparative treatment. However, this is likely to change when it moves into first line treatment.
The survival benefit will no doubt balance out some of the increased cost. However, ICER has noted that Kyprolis, Empliciti and Ninlaro will need to cut their unit prices by at least one-third, and by as much as 94%, to meet value-based price benchmarks, and for treat-to-progression drugs, “greater discounts are required”.
It is hard to see Darzalex escaping that fate.