Ash – Gallium might not be enough for Gazyva-Rituxan switch

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Replacing Rituxan with Gazyva in the treatment of first-line follicular lymphoma might not be as straightforward as the positive topline of the Gallium trial would suggest. Specialists will need to balance a delay in disease progression against an increase in side effects and unclear effect on overall survival.

As Roche prepares to detail full data from the trial at the Ash meeting next month, the Swiss group has to be aware of the limited window to establish Gazyva as its next-generation blood cancer drug. Celltrion’s Rituxan biosimilar could receive European approval soon, and its US submission might not be far off.

Early stop, but …

Gallium’s early stop after Gazyva showed clear superiority in progression-free survival gave hope of a clear-cut succession plan for Rituxan’s eventual fall (Asco preview – Proven approaches have their day, June 1, 2016). And the difference is highly significant – a 34% reduction in the risk of progression after an average of nearly three years of observation in this 1,202-patient post-chemotherapy maintenance trial.

Median progression-free survival (PFS) had not been reached in either arm – in previous follicular lymphoma trials, Rituxan’s median PFS has reached more than two years. Investigators, however, estimated that based on their risk calculation PFS in the Gazyva arm should be 1.5 times that of Rituxan – or nine years if Rituxan’s PFS is assumed to be six years.

The trial was a miss on overall survival, although with small numbers having died – 35 in the Gazyva arm and 46 taking Rituxan – the data are immature. Longer follow-up could yet yield a benefit.

With the new agent having not yet shown that it can extend patients’ lives, specialists will consider its safety profile carefully. A higher rate of severe adverse events, particularly infections, infusion-related reactions and secondary tumours, was detected, and this was highlighted by Dr Stephanie Lee, the Ash secretary, on a media call yesterday.

While toxicity is an issue with nearly all cancer drugs, in the case of maintenance therapy like Gazyva, taken up to two years, it is a greater concern than with something intended to be taken as an immediate, short-term treatment. And as payers consider the cost effectiveness of new agents, issues like treatment-related hospitalisation cost and toxicity-related quality of life declines can negatively affect the calculations.

The value dimension

When it comes to the cost-effectiveness question, Gazyva for now has the upper hand – US per-patient costs for the new drug were $43,792 in 2015 compared with $58,380 for Rituxan, according to EvaluatePharma. The older drug has undergone a series of price increases since 2010, when it was priced at $43,842; the expectation of biosimilar competition is the likely explanation.

That competition could emerge soon. Celltrion’s CT-P10, or Truxima, went to the European Medicines Agency in October 2015, and Teva has signed on as commercial partner in the US, where it is in a phase III trial due to read out in 2018.

The price of a biosimilar Rituxan will no doubt have an effect on how payers view Gazyva’s value. An overall survival benefit would help support a shift towards the new drug, but it is looking increasingly like Gazyva will not be a full replacement for Rituxan. The sellside’s consensus forecasts that sales of the new drug will grow by $2.5bn while the latter will shrink by $4.5bn.

Study Design Trial ID Ash abstract
Gallium Gazyva vs Rituxan, 1,200 follicular lymphoma pts post-chemo, measuring PFS NCT01332968 6

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @ByJonGardner on Twitter. For live updates from the Ash meeting in San Diego, on December 2-6, follow @ByJonGardner or @JacobPlieth on Twitter.

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