GSK’s Benlysta Discount Isn’t Big Enough To Avoid NICE Rejection

NICE says GSK did not adequately compare its lupus drug belimumab to Roche’s Mab Thera (rituximab). While the firm and partner Human Genome Sciences did offer data that appeared to show an advantage, the problem is that the positive results were more prevalent in a patient population that did not broadly reflect the make-up of the U.K., NICE said.

The uptake of GlaxoSmithKline Inc./Human Genome Sciences Inc.’s systemic lupus erythematosus drug Benlysta (belimumab) in the U.K.’s National Health Service has suffered another significant blow, following a decision by the National Institute of Health and Clinical Excellence to reject the drug, principally on cost grounds.

NICE’s thumbs down for Benlysta in its Final Appraisal Determination highlights the pharmaceutical industry’s resentment of the institute’s evaluation practices and reinforces its contention that, at least in England and Wales, being both better than standard care and truly innovative is simply not enough.

Benlysta’s demise at NICE is not exactly a surprise – the institute initially rebuffed the drug in October 2011 – but GSK had expected to make a better showing, given that it had agreed a significant patient-access scheme, in the form of a hefty, yet undisclosed, discount with the Department of Health (Also see "GSK Gears Up To Fight NICE On Benlysta Setback" - Pink Sheet, 3 Oct, 2011.).

That Old Devil Called Cost-Effectiveness

But, once again for NICE, Benlysta’s cost-effectiveness was the sticking point. Even with the addition of the agreed-upon patient-access scheme, the drug generated an incremental cost-effectiveness ratio of £61,200 ($100,000) per quality-adjusted life-year gained. This is more than double of NICE’s upper-limit cost-effectiveness threshold of £30,000.

To try and get a drug through NICE despite being so far beyond the limit is a bit like banging your head against a brick wall, but miracles do happen – albeit not this time. “In certain cases, such as those where there are end-of-life considerations, once all of the relevant evidence has been considered, it might be possible for a positive recommendation to be made where an ICER remains above normally accepted threshold range even with the PAS [patient-access scheme] discount included,” a NICE spokesman said.

But GSK is disappointed with the NICE rejection of its patient-access scheme and says that it can go no further down this road. A spokesperson for the company pointed out that the list price of Benlysta is around the £9,000 mark and the company had gone below this for the patient-access scheme. She added that the cost for another therapy in this area, Roche’s Mab Thera (rituximab), was £7,000, and Benlysta represents an improvement.

“The NICE system does not have in it the nuances to be able to really reflect the benefit of an innovation – it treats everything the same,” the spokesperson charged.

No Rituximab Comparison, No Deal

But NICE essentially believes that the drug’s innovative benefit was not adequately shown, and central to that conclusion is its feeling that the sponsor lacked strong comparison data to Mab Thera. In the U.K., between 10%-15% of patients with systemic lupus erythematosus have high disease activity despite standard therapy – treatment with non-steroidal anti-inflammatory drugs, corticosteroids and/or immunosuppressants – and a proportion of these are treated with rituximab, frequently through individual funding requests. This is a locally managed process in which a clinician might request a specific treatment for a patient and it is up to the local primary care trust to decide whether to fund the request.

NICE clearly was unimpressed by what it felt was a serious omission of data. “Rituximab was included in the scope as a comparator for this appraisal as this reflects clinical practice, so it would be expected that any relevant evidence would be addressed in the submissions we received,” the NICE spokesperson said.

And the institute also suggested that GSK’s estimate of a six-year maximum treatment duration with Benlysta was somewhat arbitrary. Moreover, NICE was unconvinced that treatment effect was maintained over time, pointing out that if this were not the case, it could have a negative impact on drug’s cost-effectiveness.

GSK argues that its limit was based on robust assessment and was the result of a data-driven process, based on six-years of information compiled. “What we have said is that clinicians should use Benlysta for a maximum period of six years in order to enable them to make a judgment on the data that is then in existence,” the spokesperson said.

NICE’s rejection, though, is frustrating for the firm given that the institute accepted that, compared with standard care, there actually was some evidence of Benlysta’s clinical effectiveness. The problem is that the positive results appeared to be more prevalent in a study in which the patient population did not broadly reflect the make-up of the U.K., NICE said.

But the GSK spokesperson pointed out that within the patient subgroup for which it submitted data to NICE, there was an almost 20% difference in the response rate versus standard of care, representing a significant benefit. “This is proven treatment, with proven efficacy, particularly in that patient population,” she added.

NICE’s concerns about the duration of treatment effect seems to be shared to some degree by the European Medicines Agency, which requested that GSK address uncertainties about the effect of stopping treatment with belimumab (treatment holidays) as well as the risk of rebound phenomena.

GSK said it is doing just that, currently undertaking a long-term safety study, involving 5,000 patients over 10 years; phase II and III open label-extension studies; a study to investigate the effects of stopping treatment; a study with the British Society of Rheumatology registry, to generate real-life data; and an efficacy and safety of Benlysta in patients with lupus nephritis.

Quo Vadis Benlysta?

GSK says it is now debating as to whether it should submit an appeal, given the narrow technical criteria that NICE lays down that must be satisfied in order for this to be feasible: Essentially, the firm would need to present some new clinical data, and the window closes in two weeks. Meanwhile, the drug also is undergoing an added-benefit assessment in Germany, with a result due in a matter of days or weeks (Also see "Germany’s Pricing Revolution: Why The World Should Be Watching" - In Vivo, 24 Feb, 2012.).

As for any impact from the NICE decision on GSK’s bid for HGS, the spokesperson said that she could not possibly speculate on this (Also see "GSK And HGS Face Off Over Buyout" - Pink Sheet, 25 Apr, 2012.).