Update 1: on November 24, 2010, the FDA announced the postponement of its advisory committee to review Yervoy (ipilimumab), originally scheduled for December 2, due to 'the need to complete the review of additional data submitted by the applicant' (Bristol-Myers Squibb).
Update 2: on December 30, 2010, the FDA announced that the advisory committee to review Yervoy (ipilimumab), which had been rescheduled for February 9, 2011, has been cancelled "because the issues for which the FDA was seeking the scientific input of the committee have been resolved." (http://www.fda.gov/AdvisoryCommittees/Calendar/ucm235827.htm) We assume the product's PDUFA of March 26, 2011 remains unchanged.
Bristol-Myers Squibb’s ipilimumab comes before an FDA advisory committee December 2, and a positive vote would be the icing on the cake for the novel immunotherapy’s surprising turnaround. Largely written off two years ago, the candidate managed to extend survival in incredibly challenging second-line metastatic melanoma patients, meaning backing by the regulator’s expert panel is anticipated (Asco - Pivotal data points to revival for BMS' ipilimumab, June 7, 2010).
On the horizon, however, awaits a second and potentially bigger prize: data in first-line melanoma patients and again hopes have been rising for the agent in this setting. As one of Bristol-Myers’ most important sales growth drivers the resurrection of ipilimumab (ipi) will be great news, and also represent a step forward for melanoma treatment, which has seen little improvement in options in the past 30 years (Therapeutic focus - Melanoma awaiting breakthrough but data approaching, September 10, 2010).
% of market cap
FDA advisory committee
Phase III results
Metastatic melanoma, second-line
Metastatic melanoma, first-line
December 2, 2010
Expectations are high for approval in the second-line setting and positive results in the first-line study. EvaluatePharma’s consensus estimates for 2016 sales have risen by 49% to $944m since Bristol-Myers Squibb announced results in the second-line setting at Asco.
While it does not match the potential of blood-thinner apixaban in the Bristol-Myers Squibb pipeline, ipi, an immunotherapy that is proposed to be marketed as Yervoy, is the group’s fifth-biggest growth driver. With a net present value of $3.36bn, the monoclonal antibody represents 8% of Bristol-Myers Squibb’s market capitalisation and alone justifies the $2.4bn purchase of ipilimumab originator Medarex, assuming the product meets expectations (Bristol-Myers gets its antibody deal at last, July 23, 2009).
As such, any stumble at this late stage is likely to disappoint investors who are looking for the company to replace blockbuster income from such products as the venerable Plavix, which loses patent protection in 2011.
The pivotal data unveiled at Asco compared ipi to an experimental vaccine called gp100 in a three-arm trial – the vaccine was a stand-in for IL-2, an immune boosting therapy with severe toxicity that limits its use, and was considered a relevant comparator as there is no therapy considered standard of care.
The ipi plus placebo and ipi plus gp100 arms had median overall survival of just more than 10 months, compared with 6.5 months for the gp100 vaccine plus placebo, and thus ipi demonstrated statistically significant improvement in survival.
FDA’s expert panel is likely to hone in on the choice of gp100 as a comparison drug, as well as ipi’s side effects, including severe diarrhoea, which require aggressive management. These questions may also have been the reasons behind the FDA’s request for additional data analysis, which extended the PDUFA date from December 25 to March 26, 2011.
In the first-line setting, data is expected in the first quarter of 2011, according to company executives. However the study is event-driven, and the read-out will be triggered by deaths in the 500-patient study, so these data could well arrive earlier or later than expected.
The study is fully recruited, and is measuring overall survival as a primary endpoint. Patients who have previously untreated stage III or IV unresectable melanoma are dosed with either dacarbazine and ipi, or dacarbazine and placebo. No doubt there is considerable hope for this setting, but it still seems likely that forecasts would increase should this study read out well in a much bigger population of patients.
FDA adcoms can be difficult to predict, but as the oncological drugs panel has scheduled to consider two in one day, there is a suggestion that both will be quick decisions (Event - Zictifa approval should be a little help for AstraZeneca, November 23, 2010). Given the lack of alternative treatments and the unmet medical need, the handicapping seems to be in favour of a positive adcom vote and FDA approval for ipi in the second-line setting.