March is shaping up to be a big month for Bristol-Myers Squibb’s ipilimumab. There is strong betting that it will receive FDA approval for second-line use in metastatic melanoma and may also before the end of the month read out pivotal data in the wider first-line population.
A win on both counts would be an important win for the US pharma giant, one of the most exposed to major patent expiries for key drugs over the next three years with $8.2bn of sales at risk (Pfizer patent cliff dwarfs peers as loss of Lipitor looms, February 1, 2011). Positive data in first-line use could result in blockbuster forecasts for the drug now branded as Yervoy, already expected to be BMS’ fifth-largest sales growth driver over the next six years.
|% of market cap||7%|
|Event type||PDUFA date||Phase III results|
|Indication||Metastatic melanoma, second line||Metastatic melanoma, first line|
|Date||March 26, 2011||Q1 2011|
Ipilimumab was long considered a high-risk venture in the cancer space, but hopes have revived on the strength of overall survival data reported last year (Asco - Pivotal data points to revival for BMS' ipilimumab, June 7, 2010).
BMS acquired the treatment and an antibody technology platform as part of its $2.4bn purchase of Medarex.
If approved, ipilimumab is likely to be a much-welcomed treatment in melanoma, where tumours often go unnoticed and spread widely before diagnosis. In addition, melanoma cells are very aggressive and often resistant to chemotherapy and radiation therapy.
Other than experimental drugs in clinical trials, the main option is dacarzabine, which has severe side effects such as infections, anaemia and fatigue as a result of suppressed immunity and blood-cell production.
A number of novel treatments are queuing up to fill the unmet need, ranging from vaccines to gene therapy (Therapeutic focus - Melanoma awaiting breakthrough but data approaching, September 10, 2010). Demonstrating the interest in the field, Daiichi Sankyo this week purchased Plexxikon, which has a leading candidate in the field in PLX4032, for $805m upfront in a deal valued at $935m (Daiichi pays handsome price for Plexxikon, March 1, 2011).
But with a PDUFA action date of March 26, ipilimumab faces the first yes-or-no decision of the new crop of treatments.
Unusually for a new product, the FDA has dispensed with an advisory committee meeting, saying the scientific questions the expert panellists were to consider have been answered (Event - Comeback kid ipilimumab looking good for FDA panel, November 24, 2010). Meeting with investors in early January, BMS chief executive Lamberto Andreotti said labelling discussions were ongoing and he was encouraged by the panel’s cancellation.
Most analysts are betting on approval, with analysts from Jefferies reasoning that if there were any concerns the regulator would have sent a complete response letter by now.
Premium pricing is expected, coming in at $100,000 per treatment course according to Cowen analysts. EvaluatePharma’sconsensus forecasts for the drug sits at $879m for 2016, valuing the therapy at $3.2bn, making the Medarex acquisition seem like good value should approval be granted.
Should it also succeed in the first-line setting, ipilimumab could prove to have greater value. Read out on the 500-patient trial is event driven, and many believe data could come by the end of March; recruitment is complete.
The trial tests a combination of the antibody with dacarzabine against dacarzabine alone. Analysts from Cowen, Jefferies and Bernstein all anticipate a survival benefit.
Depending on how the trial is powered, a significant improvement in survival may be detected if the patients taking ipiliumumab plus dacarzabine live at least 13 months and the patients in the control arm live 10 months or less, according to Cowen analysts. Historically, dacarzabine median survival is 6 to 10 months.
Analysts note, however, that should ipilimumab receive approval in the second-line setting, a first-line endorsement may have a limited commercial effect because all patients will likely see ipilimumab through the course of their disease. Thus approval in second-line is the key catalyst for the drug.
With expectations built this high, ipilimumab can hardly afford a misstep. The signs seem good for approval in the second-line setting, and with a growing belief that the first-line trial will show a positive benefit, any hiccup would be a big disappointment.