As Celgene touts the potential of Abraxane and apremilast to grow revenue and perhaps draw attention away from the flagging Revlimid, a third project, pomalidomide, has made quiet progress though development.
Newly released abstracts detailing phase III data to be presented at next month’s ASH meeting have confirmed pomalidomide’s potential in third-line multiple myeloma, and most analysts expect US approval early next year; consensus estimates have been creeping up, and some sell-side bulls even see near-blockbuster sales. Although it remains to be seen how the project fits into a changing landscape, it should give Celgene another shot at maintaining its growth trajectory.
|% of market cap||5%|
|Event type||PDUFA date|
|Indication||Third-line multiple myeloma|
|Date||February 10, 2013|
In pomalidomide Celgene has an agent that could bolster its Revlimid franchise and give Onyx Pharmaceuticals’ recently approved Kyprolis a run for its money.
Revlimid, which is approved for second-line multiple myeloma and used off-label in the US frontline setting, accounts for around 70% of Celgene’s group sales. But a quarter-on-quarter rise of just 2% in Q3 caused some alarm, with analysts highlighting the need for the company to find new growth drivers.
The slowdown was likely caused by Takeda’s launch of a subcutaneous form of Velcade, a rival multiple myeloma drug. Kyprolis, which could eat into Revlimid’s use in relapsed/refractory patients, is another worry.
Celgene filed pomalidomide with the FDA in April, and followed this up with an EU submission in May. An advisory panel meeting scheduled for this month was cancelled without the action date being altered – surely a positive sign.
The filings seek approval for use in patients who have failed at least two prior therapies – in practice Revlimid and Velcade – and were based on small phase II studies showing a 34% response rate. The open-label, phase I/II MM-002 trial resulted in median progression-free survival for pomalidomide plus dexamethasone of 4.7 months and overall survival of 16.9 months.
In the ASH abstract, from a much bigger, 426-patient, open-label phase III study (MM-003), pomalidomide showed median PFS of 3.9 months, and median OS had not yet been reached. Although the PFS benefit was smaller than in the earlier trial, UBS analysts said it would suffice, especially since safety was consistent with MM-002; they say they see “minimal risk” to US and EU approval.
While it is difficult to make comparisons in this third-line setting of very sick patients, it is worth noting that Kyprolis was approved based on a 23% overall response rate. RBC Capital Markets analysts say overall survival in Kyprolis studies was a similar 3.7 months, and expect regulators to consider MM-003 as part of the pomalidomide submission.
In any case, analysts’ growing bullishness is revealed by EvaluatePharma’s archived forecast data, which show an uptick in 2016 consensus sales estimates from just $43m in March 2011 to the current $294m. Revenue expectations in 2018 stand at $430m.
UBS is bolder still, forecasting $712m by 2015, although the analysts admit to being above consensus. They model eight cycles of therapy in the relapsed/refractory setting as opposed to three to five in the two studies.
One key to meeting such targets will be expanding use of pomalidomide beyond third-line multiple myeloma. Results from MM-005, a phase I trial in which pomalidomide is added on top of dexamethasone and Velcade, are also expected at ASH, and a phase III study in this setting could begin later this year.
And myelofibrosis, an indication in which Incyte’s JAK inhibitor Jakafi was approved last year, is another target; a 210-patient phase III trial is due to yield data in mid-2013, Celgene says.
Of course, it will not all be plain sailing, even if approval is a no-brainer. One problem is that pomalidomide is basically a follow-on version of Revlimid, and would surely cannibalise some Revlimid third-line sales – however cleverly Celgene will try to compartmentalise the market.
And in addition to the battle against Kyprolis, analysts have highlighted the potential of Bristol-Myers Squibb/Abbott Laboratories’ elotuzumab (BMS-901608), which in 2014 will yield data in the relapsed/refractory multiple myeloma setting, to shake up the market further.
Revlimid itself is far from down and out, and Celgene insists that there is much life in it yet. But should it stumble, at least the company has a plan B.
|Selected pomalidomide trials|
|MM-002||Phase I/II, 30 relapsed/refractory multiple myeloma patients||NCT00833833|
|MM-003||Phase III, 426 relapsed/refractory multiple myeloma patients||NCT01311687|
|MM-005||Phase I, multiple myeloma, addition to Velcade, 70 patients||NCT01497093|
|MM-007||Phase III, multiple myeloma, addition to Velcade||(not yet begun)|
|MF-002||Phase III myelofibrosis study, 210 patients||NCT01178281|
To contact the writer of this story email Jacob Plieth in London at firstname.lastname@example.org