After Celgene’s blow-up last week with the Crohn’s disease candidate mongersen, the company is going back to what it knows best: Revlimid. And a disastrous third quarter has made its cash cow even more important.
While the group has been trying to reduce reliance on its best seller via deals, the multiple myeloma juggernaut might have more to give, with several trials in new indications set to read out in the near future (see table below). Success could boost Celgene’s sales by $1.5-2bn, a much-needed injection after the group just cut its long-term sales target.
The company had previously hoped to reach $21bn in revenues by 2020, but now says that it will only hit $19-20bn that year. The downgrade came as third-quarter sales disappointed, with the psoriasis therapy Otezla the main culprit, while Revlimid revenues also fell short of expectations. Celgene’s stock opened down 20% today.
Evercore ISI analyst Umer Raffat speculated that the third-quarter results might increase urgency for deals, but these have not always paid off for Celgene – a prime example is mongersen. The company gained the Crohn's disease candidate through its $710m acquisition of Nogra Pharma, but it failed in a late-stage trial last week (Celgene gutted as mongersen heads for the scrapheap, October 20, 2017).
This does not seem to have put Celgene off further deal-making. On the third-quarter call its chief executive, Mark Alles, said: “We will be very aggressive with our capital allocation and will continue to look for the right external opportunities.”
Executives were also optimistic about high-risk/high-reward bets, including the anti-BCMA CAR-T therapy bb2121, partnered with Bluebird Bio, and JCAR017, which Celgene is developing with Juno, noting that these are not expected to contribute much to the group’s top line until after 2020.
But in the meantime there is more pressure on Revlimid to expand into new indications, and its chance of success should soon become apparent. In late 2017 or early 2018 two trials are due to read out, Relevance and Augment; both test Revlimid plus Roche's Rituxan in follicular lymphoma, the former in first-line disease and the latter in relapsed/refractory patients.
|Study||Setting||Primary endpoint(s)||Trial ID||Data|
|Relevance||Revlimid + Rituxan in 1L follicular lymphoma||CRR, PFS, safety||NCT01476787||Q4 2017/ Q1 2018|
|Augment||Revlimid + Rituxan in relapsed/refractory follicular lymphoma||PFS||NCT01938001||Q4 2017/ Q1 2018|
|Robust||Revlimid + R-CHOP in 1L ABC DLBCL||PFS||NCT02285062||2018|
|Magnify||Maintenance therapy in relapsed/refractory follicular lymphoma||PFS||NCT01996865||2020|
|Source: Leerink note October 23, 2017.|
The idea is that the combination could help patients avoid chemotherapy; the current standard of care for follicular lymphoma is Rituxan plus a cytotoxic therapy.
Relevance will be classed as a success if Revlimid plus Rituxan outperforms the control arm, Rituxan plus chemo, which has historically shown median progression-free survival of 30-35 months, Leerink analysts noted.
However, the newer chemotherapy bendamustine, in combo with Rituxan, has shown PFS of 69 months – nearly six years – as well as better tolerability than older agents. Another challenge will likely come from Roche’s Gazyva, which is already approved in relapsed/refractory follicular lymphoma and expects an FDA decision in first-line disease by December 22.
Revlimid plus Rituxan will need to show PFS of close to five years to compete with these newer regimens, the Leerink analysts believe, which could be a big task.
Celgene’s drug might have a better chance in the relapsed/refractory setting, where the combination has been pitted against Rituxan plus placebo, and where it could be used in patients unable or unwilling to have chemotherapy.
Meanwhile, the Robust trial in first-line activated B-cell diffuse large B-cell lymphoma (ABC DLBCL) could provide a new option to this subgroup of patients, who are currently inadequately treated with R-CHOP chemotherapy, according to Leerink.
The Magnify maintenance study in follicular lymphoma could be a longer shot – it is investigating an induction therapy regimen comprising Revlimid plus Rituxan, followed by either Revlimid or Rituxan maintenance therapy.
Of course, Celgene’s attempts to expand Revlimid’s uses have not always met with success, with the Remarc failure scuppering plans in diffuse large B-cell lymphoma patients responding to chemotherapy (Revlimid blow highlights big cap exposure, July 26, 2016).
And the good times will not last forever: Revlimid is expected to face generic competition by 2022. However, in the meantime, Celgene needs to wring as much growth out of the product as it can while it waits for its longer-term bets to pay out.