Celgene Targets Blood Cancers with Major Buys

Celgene inked two multibillion dollar deals in January, buying Seattle, WA–based Juno Therapeutics, a developer of chimeric antigen receptor (CAR) T-cell therapies, and Impact Biomedicines of San Diego, CA, which is testing a JAK2 inhibitor.

One impetus for the acquisitions is the pending arrival of generic competition for Celgene's most profitable drug, lenalidomide (Revlimid). Usually prescribed for the treatment of multiple myeloma, lenalidomide generated global revenue of nearly $7 billion in 2016. To drive new growth, Celgene announced on January 7 that it will buy Impact for $1.1 billion up front and another $5.9 billion in potential milestone payments. Two weeks later, plans to take over Juno for approximately $9 billion were announced.

“They're staring down Revlimid's patent expiry in a couple of years,” says David Nierengarten, PhD, head of health-care equity research at Wedbush Securities in San Francisco, CA. The acquisition of Impact in particular “shows that they were really looking for potential near-term revenue opportunities that can fill that hole.”

Impact's JAK2 inhibitor fedratinib will likely be the first financial stopgap. Phase III trial data showed that 35% to 40% of patients with previously untreated myelofibrosis taking the drug experienced a reduction in spleen volume, compared with 1% of those taking a placebo (JAMA Oncol 2015;1:643–51). A phase II single-arm trial of patients with the rare bone marrow cancer who did not respond to the JAK1/2 inhibitor ruxolitinib (Jakafi; Incyte) had even better outcomes, with 55% displaying a splenic response (Lancet Haematol 2017;4:e317–24).

A regulatory filing for fedratinib is anticipated later this year. If approved, analysts believe the drug could generate sales of up to $1 to $2 billion annually. The real moneymaker, though, could be Juno's pipeline of CAR T and T-cell receptor therapies now in early-stage trials.

Gilead Sciences, of Foster City, CA, made a similar bet on CAR T-cell therapies last August when it spent nearly $12 billion for Kite Pharma in Santa Monica, CA. Then, on January 23, the company helped bankroll Tmunity Therapeutics, spun off from the University of Pennsylvania in Philadelphia, which counts CAR T-cell pioneer Carl June, MD, among its founders.

The Kite buyout started to pay off in October when the anti-CD19 CAR T-cell therapy axicabtagene ciloleucel (Yescarta) earned FDA approval for patients with refractory or relapsed large B-cell lymphoma.

None of Juno's candidates are as far along, but the company does have a variety of promising agents, at least eight of which are in clinical development for a range of hematologic and solid cancers. These include an anti-BCMA CAR T-cell therapy for multiple myeloma that supplements Celgene's only prior CAR T agent, bb2121, under development with bluebird bio.

However, the lead asset in Juno's collection is JCAR017 (lisocabtagene maraleucel), an anti-CD19 CAR T-cell therapy that the company pushed forward after halting the development of JCAR015 following five deaths in 2016. With that setback, Juno fell behind Kite/Gilead and Novartis, the other company with an approved CAR T-cell therapy. However, Nierengarten says that might not be detrimental.

Nierengarten cites the difficulties Kite/Gilead has faced in securing reimbursement for axicabtagene ciloleucel, and he suggests Celgene could benefit from having a rival address regulatory hurdles first—especially if, as many observers suspect based on phase I data, JCAR017 proves to be best-in-class.

If JCAR017 garners approval next year, as anticipated, Celgene “can come in likely after the reimbursement paradigm has been mostly established and, hopefully, launch a safer and more efficacious product,” Nierengarten says. –Elie Dolgin

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