AbbVie, Genmab's lymphoma drug Epkinly snags FDA approval in heated blood cancer race

Big Pharma’s competition in the anti-CD20 bispecific space is taking shape, with the FDA on Friday approving what analysts view as a best-in-class blood cancer drug.

AbbVie and Genmab's epcoritamab has won accelerated approval to treat diffuse large B-cell lymphoma (DLBCL) after at least two lines of systemic therapy. The drug now bears the commercial moniker Epkinly.

A CD20xCD3 T-cell engager, Epkinly belongs to a class of drugs that also includes Roche’s first-to-market Lunsumio and its close-to-market glofitamab, plus candidates from Regeneron and a partnership between Johnson & Johnson and Xencor.

So far, Epkinly’s efficacy and safety data suggest it could be the best-in-class offering among CD20xCD3 bispecifics, William Blair analysts said in a December note. An SVB Securities team in February pegged Epkinly’s peak sales in the U.S. across all potential indications at nearly $3 billion before an expected patent cliff in 2036. The team figured the drug could collect similar sales outside the U.S.

Epkinly’s closest direct rival in DLBCL is glofitamab, which is due up for an FDA decision by July 1. The European Medicines Agency’s drug reviewers in April recommended an approval for glofitamab under the brand name Columvi.

In a phase 1/2 trial, Epkinly showed it could shrink tumors in 61% of patients who had tried a median of three prior lines of therapy, including 38% who saw no signs of cancer after treatment with the drug.

By comparison, in its own phase 1/2 trial, glofitamab triggered a response in 51.6% of patients who had undergone a median of three prior lines of treatment, with 39.4% experiencing a complete response rate. Both trials enrolled about a third of patients who had previously received CAR-T therapy.

Epkinly also appeared to have a better safety profile between the two meds. CD20xCD3 bispecifics work by directing T cells to target malignant B cells expressing CD20. In doing so, they may cause a well-known immune overreaction called cytokine release syndrome (CRS).

In their separate trials, Epkinly and glofitamab recorded CRS rates of 51% and 63%, respectively. Just 2.5% of patients who received Epkinly experienced serious CRS cases at grade 3 and above, compared with 3.9% for glofitamab.

Epkinly’s seemingly favorable efficacy-safety profile was somewhat surprising, because more severe CRS is expected from more potent drugs. That’s why Roche is directing glofitamab at aggressive lymphomas while using Lunsumio—a weaker but more tolerable agent—against indolent lymphoma types.

On the flip side, glofitamab did show longer duration of response. Roche has been touting its dosage approach of providing glofitamab for a fixed period of time, whereas rival meds are given until disease progression.

Another advantage for Epkinly could lie in its subcutaneous formulation. Compared with glofitamab’s intravenous infusion, an under-the-skin administration route makes Epkinly more convenient, which will be even more important in future combinations, Memorial Sloan Kettering Cancer Center lymphoma expert Lorenzo Falchi, M.D., said during a Genmab investor event in December.

Meanwhile, both Roche and the AbbVie-Genmab duo are exploring combos to move their CD20xCD3 agents into newly diagnosed DLBCL, a key battlefield for the drug class. There, AbbVie and Genmab are a bit ahead, having recently launched the phase 3 EPCORE DLBCL-2 trial using Epkinly on top of the standard R-CHOP regimen in newly diagnosed patients. Roche has said it plans to start a phase 3 for glofitamab in the same setting this year.

Front-line DLBCL is a tough nut to crack. Roche’s Polivy just won a hard-fought FDA approval in that setting after the agency questioned whether its regimen’s tumor progression advantage over R-CHOP—without a life extension benefit—is clinically meaningful. It’s also hard to tell from early clinical data whether Epkinly or glofitamab will eventually succeed, because the R-CHOP regimen is very powerful.

Outside of DLBCL, AbbVie and Genmab are also looking to challenge Lunsumio’s position in follicular lymphoma (FL). The pair has encouraging early-stage data for its approach of combining Epkinly with the R2 regimen—Revlimid and Rituxan—in first-line FL. But given that FL is an indolent disease, the development timeline could be long in the setting, the William Blair team noted.

Also in the CD20xCD3 field, Regeneron has odronextamab, which recently reported a 49% objective response rate in large B-cell lymphoma patients who had not tried a CAR-T therapy. And a high CRS rate, highlighted by a previous FDA partial clinical hold, doesn’t look flattering. J&J and Xencor's plamotamab is currently viewed as the least competitive within the class.

AbbVie signed up to co-develop and co-commercialize Epkinly with Genmab through a broad deal the companies inked in June 2020. At the time, the Illinois pharma giant paid the Danish antibody specialist $750 million upfront and committed up to $3.15 billion in milestones for certain rights to three bispecific antibodies and to partner on drug discovery efforts.

Genmab’s research has produced several commercial products. These include J&J’s blockbuster CD38 multiple myeloma drug Darzalex and the company's newly approved BCMAxCD3 bispecific Tecvayli, plus Horizon Therapeutics’ thyroid eye disease drug Tepezza, which is the crown jewel in Amgen’s proposed $27.8 billion acquisition of Horizon.

Editor's note: A previous version of the study mistakenly named Blincyto, the first FDA-approved bispecific T-cell engager, as a drug made by AbbVie. It's marketed by Amgen.

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