GSK’s antibody-drug conjugate Blenrep looked like a breakthrough in multiple myeloma when it was approved in 2020, even as a fifth-line treatment for the difficult blood cancer. Just two years later, though, the drugmaker had to pull Blenrep from the market due to a failed confirmatory trial.
But GSK didn’t give up on its promising ADC, which targets the B-cell maturation agent (BCMA) commonly found in patients with multiple myeloma, and the company yesterday revealed overall survival data that could set Blenrep up for a blockbuster comeback. In combination with chemotherapy and a steroid, Blenrep reduced the risk of death by 42% compared to Johnson & Johnson’s standard-of-care, second-line treatment Darzalex. The results were revealed at the American Society of Hematology annual meeting.
Blenrep’s potential re-entry into the multiple myeloma space comes when the market has plenty on the horizon, with cell therapies and bispecific antibodies poised to make a bigger splash in years ahead.
Still, GSK is confident it has a game-changer on its hands.
“We’ve seen a lot of great progress being made in multiple myeloma over the past several years, which is really important for patients,” said Dr. Hesham Abdullah, global head of oncology R&D at GSK. “When you could potentially be improving five-year survival rates for patients, you’re doing something that is really impactful … and [these studies], along with this overall survival data, provide an important data point and body of evidence supporting the use of Blenrep-based combinations moving forward for patients with relapsing multiple myeloma.”
A changing landscape
When Blenrep won an accelerated approval in 2020, it was the first BCMA-targeting treatment to get the regulatory go-ahead. But pharma has been busy with multiple myeloma in the years since then.
Approvals for BCMA-targeting cell therapies like Abecma from Bristol Myers Squibb and Carvykti from Johnson & Johnson, as well as bispecific antibodies such as J&J’s Tecvayli and Pfizer’s Elrexfio, have entered the scene — while Blenrep has been sidelined.
For Abdullah and his team at GSK, it took resilience to go back to the drawing board and prepare the drug for its next stage, all while learning from the past.
“I reflect on this a lot, and this journey has been one of those unique experiences that drug developers don’t often go on,” Abdullah said. “We looked really closely at the data … and part of it was going back and saying, ‘How do we look at the mechanism of action of this drug?’”
That meant finding the silver linings, like a 41% response rate in patients who were already heavily pre-treated and a response duration of more than 25 months — a result that was “probably unheard of for an antibody-drug conjugate in a late-line patient population,” Abdullah said.
Those takeaways set the stage for two head-to-head late-stage studies: DREAMM-7 against the Darzalex combo, which led to the most recent survival data, and DREAMM-8 against a combo with the older drug Velcade, which earlier this year demonstrated a 48% reduction of disease progression or death.
“We were very confident in the outcome of the DREAMM-7 and -8 results,” Abdullah said. “We had great support and partnership of key external experts and colleagues from around the globe that told us to continue.”
Blenrep also has an advantage over other BCMA-targeting drugs, particularly in terms of hospitalization, the long turnaround times associated with CAR-T cell therapies and some infection-related side effects of bispecific antibodies, according to Dr. Maria-Victoria Mateos, lead investigator of the DREAMM-7 study.
When it comes to Blenrep, Mateos called the results a “potential paradigm shift.”
‘A hard road’
Before Blenrep reaches blockbuster potential, GSK will need to find the right dosing regimen for different multiple myeloma patients, said Citeline senior analyst David Dahan. Some physicians might be cautious about toxicity, he said, particularly with side effects that induce blurred vision and cause about 10% of patients to discontinue use.
“I reflect on this a lot, and this journey has been one of those unique experiences that drug developers don’t often go on.”
Hesham Abdullah
Global head of oncology R&D, GSK
“[GSK] is going to have to show some new clinical data showing a safer dosing regimen,” Dahan said, pointing out that reduced dosing could have the same efficacy — a “less is more” approach. “Is it going to reach blockbuster status? It may eventually, but it is going to be a hard road.”
Abdullah said GSK is exploring the dosing options.
“[We are] looking at lower doses, more extended schedules — our focus is continuing to better enhance the overall profile of Blenrep, especially as we start thinking about moving into front-line patients,” Abdullah said.
With an expected decision from the FDA next year, the company has forecast peak annual sales of $3.8 billion.
And although bispecifics are currently approved in much later lines of treatment, they could start moving up the line, driving more competition against Blenrep, Dahan said.
Still, Blenrep could become the flagbearer for other medications in GSK’s pipeline.
“As we’re rebuilding the pipeline and continuing to expand, we’re also looking at … other therapeutic modalities that we’ll be bringing into our repertoire, including in multiple myeloma,” Abdullah said, adding that this could include “a next generation of antibody-drug conjugates.”
