[ASH 2024] J&J targets curing half of muliple myeloma patients with innovative treatment portfolio

SAN DIEGO, Calif. – By Lee Han-soo/Korea Biomedical Review correspondent -- Johnson & Johnson has set an audacious goal to cure half of all multiple myeloma patients, marking a transformative shift from disease management to potential cure.

In an interview with Korea Biomedical Review at the American Society of Hematology (ASH) annual meeting, Mark Wildgust, Vice President of Global Medical Affairs at Johnson & Johnson, outlined the company's ambitious vision and comprehensive strategy to advance multiple myeloma treatment through its expanding portfolio of therapies.

The company's 15-year evolution in myeloma treatment began with the development of bortezomib in partnership with Millennium, now Takeda.

"More than 15 years ago, we started the development of bortezomib with our partner Millennium, now Takeda,” Wildgust said. Since then, the company has been developing myeloma therapies but also building regimens.

To date, the company has treated more than a million patients with multiple myeloma with one of its myeloma therapies, he added.

Wildgust further explained that the life expectancy of a patient with myeloma has significantly transformed during that timeline.

J&J's flagship therapy Darzalex (ingredient: daratumumab) has demonstrated remarkable success across multiple clinical trials.

"We have had 14 different phase 3 studies with Darzalex,” he said. “In every study where we use Darzalex, we see a significant improvement in progression-free survival and we've treated more than 600,000 patients.”

Wildgust stressed that it presents five studies at ASH 2024, which have shown the drug’s potential in newly diagnosed multiple myeloma settings.

The company's Carvykti therapy has shown unprecedented results in late-line treatment settings.

"I think the data we saw with Cartitude-1 in that late-line setting—a median of 6 lines of therapy, 80 percent of patients had four or more lines of therapy—we saw something unprecedented," Wildgust said. "For those patients who had six prior lines of therapy, triple refractory, many of them penta-refractory, their life expectancy would probably be about 12 months.”

What the company saw was a significant improvement in progression-free survival.

“The median progression-free survival for just Carvykti in that six prior lines therapy setting was more than three years,” he said.

The bispecific antibodies Tecvayli (ingredient: teclistamab-cqyv) and Talvey (ingredient: talquetamab-tgvs) represent another breakthrough in J&J's portfolio.

"Teclistamab is showing rapid and deep responses, low number of adverse events, and the weight-based dosing has provided a highly tolerable regimen for patients," Wildgust said. "Importantly, we've seen that with that rapid and deep response, you see long durable outcomes for those patients as well—median progression-free survival of about a year.”

Also, regarding the patients who reached complete response, the company has yet to see the median duration of response, he added.

Recent clinical trials have yielded promising results in various treatment settings.

The Aquila study, published simultaneously in the New England Journal of Medicine, demonstrated significant progress in treating smoldering myeloma.

"We know that patients with high-risk smoldering myeloma who are asymptomatic—these patients don't have those symptoms yet of myeloma,” he said. “They don't have renal failure, they don't have an osteolytic lesion, they don't have a pathological fracture, they don't have anemia or thrombocytopenia.”

These patients are asymptomatic, but these high-risk patients will turn into symptomatic patients within a couple of years, he added.

The company's commitment to innovation extends to exploring alternatives to traditional stem cell transplantation.

"If you look at the Cepheus data, which is our Darzalex in combination with bortezomib, lenalidomide, and dexamethasone (VRd) in transplant-ineligible patients, actually the outcomes for those patients are as good as VRD, the prior standard of care with transplant," Wildgust said. "When you look at some of the data that's coming out in terms of Carvykti—98 percent response rate in 6 lines of therapy, MRD rates that we have never seen before.”

In the Cartitude-4 study, nine out of 10 patients reached MRD negativity in the relapsed setting, and those data are better than chemo, better than induction transplant and consolidation, and those are in late lines of therapy, he added.

Addressing the healthcare burden in an aging population

Addressing the challenges of an aging population and healthcare system burden, J&J emphasizes the importance of effective first-line treatment.

"We're seeing around the world, particularly in developed countries, that people are living longer,” he said. “Myeloma's median age of diagnosis is somewhere in their mid-60s and I think that it does add more burden to the healthcare system.”

But a patient who has one line of therapy, two lines of therapy, 4, 5, 6 lines of therapy in themselves is burdensome to the healthcare system, he added.

To address this challenge, Wildgust emphasized the importance of using optimal treatments early.

"Using the best, most effective regimen first, having high levels of deep responses—it gives us the potential to give fixed duration treatments up front and be able to stop and have patients off therapy for long periods," he explained. "Particularly when you think about age expectations for patients around the world, 65-year-old people probably have a 20-plus year life expectancy.”

So there is a need to think about using the best agents first rather than using a suboptimal one, he added.

The Perseus study demonstrates this approach in action.

"The Perseus study is a great example of that—newly diagnosed transplant-eligible patients,” he said. “Those patients got Dara-VRD, transplant, and then they got Dara-Revlimid in maintenance.”

For those patients who were able to maintain sustained minimal residual disease those patients could then stop therapy and, two-thirds of patients in that trial were able to stop therapy, he added.

This strategy not only benefits patients but also addresses healthcare system constraints.

"We know that if you use suboptimal therapy first, first of all, a third to half of those patients may not make it to the second line,” he said. “But then we also know that your response to second-line therapy is never as good as using your best first.”

Evolution of precision medicine

The company's approach to precision medicine continues to evolve.

"When you think about precision medicine, you think about a target and how you can use that target," Wildgust said. "I don't think we're in a place where we could say, 20 percent of patients have this particular target so we should go after that.”

The vice president stressed that he believes that when thinking about biomarkers like BCMA, he knows that it's pretty broadly expressed on myeloma cells, so he can confidently say treat all patients with a BCMA-targeting agent or GPRC5D.

Looking to the future, J&J maintains ambitious goals.

"At Johnson & Johnson, our vision is to have one in two patients using one of our J&J medicines,” he said. “We have this audacious idea of trying to cure one in two patients as well.”

The company has a portfolio of immunotherapies that it believes are going to transform outcomes for myeloma, he added.

Wildgust expressed the company’s pride over its legacy in multiple myeloma.

“That legacy is one of innovation and transforming outcomes for patients,” he said. “We’re changing the conversation from managing disease progression to treating to cure."