Toward a functional cure: J&J's ambitions in multiple myeloma

This week’s Executive Interview, sponsored by Johnson & Johnson (NYSE: JNJ), is with the company’s senior director and EMEA therapeutic area lead in hematology, Edmond Chan, and Mario Klesse, regional commercial strategy leader in hematology.

In the little more than a decade since J&J intensified its research efforts in multiple myeloma, the company has managed to transform outcomes in this complex and hard-to-treat form of blood cancer.

J&J brought to market the first anti-CD38 antibody, targeting an antigen prevalent in myeloma cells. With this therapy the company has established itself as a leader in the field, moving on to new targets that offer exciting potential for the future.

One significant milestone along the way came in 2017, when a collaboration with Legend Biotech (Nasdaq: LEGN) opened up a new front in the area of CAR-T cell therapies.

This led to the establishment of J&J’s first European state-of-the-art facility for the production of CAR-T therapies, in Ghent, Belgium.

In the runup to the 66th American Society of Hematology (ASH) meeting, the therapy area’s most significant medical congress, The Pharma Letter met with two senior leaders from the firm’s European business to discuss progress.

More options available

Reflecting on the strides made in recent years, Dr Edmond Chan notes that the focus on more precise, targeted treatments, such as CAR T-cell therapies and bispecific antibodies, has been a game changer.

“The median overall survival for multiple myeloma has gone from three years to now between eight to ten years, which is a tremendous improvement,” he says, adding: “Now, we will need to make sure that the right patients get the right therapy and maximize the benefit-risk for the individual.”

In the realm of emerging targeted therapies, J&J, along with other companies, have focused their research on new antigens, such as B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5), which show particular promise in multiple myeloma.

Dr Chan explains that with BCMA, one of the newest targets: “we’re able to target particular antigens on the cancer cells and then bring in white cells, using the body’s immune system to kill the cancer.”

While there has been substantial progress, both Dr Chan and his colleague, Mario Klesse, stress ongoing challenges, particularly regarding early diagnosis and the complexity of treatment selection.

Diagnostic delays represent a major hurdle. Mr Klesse says: “Almost a quarter of myeloma patients say that they waited over five months until they got the diagnosis,” underscoring the need for increased awareness and early detection efforts.

And with numerous therapeutic combinations now available, navigating the complexity and making the right treatment selection can be a challenge. This complexity makes informed decision-making among healthcare providers all the more important, balancing efficacy and safety for each individual patient.

Tolerability remains an important focus. As Dr Chan says, “none of the therapies that we offer are without the side effects.” Here, innovative methods of administration could also help, with research showing that subcutaneous formulations could enhance tolerability, improving patient comfort while affording a reduced risk of infusion-related reactions and time spent in hospital.

New endpoints

One major development that could help bring innovation to patients sooner is the adoption of minimal residual disease (MRD) - a measurement of the remaining cancer cells in the body post-treatment - as a surrogate endpoint for overall survival.

In multiple myeloma, achieving MRD negativity, where no trace of cancer is detected, correlates closely with improved long-term outcomes, including progression-free survival and overall survival.

The US regulator now recognizes this as a surrogate endpoint for accelerated approval in multiple myeloma, following a unanimous recommendation from its scientific advisors in April 2024.

Dr Chan says that in future trials, “MRD would be a core, really important outcome, but it will not be the only one.” He adds: “We will be able to demonstrate the efficacy of the new developments faster…and get them approved for patients a lot earlier.”

In one case, J&J was able to demonstrate MRD differences as early as six months into the study, raising the prospect that researchers could “potentially save years” in the development process.

All eyes on ASH

As the 2024 ASH meeting approaches, the multiple myeloma community looks with anticipation for more signs of progress, building on the strong showing from last year.

At last year's meeting, J&J focused on optimizing treatment regimens to develop more convenient and patient-friendly options. This approach is helping to transition away from generalized treatment, which has been marked by cycles of remission and relapse, toward a personalized approach across the care pathway.

Currently, there is a 36% attrition rate from first line to second line treatment, a figure that unfortunately worsens in later stages, as underscored by Dr. Chan. In light of this challenge, taking a more personalized approach has emerged as a crucial component of a paradigm shift towards earlier intervention. This strategy not only aims to address the high attrition rates but also enables the deployment of the most effective treatments in a timely manner, thereby improving patient outcomes throughout their treatment journey.

Looking to the future, J&J remains committed to a vision of achieving a functional cure for multiple myeloma, an outcome which, for Mr Klesse, means that: “the disease is no longer detectable for five or more years.”

The ultimate goal for researchers, which also emphasizes quality of life as a fundamental treatment objective, is to: “transform outcomes for all patients.”

Mr Klesse explains: “as we conduct research, we also look more and more at the quality of life,” adding: “A therapy which doesn't just prolong life but also provides a good quality of life is ultimately the most valuable for patients.”

We are now closer than ever to making multiple myeloma a condition patients can live with, not fight against every day.