Drug development is often described as “a path where failure is more familiar than success.” In particular, clinical trial design aligned with global standards and communication with overseas regulatory authorities remain among the biggest challenges faced by our companies. To address this need, <The Bio> is launching a new expert column by Hanlim Moon, CEO of MediRama. Dr. Moon is a veteran who has spent decades in global big pharma, experiencing the entire process of oncology drug development and directly navigating the thresholds of leading regulatory agencies. As a physician-scientist and clinical strategist, his deep insights will serve as a guideline for our companies striving to cross the “valley of death” between nonclinical and clinical stages. This monthly column will function as a “practical strategy guide,” covering not only key approaches at each stage of drug development but also analyses of review trends among overseas regulatory authorities. It is highly recommended reading for professionals in the pharmaceutical and biotech industries aiming at the global market.[Editor’s note]

Multiple myeloma (MM) treatment is one of the oncology fields that has undergone the most dramatic advancements over the past 20 years. Moving beyond an era that relied on alkylating agent–based chemotherapy, the current paradigm is centered on targeted and immunotherapies. This transformation has not only significantly improved survival rates but has also expanded treatment goals from simple disease control to deep response, long-term disease management, and ultimately, functional cure.
At the center of this innovation lies the contribution of companies that have systematically translated scientific advances into structured treatment strategies, with Johnson & Johnson (J&J) being recognized as a key player that has led the evolution of multiple myeloma treatment.

1. Establishing the Treatment Backbone: Paradigm Shift with Velcade (bortezomib)

J&J’s leadership in multiple myeloma began with a meticulously designed strategy that combined the innovative drug Velcade (bortezomib) with its DAS (Disease Area Stronghold) strategy. The DAS strategy is a business model that goes beyond a single drug to dominate the treatment standard and ecosystem of a specific disease area, thereby establishing unmatched expertise—in essence, building an unassailable “stronghold” in that therapeutic domain.

By introducing the proteasome inhibitor developed by Millennium into the global market, J&J created a decisive turning point that shifted conventional chemotherapy toward “mechanism-based therapy.” In particular, the VRd regimen established around Velcade became a robust combination backbone for modern multiple myeloma treatment. As numerous subsequent therapies have been developed by adding onto this backbone, J&J has positioned itself not merely as a supplier of therapeutics but as a designer of treatment standards.

2. Integration of Immunotherapy: Reshaping the Treatment Framework with Daratumumab (Darzalex)

The next wave of innovation came with the emergence of the CD38 monoclonal antibody daratumumab. Daratumumab transformed the treatment paradigm into the “era of antibody-based and quadruplet regimens.”

In the MAIA study, the daratumumab-based combination (Dara-Rd) achieved an overall response rate (ORR) of 93% and reduced the risk of progression (PFS hazard ratio of 0.56), corresponding to a 44% reduction in relapse risk compared to the control group. Furthermore, in the PERSEUS study, the Dara-VRd quadruplet regimen demonstrated an ORR exceeding 95% and a 4-year PFS rate of 84%, shifting the treatment goal toward “how deep the response is (MRD negativity).” This success firmly established the efficacy of antibody therapeutics in the market and served as a key milestone for followers, including Sanofi with its development of isatuximab.

3. Teclistamab: Expanding Immunotherapy in the BCMA Era and Advancing into Standard of Care

The frontline of multiple myeloma treatment is now being reshaped around BCMA-targeted therapies, with J&J’s teclistamab demonstrating strong scalability and efficacy at the center of this transformation.

• Innovation of “off-the-shelf” therapy: Despite the strong efficacy of CAR-T therapies, their complex autologous cell manufacturing process and delays represent inherent limitations. In contrast, teclistamab, as an “off-the-shelf” therapy available for immediate administration, provides unparalleled accessibility in clinical practice and lowers the barrier to T-cell redirection therapies.
• Clinical leap in MajesTEC-3: Teclistamab-based combination therapy demonstrated remarkable results, with an approximately 89% response rate and a PFS hazard ratio reduced to 0.17. Notably, maintaining a PFS rate above 89% at 48 months is comparable to or even exceeds outcomes seen with CAR-T therapies, suggesting that bispecific antibody therapy is a powerful tool toward achieving cure.
• Expansion into maintenance and first-line therapy: Teclistamab is now extending beyond later lines of therapy into earlier stages, including maintenance settings. Ongoing strategic studies are evaluating its combination with lenalidomide following autologous stem cell transplantation (ASCT) to continuously control minimal residual disease (MRD), thereby preventing relapse and promoting long-term survival.

4. Talquetamab: Strategic Value of GPRC5D Targeting and Advancement into First-Line Therapy

Beyond BCMA, J&J has diversified its targeting strategy by developing talquetamab, which targets the novel antigen GPRC5D. This provides a strong alternative for patients who relapse after or develop resistance to BCMA-targeted therapies, further reinforcing the “stronghold.”

• Mechanistic differentiation: By targeting GPRC5D, which has a different expression pattern from BCMA, talquetamab helps overcome tumor immune escape. In the MonumenTAL-1 study, it demonstrated strong efficacy with an approximate 74% response rate.
• First-line integration strategy: Through the MajesTEC-7 study, J&J is advancing both teclistamab (Tec-DR) and talquetamab (Tal-DR) into the first-line setting simultaneously. This reflects the core of the DAS strategy—establishing a comprehensive stronghold from the earliest stage of diagnosis using multi-target approaches (BCMA and GPRC5D).

5. Carvykti and the Completion of the Continuum of Care

J&J’s true strength lies in its establishment of a “continuum of care” that spans the entire patient journey—from diagnosis to relapse and refractory disease.

• Velcade: Establishment of the standard backbone and foundation of the stronghold
• Daratumumab: Integration of immunotherapy into standard care and the opening of the quadruplet era
• Carvykti: Achieving deep remission with top-tier efficacy (efficacy ceiling)
• Teclistamab & Talquetamab: Providing immediate immunotherapy options across treatment lines through target diversification and accessibility

This vertically integrated lineup provides clinicians with the flexibility to tailor optimal treatment choices based on a patient’s genetic characteristics and prior treatment history.

6. Conclusion: The Final Stretch Toward Cure

Multiple myeloma treatment has evolved from backbone-centered approaches to immunologic redirection. At each inflection point, J&J has delivered creative and innovative solutions, establishing itself not merely as a supplier of drugs but as a “designer of the treatment ecosystem.” Through continuous R&D and strategic insight, multiple myeloma is now transforming from a disease that can be managed long-term into one where cure is a realistic goal. J&J’s leadership at the forefront of this innovation will continue to serve as a source of hope for patients and a reliable benchmark for clinicians.

Source: The Bio (https://www.thebionews.net)