Darzalex Faspro moves closer to FDA approval as first therapy for high-risk smoldering multiple myeloma

The U.S. Food and Drug Administration (FDA) is preparing for one of the most closely watched oncology decisions of the year. Darzalex Faspro (daratumumab and hyaluronidase-fihj), developed by Johnson & Johnson’s Janssen Pharmaceutical Companies, has received strong support from the FDA’s Oncologic Drugs Advisory Committee (ODAC) for use in adults with high-risk smoldering multiple myeloma (HR-SMM). If the agency grants full approval, it would mark the first-ever therapeutic option for this precursor stage of myeloma—shifting clinical practice from reactive treatment to proactive intervention.

In May 2025, the ODAC voted 6-2 in favor of Darzalex Faspro, determining that its benefits in delaying disease progression outweigh potential safety risks. The recommendation followed submission of a supplemental biologics license application in late 2024, and the FDA’s final decision is expected before the end of the year. For now, clinicians and investors are watching closely, aware that this single approval could redefine how early cancer states are treated across hematology and beyond.

Why the FDA panel’s endorsement signals a potential paradigm shift in smoldering myeloma care

High-risk smoldering multiple myeloma occupies a clinical gray area—neither benign nor fully malignant. These patients harbor measurable plasma-cell proliferation and genomic abnormalities but lack symptoms or organ damage. Historically, doctors have opted for surveillance, fearing overtreatment in those who might never progress. Yet for high-risk individuals, nearly half develop active myeloma within two to three years.

The FDA panel’s vote represents a decisive challenge to that long-standing “watch-and-wait” model. By favoring Darzalex Faspro, regulators signaled openness to earlier intervention in cancers once considered untreatable until advanced. The subcutaneous injection combines daratumumab, a CD38-targeting monoclonal antibody, with hyaluronidase to speed absorption, allowing administration in minutes instead of hours. This streamlined format could make maintenance-style therapy more acceptable for patients who otherwise feel healthy.

For oncologists, the shift could be transformative: treating smoldering disease before irreversible marrow damage occurs may preserve long-term immune function and delay the need for intensive chemotherapy or stem-cell transplantation. It also positions early myeloma alongside other cancers—such as breast and colorectal—where pre-emptive therapy has become standard practice.

How the AQUILA Phase 3 trial convinced regulators that early intervention could delay progression

The Phase 3 AQUILA trial (NCT03301220) provided the clinical foundation for Darzalex Faspro’s regulatory review. Conducted across 20 countries, the randomized study enrolled nearly 400 patients diagnosed with high-risk smoldering multiple myeloma and assigned them to either Darzalex Faspro monotherapy or active observation.

After a median follow-up exceeding five years, the results were striking. Patients receiving Darzalex Faspro achieved a 51 percent reduction in risk of progression to active myeloma or death compared with observation (hazard ratio 0.49; P < 0.0001). Median progression-free survival was not reached in the Darzalex group versus 41.5 months in the observation arm—suggesting that many remained disease-free for more than half a decade.

Adverse events were manageable and largely mild, consisting primarily of upper respiratory infections, fatigue, and injection-site reactions. Importantly, the subcutaneous regimen avoided many infusion-related complications associated with intravenous daratumumab, making long-term therapy more feasible.

The FDA’s reviewers acknowledged that progression-free survival is not a direct measure of overall survival but nonetheless called the data “clinically meaningful.” The agency’s ongoing deliberations are focused on whether early disease modification justifies approval when patients remain asymptomatic. If cleared, it would establish a precedent for treating latent oncologic conditions where biomarkers predict near-certain progression.

What analysts expect from Johnson & Johnson’s oncology portfolio if approval becomes reality

From a market perspective, Darzalex Faspro’s expansion into the HR-SMM indication could be one of Johnson & Johnson’s most consequential oncology wins since the original Darzalex launch in 2015. The therapy generated approximately $8.4 billion in global sales last year, making it the top-selling multiple myeloma drug worldwide. Analysts estimate that adding the smoldering indication could increase annual revenue by $500 million to $700 million within the first three years of launch.

Financial analysts at several brokerages have noted that the FDA’s positive tone on early intervention strengthens Johnson & Johnson’s overall hematology strategy. Alongside Darzalex Faspro, the company’s newer bispecific antibodies—teclistamab (Tecvayli®) and talquetamab (Talvey®)—are being positioned across the disease continuum, enabling Janssen to dominate both early and late-stage myeloma markets.

Investor sentiment toward Johnson & Johnson’s oncology division has turned bullish since the ODAC vote. Shares rose modestly following the May announcement, reflecting expectations that Darzalex Faspro could capture an entirely new patient population previously managed only through monitoring. Analysts also argue that this approval could soften revenue erosion from biosimilar encroachment on older oncology drugs.

Why the FDA’s decision could reshape global oncology policy and redefine how cancer prevention is regulated

Beyond its commercial value, the pending decision has broader policy implications. If the FDA approves Darzalex Faspro based on its ability to delay progression rather than extend survival, it would signal a new willingness to recognize time-to-progression as a standalone endpoint for approval in early cancer settings.

This paradigm could influence regulatory frameworks worldwide, particularly in the European Union, Japan, and Canada, where health authorities are simultaneously reviewing the same dataset. The European Medicines Agency (EMA) has already accepted Janssen’s application, and parallel guidance from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) is expected by mid-2026.

Health-economics experts are also evaluating whether preventive oncology drugs can reduce downstream costs associated with late-stage treatment. Darzalex Faspro’s once-monthly maintenance schedule could reduce hospital stays and transfusion rates—potentially offsetting drug costs. However, payers remain cautious, noting that long-term adherence and diagnostic accuracy in defining “high-risk” patients will determine value outcomes.

Should approval occur, this would likely prompt updates to the National Comprehensive Cancer Network (NCCN) guidelines and new educational programs to help community oncologists identify HR-SMM more precisely. Such ripple effects could extend to research in monoclonal gammopathy of undetermined significance (MGUS) and other pre-cancerous hematologic conditions.

How experts believe Darzalex Faspro could transform early myeloma treatment strategy and reshape investor confidence

Industry experts and clinical researchers have characterized the ODAC vote as both a scientific milestone and a philosophical shift in how oncology defines “disease.” If the FDA finalizes approval, Darzalex Faspro could become the first therapy to formally treat a pre-cancerous hematologic condition, legitimizing early intervention as a strategy for long-term remission.

Clinicians interviewed by oncology journals suggested that this model might one day resemble preventive cardiology—where risk factors, not symptoms, trigger intervention. They added that patient psychology also plays a role: being treated rather than “watched” can offer reassurance and reduce anxiety associated with disease monitoring.

From a capital-markets perspective, the move has already boosted investor optimism around Johnson & Johnson’s R&D pipeline. The company’s emphasis on immunotherapy, paired with its diversification into cell-based and bispecific platforms, has convinced analysts that its hematology segment remains a durable growth driver through the next decade.

Still, experts warn that post-marketing surveillance will be critical. As Darzalex Faspro enters a largely asymptomatic population, regulators will monitor for cumulative toxicity and immune suppression over multi-year use. Success in this indication would also intensify competition, spurring rival drugmakers such as Bristol Myers Squibb and Regeneron to pursue their own early-stage myeloma programs.

If the FDA grants approval in 2025, Darzalex Faspro will not just expand Janssen’s oncology footprint—it will rewrite how both physicians and regulators think about the earliest steps of cancer progression. The boundary between prevention and treatment, long viewed as separate, could finally blur into a single continuum of care.