The commercial was called “Clarity.” The FDA’s untitled letter made clear the name was aspirational. BeOne Medicines USA, Inc. — the U.S. subsidiary of the Chinese oncology firm formerly known as BeiGene — produced a direct-to-consumer broadcast television advertisement for Brukinsa (zanubrutinib), its BTK inhibitor approved for Waldenström’s macroglobulinemia and several other B-cell malignancies. The FDA’s Office of Prescription Drug Promotion reviewed the ad — designated internally as 0525-BRU-PRC-137 — and found that its “compelling and attention-grabbing visuals” created net impressions that the clinical data could not support. The agency issued its untitled letter. What does that mean for a company that has now received at least three OPDP enforcement actions in under 18 months?
That number is not a rhetorical flourish. It is the operational record.
Three Strikes, One Pattern
To understand what went wrong with “Clarity,” you need to run the timeline backward. Brukinsa received FDA approval on August 31, 2021, initially for Waldenström’s macroglobulinemia based on data from the Phase 3 ASPEN trial. The ASPEN trial enrolled 201 patients in its primary cohort — patients with MYD88 L265P-mutant WM — and at a median follow-up of 44.4 months, zanubrutinib demonstrated durable responses versus ibrutinib. The efficacy data was real. The science held up. What didn’t hold up was how BeOne chose to represent that science on television.
The “Clarity” ad used visual storytelling — the kind of craft that a DTC agency charges premium rates to produce — to generate impressions of efficacy that exceeded what the prescribing information actually supports. The FDA’s OPDP doesn’t pull punches in its untitled letters. When the agency writes “misleading suggestions,” it means the ad created a false belief in the mind of a reasonable patient viewer, and that false belief was driven by what they saw rather than what was technically said. That is a sophisticated failure. It requires resources, a production budget, and multiple rounds of internal review — none of which caught it.
But the “Clarity” letter does not stand alone. On December 15, 2025, the FDA issued a separate untitled letter to BeOne Medicines USA over two Microsoft Teams branded backgrounds promoting TEVIMBRA (tislelizumab-jsgr), its PD-1 inhibitor. The agency found those materials false or misleading. That was a different drug, a different format, and a different promotional channel — and the same underlying failure: promotional content that outran regulatory review. Three enforcement letters across two drugs and multiple channels in 18 months is not bad luck. It is an organizational posture toward promotional compliance.
What the Pre-Clearance Gap Actually Costs
Here is the counterintuitive read on pharmaceutical DTC advertising that most compliance discussions avoid: the FDA does not require sponsors to submit broadcast television advertisements for pre-approval review. The OPDP voluntary submission program exists, but it is exactly what it sounds like — voluntary. A sponsor can produce a $4 million television campaign, run it nationally, and the FDA sees it only after a viewer or competitor files a complaint, or after OPDP’s own surveillance catches it. By the time the untitled letter arrives, the misleading impression has already landed in the living rooms of patients who are, in many cases, living with blood cancer and actively looking for treatment options.
BeOne’s situation illustrates precisely how that gap functions in practice. OPDP issued only five enforcement letters total in 2023, and five untitled letters and no warning letters through December 2024. In a landscape where the agency’s entire annual enforcement output fits on a single page, being named twice — across different drugs, different formats, different calendar years — signals something the company’s regulatory affairs leadership needs to answer for internally. An untitled letter carries no financial penalty. It does not trigger a clinical hold. It does not pause approval. What it does is sit in the public record as evidence that a sponsor’s promotional review process produced content the FDA found misleading and felt compelled to correct by name.
The FDA’s 2024 final rule on DTC television advertisements tightened requirements around how major statements — the fast-talking risk recitation at the end of every broadcast pharmaceutical ad — must be presented clearly, conspicuously, and neutrally. That rule addressed audio and visual distractors that undermine risk communication. The “Clarity” enforcement action suggests BeOne’s production team and its agency either missed the implication of that regulatory signal or chose to absorb the risk. Neither reads well for a company trying to compete against AstraZeneca’s Calquence and Janssen’s Imbruvica in the crowded BTK inhibitor market.
The Operational Rot the Letter Doesn’t Name
An untitled letter names the ad. It does not name the internal review chain that approved it. Somewhere between the creative brief and the broadcast buy, a regulatory reviewer — or more likely a committee of them — signed off on “Clarity.” That person, or that committee, watched the same attention-grabbing visuals the FDA later found misleading and determined they were acceptable. Which means either BeOne’s promotional review SOP does not require a systematic net-impression analysis for broadcast content, or the SOP exists and was not applied rigorously, or it was applied and someone overrode the concern. All three explanations point to the same structural problem: the compliance function was subordinated to the commercial function at the moment of decision.
This is the pattern that makes BTK inhibitor promotion particularly fraught. Brukinsa is competing against deeply entrenched brands in an indication where oncologists already have established prescribing habits and patients are seeking information actively. The commercial pressure to produce emotionally resonant DTC content is intense. Visuals that convey clarity, confidence, and normalcy in the face of a blood cancer diagnosis are exactly what a marketing team is incentivized to produce. The problem surfaces when those visuals — a patient looking vibrant, a doctor looking certain, a treatment looking uncomplicated — create an impression of efficacy or risk that the clinical data behind the label does not fully warrant. The ASPEN trial showed a very good drug. The “Clarity” ad apparently showed something better than that.
For sponsors running post-approval promotional programs at scale, the lesson from BeOne’s record is specific: net-impression review for broadcast content requires independent regulatory sign-off that sits outside the brand team’s chain of command. Build a vendor-quality metric into every DTC production approval gate before the media buy gets authorized — not after the FDA issues a letter. For site directors and investigators who field patient questions about drugs they’ve seen advertised on television, the BeOne “Clarity” situation is a reminder that what a patient believes going into an informed consent conversation may have been shaped by a TV spot the FDA later found misleading. That is an operational problem as much as a regulatory one.
Watch for whether OPDP follows this untitled letter with escalating action — the agency has the authority to issue warning letters, demand corrective advertising, and refer egregious cases for further enforcement. Three letters in 18 months from a single sponsor is the kind of pattern that moves from the inbox of a promotional reviewer to the desk of a division director. BeOne’s next DTC submission to OPDP’s voluntary review queue will tell you whether the company has actually changed its internal posture — or is simply waiting to see what the agency does next.
References
- FiercePharma — “BeOne Medicines’ Brukinsa TV ad ‘Clarity’ hit by FDA over ‘misleading suggestions'”
- FDA OPDP — Untitled Letter to BeOne Medicines USA, Inc. re: Brukinsa TV advertisement (0525-BRU-PRC-137)
- FDA OPDP — Untitled Letter to BeOne Medicines USA, Inc. re: TEVIMBRA Microsoft Teams backgrounds (December 15, 2025)
- FDA — Brukinsa (zanubrutinib) Approval for Waldenström’s Macroglobulinemia (August 31, 2021)
- Journal of Clinical Oncology — Final Analysis of the Phase III ASPEN Study: Zanubrutinib vs. Ibrutinib in Waldenström Macroglobulinemia
- Juris Law Group — FDA OPDP Enforcement Letter Counts, 2023–2024
- FDA — Office of Prescription Drug Promotion (OPDP): Voluntary Submission Program
- Venable LLP — FDA’s 2024 Final Rule on DTC Television Advertisements: Major Statement Requirements
Moe Alsumidaie, MBA, MSF, is founder and Chief Editor of Vanguard Publications, which publishes Clinical Trial Vanguard, Pharma Vanguard and BullScope, and Head of Research at CliniBiz. He has two decades in clinical trial operations and data science, with earlier roles at Genentech, Abbott Vascular and Stanford University Medical Center, and is a guest lecturer in clinical trial sciences at Rutgers University.
