CASE AUTH/3903/5/24 NO BREACH OF THE CODE
COMPLAINANT v GSK
Allegation regarding Blenrep promotional website
CASE SUMMARY
This case was in relation to a safety claim which appeared on a GSK promotional website aimed at UK health professionals. The complainant alleged that the claim, which appeared on the homepage of the Blenrep section of the website, and included the wording “generally well tolerated and manageable safety profile”, was inaccurate, misleading and unqualified.
The outcome under the 2021 Code was:
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No Breach of Clause 5.1
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No Breach of Clause 6.1
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No Breach of Clause 6.2
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This summary is not intended to be read in isolation.
For full details, please see the full case report below.
FULL CASE REPORT
A complaint about GSK was received from an anonymous, contactable complainant who described themselves as a health professional.
The complainant later became non-contactable.
COMPLAINT
The complaint wording is reproduced below with some typographical errors corrected:
“A safety claim on the Blenrep promotional webpage is not accurate and downplays safety elements and safety data related to the drug. The claim is located on [link provided]. In the middle of the page there is a section about the DREAMM-2 clinical trial and below that text are 3 green boxes focused on efficacy, safety, dosing and administration. Under the safety box, there is a claim which reads ''Blenrep had a generally well tolerated and manageable safety profile.'' However, the DREAMM- 2 trial actually had 5% of patients discontinue the drug due to serious eye related side effects. Therefore, the claim is inaccurate to specify that drug adverse events had a manageable safety profile and were generally well tolerated when in fact the drug had to be stopped due to serious eye side effects. The information about the 5% discontinuation was not qualified alongside such a bold claim on safety. Furthermore, Blenrep is a black triangle product with the summary of product characteristics discussing the need to stop Blenrep if there are serious infusion related reactions and therefore a broad claim that there is a manageable safety profile is not accurate when discontinuation is needed for certain side effects. The claim is in breach of clauses 6.1, 6.2, 5.2 and 2. Request PMCPA to investigate such a claim.”
When considering the complaint, the case preparation manager noted that the complainant had cited Clause 5.2. The case preparation manager wrote to the complainant to request further information to provide an allegation relating to this clause, but received no response. The case preparation manager therefore informed the complainant that the company would not be asked to respond to Clause 5.2.
When writing to GSK, the case preparation manager asked it to consider the requirements of Clauses 2, 6.1 and 6.2 as cited by the complainant. The company was also asked to consider Clause 5.1 of the 2021 Code.
GSK’S RESPONSE
The response from GSK is reproduced below:
“GSK was extremely disappointed to have received a letter dated 11th June 2024 from the PMCPA informing us of a complaint from an individual describing themselves as an anonymous healthcare professional regarding the above. The PMCPA has asked us to consider clauses 6.1, 6.2, 5.1 and 2 of the 2021 ABPI Code of Practice (the Code).
The complainant alleges that the promotional webpage PM-GB-BLM-WCNT-220010 (V5.0) has a safety profile claim that is inaccurate and has breached clauses 6.1, 6.2, 5.1 and 2 of the Code.
GSK takes its responsibility to abide by the letter and the spirit of the Code and all other relevant UK rules and regulations very seriously. Following the complaint, we have temporarily taken down the relevant webpages to review the materials in question, as well as review our internal ways of working. Following our review, GSK is comfortable that both our processes and the materials in question are of suitable quality and of a high standard and are therefore in line with the Code. Consequently, we refute breaches of clauses 6.1, 6.2, 5.1 and 2 of the Code.
GSK has laid out the specific responses to the individual clauses the PMCPA has asked us to consider in detail below.
Website background
The Blenrep▼(belantamab mafodotin) webpages referred to in the complaint are part of a more extensive promotional website called GSKPro, for UK Healthcare Professionals (HCPs) only. The website contains promotional information about all GSK medicinal products currently marketed in the UK. Within the website there is a section dedicated entirely to the product Blenrep.
The Blenrep website can be accessed by three methods:
· Direct access by HCPs via a search engine, such as Google, that requires confirmation that they are an HCP via a pop up, as opposed to a member of the public for whom there is a link to a separate part of the website with relevant content.
· Via third party emails sent by Cogora who send emails to HCPs who have given their prior consent to receive emails from pharmaceutical companies via the Cogora platform.
· Direct promotion from GSK via email, sending promotional emails to HCPs who have given their consent to receive these.
GSK processes and structure
GSK has robust processes and structures for material approval to ensure compliance with the Code, GSK’s own code, and UK regulations. All employees involved in copy approval must complete mandatory GSK copy approval SOP training . Each brand team holds a regular forum for decision and agreement (FDA), involving medical and commercial teams, to discuss and align on materials requiring copy approval, to align fully and ensure Code-compliant content. Where views differ, such as those over specific claims, there is a clear and well-established route of escalation for resolution.
To maintain ongoing Code knowledge, GSK conducts a monthly Code Forum meeting in which Code cases are presented and discussed as well as any other compliance/ governance issues which merit awareness. While the meeting is intended principally for all medical signatories, commercial reviewers, and content owners, other staff interested to attend for their own learning and development may do so. Attendance is consistently strong, and materials discussed are stored on GSK’s internal governance platform, accessible to all UK employees.
Additionally, GSK holds Governance meetings once a month for medical signatories and medical reviewers. Attendees raise Code-related agenda items for discussion, with a view to reaching consensus within the group, under the guidance of experienced senior signatories.
Furthermore, GSK has a fair and objective process for assessing and validating not only medical signatories, but also commercial reviewers. The role of the commercial reviewer is to provide commercial overview of all promotional and relevant non-promotional materials for appropriateness, including fundamental aspects and principles of the Code, as well as content suitability and strategic alignment. These assessments involve one, or more often two assessors, objectively questioning the candidate on case examples, covering multiple aspects of the Code. In addition, the appraisee must have completed a set of mandatory training requirements. In the case of medical signatories, the appraisee must have been mentored for a period by another experienced medical signatory, until the mentor deems the appraisee ready to take the assessment to become a final medical signatory.
Blenrep and disease background
Blenrep, a first‐in‐class, B‐cell maturation antigen (BCMA)‐binding antibody‐drug conjugate (ADC) containing monomethyl auristatin F (MMAF),7 eliminates myeloma cells by a multimodal mechanism involving direct cell killing and activation of anti‐myeloma immune responses. Blenrep is indicated as fifth line (5L+) monotherapy for relapsed refractory multiple myeloma (RRMM) patients who have received at least four prior lines of therapy and whose disease is triple-class refractory, indicating progression on the last therapy.
Clause 6.1
The complainant alleges that in the webpage PM-GB-BLM-WCNT-220010, the claim ‘Blenrep had a generally well tolerated and manageable safety profile’ is inaccurate. According to the complainant, ‘DREAMM-2 trial actually had 5% of patients discontinue the drug due to serious eye related side effects’. Consequently, the complainant contends that this constitutes a breach of Clause 6.1.
It is not feasible to directly compare different products’ eye related discontinuation rates, as in the RRMM treatment pathway eye-related side effects are specific to Blenrep. However, it is important to consider it in the wider context of medication discontinuation rates due to Adverse Events (AE) in RRMM. We have focused on NICE-approved options in the 5L+ setting to align with Blenrep’s licence and UK patient access. Below is a table summarising some of the discontinuation rates due to adverse events in trials for medications available to the National Health Service England (NHSE) in the 5L+ setting:
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RRMM trial
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Licensed RRMM Medication
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Medication discontinuation rates due to any AE*
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PANORAMA 3 trial
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Panobinostat
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30%, 28% and 15%
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MagnetisMM-3 trial
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Elranatamab
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13.8%
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MM-003 trial
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Pomalidomide
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4% and 6%
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STORM trial
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Selinexor
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18%
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DREAMM-2 trial
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Blenrep
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8% and 10%
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* Where there are multiple percentage stated, each value represents a discontinuation rate based on different dosing schedules of the same medicine
Although direct comparisons are not available, nonetheless the 5% Blenrep discontinuation rate for eye related side effects in the DREAMM-2 trial cited by the complainant is clearly lower and consistent with the claim that Blenrep is generally well tolerated by such patients who, unfortunately have already failed to respond to several prior lines of treatment.
Furthermore, the complainant’s assertion, that if a medication is discontinued due to an AE then it cannot be manageable, is incorrect. Standard clinical management of AEs, especially in Oncology invariably includes dose reduction, omission of dosage and discontinuation of medication. Thus, discontinuation of medication as part of a management strategy is a well-established practice not only in clinical oncology but in all other therapy areas. As seen in Journal of Clinical Medication, management of adverse events in patients treated with BCMA-targeting therapies (Blenrep and other products) includes dose modification, supportive care, and when appropriate, discontinuation of therapy.
While the complainant notes that the SmPC discusses ‘the need to stop Blenrep if there are serious infusion-related reactions (IRRs)’ and therefore, in their words, ‘manageable safety profile is not accurate’, it is important that the SmPC requirements are considered in the context of the overall IRR safety profile. As the DREAMM-2 trial demonstrated clearly, most Blenrep IRRs were Grade 1-2, self-limiting, and resolved within the same day. While 3% of patients experienced Grade 3 IRRs, notably, no Grade 4 or 5 IRRs were reported. Published data for daratumumab, the most commonly UK prescribed monoclonal antibody for multiple myeloma, reported at least double the IRR rates:
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Medication
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Trial
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IRR rates, %
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Grade 1 – 2
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Grade 3
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Total
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Blenrep
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DREAMM-2
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18%
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3%
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21%
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Daratumumab
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CASTOR
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36.7%
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8.6%
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45.3%
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POLLUX
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42.4%
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5.3%
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47.7%
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In fact, Blenrep's lower incidence and severity of IRRs means that its SmPC does not require pre-medication before the first dose. This contrasts with daratumumab, whose SmPC states, "Patients should be pre-medicated with antihistamines, antipyretics, and corticosteroids to reduce the risk of IRRs prior to treatment with DARZALEX". Thus, while discontinuation of Blenrep may be clinically appropriate in rare cases of serious IRRs, the overall incidence and severity of such reactions is low, supporting the claim that Blenrep has a ‘generally well tolerated and manageable safety profile’.
It is also crucial to highlight that stopping or reducing the rate of infusion in cases of IRRs is standard practice for all infused treatments. Clinicians manage this daily, and it is an entirely normal clinical practice. Equating the cessation of infusion with negating a 'manageable safety profile' is not accurate. In fact, it would be indefensible from a Medical Negligence perspective not to manage infusions in this way. Managing risks that arise clinically is standard Medical Practice and is extremely common and necessary when prescribing infused treatments in oncology and other non-oncological therapy areas.
GSK also contends that while the claim in question can stand alone, it is accompanied by a tab to “view safety data”, which directs the HCP to another webpage dedicated entirely to the detailed safety information for Blenrep. This resource provided further relevant information for Blenrep , including detailed safety information. This prominent link, positioned immediately below the disputed claim, illustrates GSK’s commitment to facilitate specialist haemato-oncologists’ access to comprehensive safety (and efficacy) data, thereby supporting the informed, rational use of an important medicinal product licensed for the specialist management of a serious and refractory haematological malignancy.
In summary, GSK disagrees strongly with the complainant’s assertion that clinical consideration and/ or a decision to discontinue treatment with Blenrep is not part of well-established patient management strategy. HCPs are required routinely to respond to adverse events and / or drug-related unwanted side-effects. As detailed above, managing complex therapeutic decisions encompasses a spectrum of possible actions balancing the effectiveness of a treatment with the severity of any side effects that may arise. An appropriate and routinely employed option is to discontinue some or all of a treatment regimen. That Blenrep has a ‘generally well tolerated and manageable safety profile’ is wholly consistent with such an approach, the product’s marketing authorisation, its SmPC and clinical consensus from relevant, experienced Healthcare Professionals who prescribe Blenrep and manage patients’ therapeutic response accordingly.
Consequently, GSK maintains that the claim is accurate, balanced, fair, and reflects current evidence on adverse events for the product and their management. For these reasons, we disagree that the Company is in breach of Clause 6.1.
Clause 6.2
The complainant alleges a breach of Clause 6.2 regarding "Blenrep had a generally well tolerated and manageable safety profile" on PM-GB-BLM-WCNT-220010, claiming that the statement is incapable of substantiation. GSK strongly disagrees. As detailed in our Clause 6.1 response, this claim is supported by clinical data from the DREAMM-2 trial and comparative analysis with other RRMM treatments. In addition to the evidence presented in our Clause 6.1 response, we would like to highlight further substantiation.
An important aspect of evaluating a drug's tolerability, aside from discontinuation rates, is its impact on patients' Quality of Life (QoL). Patient Reported Outcomes (PRO) from the DREAMM-2 trial indicated that while on Blenrep treatment, overall QoL, Physical Functioning, and Role Functioning were maintained. This includes patients experiencing eye and vision related symptoms. This is a significant outcome for patients with triple class RRMM as discussed previously due to its high degree of disease burden.
The DREAMM-2 PRO study report confirmed that no patients had permanent, severe vision changes or loss of vision in either eye. The manageable nature of eye-related side effects was further supported by the fact that eye symptoms improved over time. Median time to recovery ranged from 23.5 to 44.0 days , indicating that eye related side effects are reversible and manageable.
Compared to other therapies that also target BCMA, Blenrep safety profile is tolerable and manageable. For instance, teclistamab, a bispecific antibody (BsAb) that targets BCMA, was studied in the MajesTEC-1 trial for the treatment of triple refractory MM patients.
In this trial, infections were reported in 76.4% of patients receiving teclistamab, with grade 3 or 4 infections occurring in 44.8% of cases. The DREAMM-2 trial demonstrated a lower overall infection rate of 45% when Blenrep is prescribed at its licensed dose at, with grade 3 or 4 infections occurring at 20%. This is consistent with an independent study conducted at Memorial Sloan Kettering Cancer Centre to compare infectious complications in patients receiving BCMA-targeting therapies. The study observed a lower risk for severe infections in a similar patient population treated with BCMA-directed ADCs (Blenrep). The incidence of severe infections was higher with BsAb (40%) than ADC (8%), including grade 5 (leading to death) infections (7% vs 0%, respectively).
Other BCMA-targeting agents have also reported significant risks such as cytokine release syndrome (CRS), a supraphysiologic inflammatory response of the immune system, and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS can manifest as a range of symptoms from headaches, confusion, and somnolence to severe, life-threatening conditions, including seizures, cerebral oedema, and comatose states. In instances of grade ≥2 CRS and any grade ICANS, it is recommended that patients be transferred to the Intensive Care Unit (ICU) for appropriate management. In support of its tolerable and manageable safety profile and unlike other BCMA targeting agents, Blenrep does not require inpatient admission for administration and monitoring or ICU adverse event management.
Peer-reviewed publications and manuscripts by oncology experts in high impact journals further support the substantiation of this claim:
· ‘Single agent belantamab mafodotin shows anti-myeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma.’ – Lancet Oncology 2020 by Dr Lonial et al.
‘At the median 12.4-month follow-up, 3% of patients had discontinued belantamab mafodotin because of corneal events, suggesting that these events were adequately managed with dose modifications (reduction and/or dose delay) and generally tolerated.’ – J Adv Pract Oncology 2023 by Popat et al.
It is also relevant to consider and acknowledge the nature of underlying diseases requiring oncological treatments where the risk-benefit ratio may, of necessity differ from other less aggressive medical conditions. This has already been acknowledged by the PMCPA in a previous Code case of an anonymous oncologist v Pierre Fabre (AUTH/2799/10/15). In that ruling, the Panel: ‘...noted the highly specialised therapy area … In the Panel’s view the audience would be familiar with the side effect profile of cytotoxic medicines generally.’ Oncology treatments that are life prolonging and/or reduce disease relapses can be associated with severe adverse reactions that may be unavoidable. Consequently, what is deemed manageable and tolerable within the oncology community often differ from clinical perspectives in other specialty areas.
As a result, GSK is comfortable that the claim, aligning as it does with clinical trial results and the experience of haemato-oncologists (to whom the webpage is directed) remains valid. The claim queried by the complainant was presented appropriately and supported by relevant citations thereby countering the allegation that it was not capable of the substantiation required by the Code.
For these reasons, we disagree wholly with the Complainant that there has been any breach of clause 6.2.
Clause 5.1
As discussed earlier, GSK processes, training, governance and management monitoring have all been designed and implemented to embed the spirit as well as the letter for the Code. GSK’s standards promote rigour when creating, reviewing, approving and certifying promotional materials. We remain confident that the certification process and the quality of the cited materials are robust. All claims and content including the safety claims raised by the complainant, were critically appraised, deemed correct and suitable thereby meeting the high standards required by the Code.
Consequently, GSK maintains that high standards were maintained and there has not been a breach of Clause 5.1.
Clause 2
The PMCPA also asked GSK to consider Clause 2 of the Code. GSK notes that a ruling of a breach of Clause 2 is a sign of censure, reserved for circumstances that include prejudicing patient safety and/or public health. It is ruled when significant failings have been identified, that include inter alia a risk to patient safety.
In responding to the breaches alleged by the complainant, GSK has argued cogently that there is no evidence of a risk to patient safety, or a failure in the Company’s systems and processes. The webpage in question was reviewed, certified and the final form examined in the manner required and to the standards mandated by the Code and by GSK’s own SOP. Furthermore, GSK has demonstrated that the claim at issue is fully supported and is substantiated by clinical evidence described above. It would not cause confusion. GSK takes patient safety very seriously. We believe strongly that patient safety has not been nor will be prejudiced by the materials and claim in question.
For these reasons, and all others detailed above, GSK’s activities and materials do not risk bringing discredit upon or reducing confidence in the pharmaceutical industry. Consequently, GSK does not recognise that there has been a possible breach of Clause 2.
Additional information
The signatory who reviewed, approved, and certified the material at issue in AUTH/3903/5/24 is a registered UK pharmacist with [X] years’ signatory experience. [Signatory’s previous experience].
Summary
GSK takes its responsibility of abiding by the letter and the spirit of the Code extremely seriously. As laid out in our detailed response above, GSK denies breaches of clauses 6.1, 6.2, 5.1 and 2 of the 2021 ABPI Code of Practice.”
PANEL RULING
This complaint concerned a safety claim on a GSK promotional website for Blenrep. Blenrep is an antibody-drug conjugate which, at the time of the complaint, was indicated as fifth line (5L+) monotherapy for relapsed refractory multiple myeloma (RRMM) patients who had received at least four prior lines of therapy and whose disease was triple-class refractory, indicating progression on the last therapy. Blenrep was subject to a conditional marketing authorisation at that time. The claim at issue, which appeared on the Blenrep homepage, stated:
“BLENREP had a generally well tolerated and manageable safety profile”
The Panel noted the webpage on which the claim at issue appeared was the homepage of the Blenrep section of the GSKpro website, GSK’s promotional website for UK health professionals. The Panel considered the layout and the overall impression created by the landing webpage.
The Panel noted that the homepage included a prominent, bold title, “When multiple myeloma returns, think BCMA, think BLENREP”, followed by statements that Blenrep:
1. was only available via the private market in Great Britain,
2. had a conditional marketing authorisation, and
3. was the first and only licensed B-cell maturation antigen (BCMA) targeted antibody drug conjugate treatment for patients with triple-class refractory multiple myeloma in 5L+.
Below this was a smaller heading, “Why do we need treatment options in multiple myeloma?” which included reasons outlining the need for treatment options, a link to a Blenrep mechanism of action video and Blenrep’s indication. This was followed by bold text which included a brief description of the DREAMM-2 clinical trial and link to access it.
The three green boxes, as referred to by the complainant, appeared below the above-mentioned text and included the titles “BLENREP efficacy”, “BLENREP safety” and “BLENREP dosing and administration” in each box.
The claim at issue, referenced to the Blenrep summary of product characteristics (SPC), was inside the “BLENREP safety” box and included a link to “VIEW SAFETY DATA” in red font.
Further down the homepage, under the title “Why BLENREP?”, were three paragraphs. The second paragraph had the bold heading: “BLENREP has a generally well tolerate [sic] and manageable safety profile”. This statement was referenced to the Blenrep SPC. There were two bullet points under this heading, which stated:
· “Side effects were generally manageable through dose delays and modifications in some patients, with no requirement for steroids as premedication
· In line with the SmPC, some patients may need to discontinue treatment for severe adverse events. 12% of patients (n=11/95) discontinued BLENREP due to adverse events.”
This was followed by a link in bold, red font, titled, “EXPLORE BLENREP SAFETY HERE”.
The Panel noted that the linked safety webpage included three sections:
1. “DREAMM-2 safety summary”. This section included, amongst other things, a table of adverse events, stating the incidence of these events at varying grades of severity and some information regarding discontinuation followed by a second table with data relating to incidence and resolution of eye-related side effects.
2. “Managing eye-related side effects”. This section focussed on managing eye-related side effects through dose delays, modifications or discontinuation with an infographic on how to manage Grade 1-4 side effects.
3. “Blenrep and quality of life (QoL)”. This section included the prominent claim “No change in QoL vs baseline” and illustrated no change in overall patient-reported Global Health Status/QoL, physical functioning or role functioning versus baseline.
The Panel noted the complainant’s overarching allegation that the claim was inaccurate and misleading due to the need to discontinue Blenrep following certain side effects. The complainant referred to infusion related reactions (IRRs) and eye-related side effects.
Infusion related reactions (IRRs)
Section 4.2 of the Blenrep SPC, posology and method of administration, included a table (Table 2) that set out dose modifications for thrombocytopenia and IRRs at varying grades of severity. For moderate to severe IRRs, the recommendation was to provide supportive treatment and once symptoms resolved, resume at a lower infusion rate reduced by at least 50%; permanent discontinuation of treatment and appropriate emergency care was recommended in Grade 3 or 4 (severe) infusion-related reactions in the event of anaphylaxis or a life-threatening infusion reaction.
Similarly, Section 4.4, special warnings and precautions for use, stated to reduce the infusion rate or stop the infusion depending on the severity of symptoms for Grade 2 or higher IRRs and to administer premedication for subsequent infusions (see Table 2). Notably, it included that most reported IRRs were Grade 1 or 2 and resolved within the same day.
Section 4.8 stated that IRRs occurred in 21% of patients, with 90% of these during the first infusion. The majority were Grade 1 (6%) or Grade 2 (12%), with 3% Grade 3. Serious IRRs were reported in 4% of patients, with symptoms such as pyrexia and lethargy. One patient (1%) discontinued treatment due to Grade 3 IRRs. No Grade 4 or 5 IRRs were reported.
The Panel took account of GSK’s submission that published data for daratumumab (the UK’s most commonly prescribed monoclonal antibody for multiple myeloma) reported at least double the IRR rates at Grades 1-3 of severity, requiring pre-medication with antihistamines, antipyretics, and corticosteroids to reduce the risk of IRRs prior to treatment. In contrast, Blenrep's lower incidence and severity of IRRs meant that its SPC did not require pre-medication before the first dose.
According to the DREAMM-2 clinical trial, the majority of IRRs were mild to moderate; 18% of Blenrep treated patients experienced mild to moderate IRRs and 3% experienced severe IRRs. There were no life-threatening or fatal IRRs reported. The Panel noted GSK’s submission that stopping or reducing the rate of infusion in cases of IRRs is normal clinical practice for all infused treatment. Although discontinuation of Blenrep may be clinically appropriate in cases of serious IRRs, the overall incidence and severity of IRRs was low.
In the Panel’s view, the SPC data supported the conclusion that while IRRs were not uncommon, the majority were low-grade and manageable in a clinical setting.
Eye-related side effects
The Panel noted that eye-related side effects were a prominent aspect of Blenrep’s safety profile.
According to Section 4.8 of the SPC, eye disorders occurred in 74% of patients from the safety population in Study 205678 and the most common were keratopathy (71%), blurred vision (25%) and dry eyes (15%). 18% of subjects reported decreased visual acuity in the better eye and 1% experienced severe vision loss. Corneal findings led to dose delays in 47%, dose reductions in 27%, and permanent discontinuation in 3% of patients.
Section 4.2 of the SPC provided detailed guidance for dose modifications in response to varying severity of corneal events, including withholding treatment or discontinuation.
Table 1 of Section 4.2 of the SPC (Posology and method of administration), set out a list of mild, moderate and severe corneal adverse reactions, and recommended dose modifications for each, which included continuing treatment, withholding treatment, resuming treatment at a lower dose or discontinuation. Discontinuation was recommended for worsening symptoms that were unresponsive to appropriate management in severe corneal examination findings (severe superficial keratopathy or corneal epithelial defect) or change in BCVA (best corrected visual acuity) with a decline from baseline of more than 3 lines on Snellen Visual Acuity.
The Panel noted GSK’s submission that it was not feasible to directly compare different products’ eye-related discontinuation rates because, in the RRMM treatment pathway, eye-related side effects were specific to Blenrep.
The safety claim: “BLENREP had a generally well tolerated and manageable safety profile”
While the Panel noted there was no head-to-head data available, it took account of GSK’s submission that discontinuation rates due to any adverse event for Blenrep in the DREAMM-2 trial (8% and 10%) were lower than most of those reported in comparable trials of other 5L+ RRMM medicines, including:
· panobinostat (30%, 28%, 15%),
· elranatamab (13.8%),
· pomalidomide (4% and 6%), and
· selinexor (18%).
GSK maintained that this supported the claim that Blenrep was “generally well tolerated”. In addition, GSK submitted that the 5% Blenrep discontinuation rate for eye-related side effects cited by the complainant was clearly lower and consistent with the claim at issue.
GSK further submitted in support of Blenrep’s tolerable and manageable safety profile that, unlike other BCMA targeting agents (such as teclistamab), Blenrep did not require inpatient admission for administration and monitoring or ICU adverse event management. GSK referred to the MajesTEC-1 trial, in which infections were reported in 76.4% of patients taking teclistamab, with severe infections occurring in 44.8% of cases. This was compared to the DREAMM-2 trial with an overall infection rate of 45%, and 20% at a severity of Grade 3 or higher in patients taking Blenrep.
The Panel accepted GSK’s submission that standard oncology practice involved dose modification, delay, or discontinuation for the management of adverse events, and that these were addressed in the Blenrep SPC.
The Panel considered that it was particularly important that material does not mislead regarding a medicine’s safety profile, especially when associated with adverse reactions that were common and potentially serious.
Clauses 6.1 and 6.2
Clause 6.1 required, among other things, that information, claims and comparisons must be accurate, balanced, fair, objective and unambiguous. They also must not mislead either directly or by implication, by distortion, exaggeration or undue emphasis. Clause 6.1 also required material to be sufficiently complete to enable recipients to form their own opinion of the therapeutic value of the medicine. Clause 6.2 required that any information, claim or comparison must be capable of substantiation.
The Panel considered the issue before it was whether the claim “BLENREP had a generally well tolerated and manageable safety profile”, which appeared twice on the Blenrep homepage, was misleading due to the lack of qualification regarding discontinuation rates due to eye-related side effects. The Panel also had to consider whether the claim was inaccurate as alleged due to the need to discontinue Blenrep following serious eye-related side effects and IRRs. The complainant had not provided why the rate of discontinuation as a result of either adverse event was unacceptable.
The supplementary information to Clause 6.1 required material to be capable of standing alone with regard to the requirements of the Code.
The Panel acknowledged that there was no information on eye-related side effects nor IRRs on the Blenrep homepage. However, the Panel noted that the linked safety page, which was signposted following each occurrence of the claim at issue, detailed information on discontinuation due to eye-related side effects, and the incidence and resolution of these side effects.
The Panel considered that additional detail on IRRs would have been helpful, given it was a very common and potentially serious side effect for which discontinuation could be required. However, the Panel accepted GSK’s submission that the management of IRRs was common in the treatment of RRMM and clinicians would likely be familiar with it. In contrast, eye-related side effects were specific to Blenrep and had been detailed on the linked safety page.
The Panel also observed that the complainant’s allegation in relation to qualification of the claim was limited to discontinuation due to serious eye-related side effects. In the Panel’s view, the claim in question had, on balance, been sufficiently qualified by the linked safety information in relation to eye-related side effects. The Panel further observed that the second appearance of the claim at issue was followed by the statement “in line with the SmPC, some patients may need to discontinue treatment for severe adverse events. 12% of patients (n=11/95) discontinued BLENREP due to adverse events”.
The Panel took account of Blenrep’s black triangle status, that it was subject to a conditional marketing authorisation and that there were established adverse events which could necessitate dose modification or treatment discontinuation. However, the Panel also considered the context in which Blenrep was being promoted; Blenrep was indicated as a fifth-line treatment in RRMM in patients who had received at least four prior therapies and remained triple-class refractory.
The Panel considered the therapeutic area, intended specialised target audience, tolerability data provided by GSK compared with other treatment options, and the cumulative effect of the term ‘generally’. In the Panel’s view, on balance, the complainant had not established that that the claim on the Blenrep homepage was misleading, unqualified or incapable of substantiation. Based on the specific allegation of the claim not being qualified by the eye-related side effects, the Panel therefore ruled no breach of Clauses 6.1 and 6.2.
Clause 5.1 and Clause 2
Based on its rulings of no breaches of the Code above, and in the absence of any other allegations from the complainant, the Panel did not consider that it had been established that GSK had failed to maintain high standards, nor that it had brought discredit upon, or reduced confidence in, the pharmaceutical industry. The Panel ruled no breaches of Clauses 5.1 and Clause 2, accordingly.
Complaint received 13 May 2024
Case completed 9 June 2025
