AUTH/2351/8/10 - Lilly v Roche
Case Number: AUTH/2351/8/10
Case Ref: Lilly v Roche
Description: Promotion of Tarceva
Breach: No breach
Appeal: Appeal by respondent
Review: Published in the February 2011 Review
Complaint Received: 19 August 2010
Complaint Completed: 10 November 2010
Lilly complained about the promotion of Tarceva (erlotinib) by Roche. The items at issue were a leavepiece, an advertisement in Oncology Times and a sponsored feature in Oncology News. Tarceva was indicated as monotherapy for maintenance treatment in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with stable disease after 4 cycles of standard platinumbased first-line chemotherapy. It was also indicated for treatment in locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. Lilly supplied Alimta (pemetrexed).
Lilly stated that the items at issue all claimed that Tarceva was licensed for use as ‘first-line maintenance’ therapy in advanced NCSLC. Lilly had further complained to Roche that the front of the leavepiece stated that Tarceva was ‘now licensed for first-line maintenance in patients with stable disease’, without clarifying that the specific indication was for the treatment of advanced NSCLC.
The treatment algorithm for patients with advanced lung cancer was complex. Lilly explained that firstline and maintenance treatment of locally advanced or metastatic NSCLC were two distinct and specific indications; first-line being the indication of induction treatment, usually with platinum-based combination chemotherapy, followed by maintenance treatment which was the initiation of treatment in patients whose disease had not progressed immediately following first-line therapy. The majority of the patients were treated with firstline treatment options and observed until disease progression became evident, at which stage licensed second-line treatment options could be considered. Until recently, no medicine was specifically licensed for the maintenance setting. The first product licences for maintenance treatment were granted for Alimta in 2009 and Tarceva in 2010. Alimta was indicated as monotherapy for the maintenance treatment of locally advanced or metastatic NSCLC other than predominantly squamous cell histology in patients whose disease had not progressed immediately following platinum-based chemotherapy. First-line treatment should be a platinum doublet with gemcitabine, paclitaxel or docetaxel.
Currently, licensed medicines were available for first-line, second-line or maintenance. Patients whose disease had progressed after first-line or maintenance therapy were eligible for second-line treatment. Roche had argued that ‘first-line maintenance’ was used to distinguish from secondline maintenance. However, a licence for second-linemaintenance per se did not exist.
Given the multiple treatment variations, possible treatment algorithms and the inherent potential for confusion, the Tarceva and Alimta indications, as defined by the European regulators, were very specifically worded. Lilly alleged that the claim ‘first-line maintenance’ was ambiguous, misleading and not consistent with the Tarceva SPC.
In the absence of a clear statement on the front of the leavepiece of the intended therapeutic use, Lilly believed that physicians might believe that Tarceva could be used in unlicensed NCSLC settings (eg stage IIIA patients) or indeed in any other cancer. Lilly alleged that such omission amounted to misleading promotion outside the licensed indication in breach of the Code.
The Director noted that the leavepiece had been withdrawn by Roche during inter-company dialogue. Inter-company dialogue had been partially successful. The new leavepiece however, still included the claims cited by Lilly above and so these were referred to the Panel.
The detailed response from Roche is given below.
The Panel noted that the Alimta SPC referred to its use as first-line treatment, maintenance treatment following first-line chemotherapy and second-line treatment in NSCLC. Tarceva was indicated for maintenance treatment following first-line chemotherapy and for treatment following the failure of at least one prior chemotherapy regimen. The Panel noted that the Tarceva leavepiece included the claims ‘Now licensed for first-line maintenance in patients with stable disease’ and ‘Tarceva now approved as first-line maintenance’. There were other references to ‘first-line maintenance’. ‘First-line maintenance’ was not used in the Tarceva SPC. This appeared to be a term used by Roche to describe Tarceva’s use in stable disease following platinum doublet chemotherapy. In the Panel’s view, the use of the term ‘first-line maintenance’ therapy was ambiguous; it implied that there might be a product for second-line maintenance or that Tarceva should be used for maintenance therapy before any other therapies also licensed for maintenance. Neither was so. The Panel noted Roche’s submission that ‘first-line maintenance’ was cited in the medical literature. Nonetheless the promotion of a medicine must not be inconsistent with the particulars listed in its SPC. The Tarceva SPC did not refer to ‘first-line maintenance’. In that regard the Panel considered that the use of ‘first-line maintenance’ was misleading and inconsistent with the Tarceva SPC.The product had not been licensed or approved as ‘first-line maintenance’ as stated. Reference to the product licence in this regard appeared to validate Roche’s description. Breaches of the Code were ruled. This ruling was appealed by Roche.
The Panel considered that the absence of the licensed therapeutic use on the front page of the new leavepiece was not in itself misleading. The front of the leavepiece did not mention any type or stage of cancer. In this regard it was not inconsistent with the SPC and no breach of the Code was ruled.
The Panel noted that the advertisement was headed ‘A lifeline after first-line chemotherapy in advanced NSCLC’ followed by a photograph of the palm of a hand beneath which was the claim ‘Now licensed for first-line maintenance in patients with stable disease*’. The explanation for the asterisk appeared in smaller typesize immediately beneath the claim ‘Tarceva is indicated as monotherapy for maintenance treatment in patients with locally advanced or metastatic NSCLC with stable disease after 4 cycles of platinum based first-line chemotherapy’. The Panel noted that it was a principle under the Code that claims should be capable of standing alone without relying on footnotes to provide further explanation.
The Panel considered that the claim in the advertisement ‘Now licensed for first-line maintenance in patients with stable disease’ was in breach of the Code for similar reasons to the leavepiece. This ruling was appealed by Roche.
The Panel noted that each page of the four page article ‘First-line maintenance (1LM) treatment: a new strategy to treat advanced NSCLC’ was headed, in a small font size, ‘Sponsored Feature’. The author was a consultant medical oncologist. At the foot of the first page was a statement that the article was commissioned by Roche Products Ltd, that medical writing support was provided by Darwin Healthcare Communications, paid for by Roche and that the views expressed were those of the author. At the foot of pages 2-4 of the article was the highlighted statement ‘This article is supported by Roche Products Ltd’.
The Panel noted that Roche had not commented on whether or not the sponsored feature was promotional material. The approval certificate stated that the signatories considered it was not promotional and was in accordance with, inter alia, the Code.
The Panel noted that whether a company was responsible for sponsored material depended on a number of factors including whether the material was initiated by a third party, although that in itself did not automatically absolve the company from responsibility under the Code for its content. It had previously been decided in relation to material aimed at health professionals that the content would be subject to the Code if it was promotionalin nature or if the company had used the material for a promotional purpose. Even if neither of these applied, the company would be liable it if had been able to influence the content of the material in a manner favourable to its own interests. It was possible for a company to sponsor material which mentioned its own products and not be liable under the Code for its content, but only if it had been a strictly arm’s length arrangement with no input by the company and no use by the company of the material for promotional purposes.
The Panel noted that the ZINC job summary indicated that Roche had been asked to sponsor a topical article in the Oncology News and that it approached the author and asked him to write an article about first-line maintenance. It was stated that the author retained full editorial control. The objective was to inform readers of the rational and clinical data behind first-line maintenance treatment in NSCLC. In the ‘Notes’ section it was stated that there were plans to get reprints of the article for the HSSs to provide to customers.
The Panel thus considered that there was no arms length arrangements between Roche and the other parties. Roche was inextricably linked to the content of the article. Although the author had retained editorial control, he had been chosen by Roche and the company had defined the scope of the article. The article referred to erlotinib and bevacizumab (Roche’s product Avastin). In the Panel’s view, Roche’s failure to recognise that the article constituted promotional material showed a lack of understanding of the requirements of the Code.
The Panel referred to its comments above in relation to the leavepiece and noted that the article stated that erlotinib could be used for ‘first-line maintenance’ treatment when such an indication was not referred to in the SPC. A breach of the Code was ruled. This ruling was appealed by Roche. The Appeal Board noted that the Code required that a medicine must be promoted in accordance with the terms of its marketing authorization and that promotion must not be inconsistent with the particulars listed in the medicine’s SPC. The Appeal Board further noted that the Code did not require claims to use identical wording to that found in the SPC. In the Appeal Board’s view one of the effects of the Code was to protect patient safety and to stop a patient receiving a medicine when it was inappropriate for them to do so.
The Appeal Board noted that Tarveva materials were targeted at physicians experienced in the use of anti-cancer therapies. In the Appeal Board’s view, experienced oncologists would not be misled as to Tarceva’s position in the management of NSCLC. The Appeal Board did not consider that, to an oncologist, ‘first-line maintenance’ might imply ‘first-line treatment’ or that ‘first-line’ in this context implied the preferred choice. The materials at issue all referred to the use of Tarceva after first-line chemotherapy.
The Appeal Board did not consider that claims in the leavepiece regarding ‘first-line maintenance’ were either misleading or inconsistent with the particulars listed in the Tarceva SPC as alleged. In the Appeal Board’s view, having read the leavepiece, experienced oncologists would be in no doubt which patients should receive Tarceva. The Appeal Board ruled no breach of the Code. The Appeal Board considered its comments and rulings similarly applied to the advertisement and the sponsored feature. The appeal on all points was thus successful.