AUTH/3266/10/19 and AUTH/3279/11/19 - Health Professional v Otsuka UK and Otsuka Europe – Alleged pre-licence promotion

Alleged pre-licence promotion

  • Received
    26 September 2019
  • Case number
    AUTH/3266/10/19 and AUTH/3279/11/19
  • Applicable Code year
    2019
  • Completed
    15 May 2020
  • No breach Clause(s)
  • Breach Clause(s)
  • Sanctions applied
    Undertaking received
  • Additional sanctions
  • Appeal
    No appeal

Case Summary


A health professional complained about two online press releases about ASTX727, a fixed dose combination of oral cedazuridine and decitabine which was being studied for the possible treatment of myelodysplatic syndrome (MDS) including chronic myelomonocytic leukemia (CMML). Astex Pharmaceuticals Inc in the US, a wholly owned subsidiary of Otsuka Pharmaceuticals Co Ltd had issued one of the press releases and the second press release was issued jointly by Astex and Otsuka Pharmaceutical Co Ltd in Japan (OPCJ). The second press release was the subject of another complaint, Cases AUTH/3212/6/19 and AUTH/3262/6/19.

The matter was taken up with Otsuka Pharmaceuticals (UK) Limited and Otsuka Pharmaceuticals Europe Limited as UK based affiliates were responsible for the acts/omissions of overseas affiliates that came within the scope of the Code.

The detailed response from Otsuka UK and Otsuka Europe is given below.

The first press release the complainant drew attention to was headed ‘Astex Pharmaceuticals Announces That Its Novel, Oral Hypomethylating Agent ASTX727 Has Been Granted Orphan Drug Designation for the Treatment of Myelodysplatic Syndrome (Including Chronic Myelomonocytic Leukemia) by the US FDA’. As the press release appeared on a UK website, the complainant considered that it must conform to the ABPI Code.

The complainant alleged that the press release was promotional and that it encouraged patients to request the treatment from their doctors (although not currently available in the UK). The complainant queried whether Astex/Otsuka would undertake to provide the medicine for UK based patients.

The complainant stated that the press release encouraged false hope for patients and queried whether ‘novel’ meant that ASTX727 had additional properties or benefits that no other current treatment had.

The first matter for the Panel to consider was whether the press releases were covered by the ABPI Code. The Panel noted that it appeared that the complainant had accessed the press release via uk.finance.yahoo.com. The Panel noted the submission from Otsuka Europe and Otsuka UK that the first press release was issued by Astex in the US. Otsuka Europe and Otsuka UK did not issue, approve for issue or authorize the press release. There was no mention of use of the medicine in the UK or Europe. The Panel also noted Otsuka Europe and Otsuka UK’s submission that they did not review the press release as it was confirmed that it was not going to be issued in any country outside the US.

The Panel noted that the press release was circulated via third parties in the UK and Ireland as well as the US channel by Astex Pharmaceuticals Inc which was a wholly owned subsidiary of Otsuka Pharmaceuticals Co Ltd. The press release had been widely circulated to UK media organisations many of which were aimed at consumers.

The Panel considered therefore given the circulation to UK outlets , the press release was covered by the UK Code. The Panel noted the involvement of Otsuka Europe and Otsuka UK. However, it was a clearly established principle under the Code that the UK company was responsible for acts and omissions of its overseas affiliates that came within the scope of the Code.

The Panel noted Otsuka Europe and Otsuka UK’s submission that ASTX727 did not have a marketing authorization in any country, the Panel considered therefore that it was not classified as a prescription only medicine. Relevant clauses of the Code regarding relations with the public only applied to prescription only medicines. On this very narrow technical point the Panel ruled no breach of the Code. However, the Panel considered that the press release issued to the public promoted an unlicensed medicine which meant that high standards had not been maintained. A breach of the Code was ruled.

With regard to the use of the word ‘novel’, the Panel noted the companies’ submission that this was justified as it was an oral treatment and included an oral form of decitabine, which was currently only licensed as an IV treatment. Further it was a patented medicine. The Panel considered that the audience would understand novel to mean that the medicine, ASTX727 was new and unusual. The product had been granted orphan status. The Panel noted its comments and rulings above that ASTX727 was not a prescription only medicine. The Panel therefore ruled no breach of that clause with regard to the allegation that in using the word ‘novel’ to describe ASTX727 the press release would raise unfounded hopes of successful treatment. The Panel did not consider that the complainant had established that describing ASTX727 as novel was misleading and no breach of the Code was ruled.

The Panel noted that a breach of Clause 2 was used as a sign of particular censure and was reserved for such use. The Panel considered that the circumstances did not amount to a breach of the Code and ruled accordingly.

The second press release the complainant drew attention to was headed ‘Astex Pharmaceuticals and Otsuka announce results of latest study’. The study in question was the phase 3 ASCERTAIN Study with ASTX727.

The complainant alleged that the press release made outlandish claims, such as the safety and clinical profile of the medicine were similar in early trials but provided no additional data. It was clear from the press release that the medicine was not available in Europe but it encouraged patients to seek it out, given its positive results and the opportunity to participate in clinical trials. More concerning was some of the safety claims. ‘The complainant alleged that the press release did not provide the reader with appropriate context (the data was from pharmacokinetic study).

The complainant would like to see the evidence to support the statement, ‘… the fixed dose combination of cedazuridine with decitabine enables successful oral delivery of decitabine, alleviating the significant burden of five days monthly IV infusions for patients who may continue to benefit from the drug for several months or even years’. The complainant alleged that such claims were marketing claims and had no place in a press release. Such a statement did not do favours for evidence-based medicine.

The Panel noted that although the press release was issued by Astex in the US and Otsuka Japan and Otsuka Europe and Otsuka UK did not issue, approve for issue or authorize the material and there was no mention of use of the medicine in the UK or Europe it was howevera clearly established principle under the Code that the UK company was responsible for acts and omissions of its overseas affiliates that came within the scope of the Code.

The Panel noted that it appeared that the complainant had accessed the press release via cambridgenetwork.co.uk. The Panel noted that the press release was circulated via a third party by Astex Pharmaceuticals Inc which was a wholly owned subsidiary of Otsuka Pharmaceuticals Co Ltd. A list of the third party’s circuits for press releases was provided by Otsuka which included circuits for the UK and Ireland. The Panel noted from emails provided by Otsuka Europe and Otsuka UK that both were aware that the press release was going to be issued in the UK and Ireland. From the detailed list provided in these cases the Panel noted that the press release had been widely circulated to UK media organisations many of which were aimed at consumers.

The Panel noted the companies’ submission that Astex approached Otsuka Europe’s communications team which liaised with Otsuka UK and a review of the press release using Zinc was initiated. The Panel queried why that review was not completed given that emails stated that ‘we have to put joint Astex/Otsuka press releases through [Otuska UK] review if released in the UK’.

The Panel considered that given the circulation to UK outlets , the press release was covered by the UK Code. The Panel noted the involvement of Otsuka Europe and Otsuka UK.

The Panel also noted that Otsuka Europe and Otsuka UK had provided a further copy of their response to Cases AUTH/3212/6/19 and AUTH/3262/10/19 as their response to the allegations in this complaint. The complaints were similar but not the same.

The Panel noted that the press release referred to the safety and clinical activity of ASTX727 being similar to that observed in a previous study. It was stated in the press release that the outcome demonstrated that the fixed dose combination enabled ‘…successful oral delivery of decitabine alleviating the significant burden of five days of monthly IV infusions for patients who might continue to benefit from the drug for several months or even years’. It was further stated that ASTX727 could bring a new treatment option to patients with ‘these deadly diseases’. The press release also stated that ‘ASTX727 is an investigational compound and is not currently approved in any country’.

Given the circumstances the Panel did not consider that the distribution of the press release for an unlicensed medicine in itself meant that that medicine had been promoted. Nor did the Panel consider that the mention of other studies in the clinical programme necessarily promoted the medicine for those indications. It was not unreasonable to give an overview. The Panel considered that some of the language within the press release was promotional as acknowledged by Otsuka Europe and Otsuka UK.

The Panel noted Otsuka’s submission that although decitabine was licensed in the UK, the combination with cedazuridine (ASTX727) was not and that in the UK decitabine IV was licensed for newly diagnosed, de novo, or secondary acute myeloid leukaemia. The Panel also noted that the ASCERTAIN Study was a pharmacokinetic equivalence study and that safety and efficacy were secondary endpoints. The Panel agreed with Otsuka that statements about alleviating the burden of IV infusions, survival benefit, low level of gastrointestinal adverse events and the benefit of oral treatment were misleading and not capable of substantiation. The Panel ruled a breach of the Code as acknowledged by Otsuka UK and Otsuka Europe. There did not appear to be clinical evidence to support the claims for ASTX727 and gastro-intestinal side effects ; it was not clear from the outset that the study was a pharmacokinetic study and safety was a secondary endpoint. Thus, the Panel ruled a breach of the Code.

The Panel noted that ASTX727 was not classified as a prescription only medicine. Relevant clauses of the Code regarding relations with the public only applied to prescription only medicines. On this very narrow technical point the Panel ruled no breach of those clauses. However, the Panel considered that the press release issued to the public promoted an unlicensed medicine which meant that high standards had not been maintained and a breach of the Code was ruled.

The Panel considered that high standards had not been maintained with regard to the information about the study outcomes as ruled in breach of the Code above. The Panel therefore ruled a further breach of the Code.

The Panel noted that a breach of Clause 2 was used as a sign of particular censure and was reserved for such use. The Panel considered that the circumstances did not amount to a breach of the Code and ruled accordingly.