Merck Serono asks EMEA to re-think Erbitux rejection
pharmafile | July 30, 2009 | News story | Research and Development, Sales and Marketing | Cancer, EMEA, Erbitux, Europe, Merck Serono
Merck Serono is to appeal against the European rejection of Erbitux as a lung cancer treatment.
Erbitux has been rejected as a first-line treatment in advanced or metastatic non-small cell lung cancer, Europes Committee for Medicinal Products for Human Use (CHMP) ruling that its benefits did not outweigh its risks.
Data from Merck's FLEX phase III trial shows patients lived on average 11.3 months once treatment had begun, representing an increase of just over a month compared to patients on chemotherapy alone.
The CHMP says this increase in survival time is too short to warrant its approval, but Merck says it is surprised and disappointed at the ruling.
The company says the decision goes against opinion among leading oncologists, and that Erbitux is the first new drug in over a decade to prolong the lives of NSCLC patients including all histologies.
Erbitux has been approved as a treatment for metastatic colorectal cancer since 2003, and is also used against some head and neck cancers, but this is Merck Serono's first application for its use against NSCLC.
Roche's Avastin is the only new targeted therapy already approved as a first line treatment for NSCLC in combination with chemotherapy. It gained its licence in 2006, and is shown to prolong lives of patients with non-squamous NSCLC for two months, and patients with the adenocarcinoma sub-type could gain an extra four months.
Merck Serono have positioned Erbitux as a treatment for patients across all the sub-types of NSCLC, and hopes the European regulator will re-examine the data and change its mind.
Elmar Schnee, head of Merck's pharmaceutical operations, expressed surprise and disappointment at the ruling on Erbitux.
"We never detected that a no-approval could be an option," he said on a conference call with analysts. "I am puzzled how you could come to this decision [with] the data we provided."
Appeal
Wolfgang Wein, executive vice president of oncology at Merck Serono, said Merck had a good basis for an appeal against the decision.
He restated the fact that the drug had shown a statistically significantly improved endpoint compared to typical standard chemotherapy, with manageable side effects.
He added that the FLEX study population was a "very realistic" one – in that patients on the trial were in very poor health and that their disease was very advanced.
Because of this higher levels of toxicity were witnessed than in comparable trials, but Wein maintained that side effects seen were "usual and manageable".
Commenting on the patient population used in the trial he said: "The point is that clinical trials sponsors are encouraged to use a realistic population. But it sometimes does not work out in your favour to do so."
Wein said steps that could be taken to work with the CHMP included post-approval commitment and re-analysing the data.
He said Merck had received a lot of correspondence from doctors and lung cancer experts expressing their surprise at the decision.
Professor Nicholas Thatcher, professor of medical oncology, Christie Hospital NHS Trust, Manchester told Merck:
"As a clinical expert, it is absolutely unclear what the scientific grounds for CHMP rejection were. The benefit for patients has been clearly demonstrated in terms of increased survival. Physicians should have the choice as to whether to use this therapy."
NSCLC
Non small cell lung cancer (NSCLC) remains an area of significant unmet need, although many companies are now researching the use of new targeted agents. NSCLC is the leading cause of death from cancer in Europe, accounting for 20% of all cancer deaths.
Erbitux works by inhibiting a molecular structure called the epidermal growth factor receptor (EGFR), which contributes to the growth of tumour cells.
Many oncologists hope that Erbitux can join Roche's Avastin as another first-line treatment option against the disease.
Academic opinion on Erbitux has been particularly positive. The FLEX trial data was selected as one of the three most important studies at the 2008 American Society of Clinical Oncology (ASCO) meeting in 2008.
The Lancet said Erbitux could be regarded as "a new standard first-line treatment option" for patients with EGFR-expressing advanced non-small cell lung cancer.
The drug is already approved as a first-line treatment for metastatic colorectal cancer and head and neck cancer, but approval in NSCLC would mean a major expansion in its use.
Analysts believe Erbitux could achieve the highest level of sales of the molecular NSCLC therapies in late-stage development: $473m by 2017.
Having registered its appeal, Merck has 60 days to submit a new analysis. The company says it could take until early next year for the company and committee to reach a revised decision.
Erbitux in advanced NSCLC has also reached a stumbling block in the US, where it is marketed by ImClone and BMS.
The companies submitted the drug for approval as a first-line treatment but used data from Merck's version of the monoclonal antibody rather than the US approved version.
The FDA asked the companies to submit data proving the two versions work in similar ways. The companies have withdrawn the drug and say they intend to re-submit for FDA approval at a later date.
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