Press Release: Workshop on chordoma discusses challenges of drug development for rare cancers

Date: 04 Jun 2015: EMA, ESMO and RCE joint workshop on chordoma as a model for very rare cancers

4 June 2015. To date, there is no drug approved for medical therapy of chordoma (1) patients. Supporting research for chordoma (a very rare cancer arising from the skull base or the spine and affecting only one person in a million per year) was the focus of talks that took place on 30 April 2015 at the European Medicines Agency (EMA) in London. The workshop was attended by patients, oncologists, pathologists, regulators, statisticians and industry representatives.

Because of their rarity, it is difficult to organise large randomised clinical trials for rare cancers and chordoma in particular. The aim of the meeting was to identify possible methodological solutions that could work for this and other very rare cancers. Participants discussed scientific and regulatory evidence requirements for drug approval in rare diseases and other important hurdles faced by researchers today.

“Today, in most cases, tumours are surgically removed, followed by radiation therapy, but the proximity of chordomas to the brain stem and nerves makes surgery risky and limits the dose of radiation that can be delivered safely. There is an urgent need for alternative treatment,” said Dr Paolo G. Casali, co-chair of the meeting Board member of the European Society for Medical Oncology. Rare Cancers Europe (RCE) advocates for innovative approaches and different methodologies to be applied for rare cancers (2) while ensuring patient safety.

In a common disease scenario, drugs are developed and presented to regulators for approval by the pharmaceutical industry. However, in rare cancers, the market is by nature limited and companies do not find the financial incentives needed to invest in them. In chordomas, innovation is currently driven mainly by patients themselves, supported by academia. Researchers have been exploring drugs approved for other diseases. These studies have shown some activity but the evidence gathered has not been judged sufficient in the past, because of the lack of control groups to compare results with.

During the workshop, discussions focused on the kind of evidence that would be acceptable to scientists and regulators alike. Researchers wanted to know what kind of evidence EMA would require for approval of innovative drugs for chordoma.

Dr Francesco Pignatti, Head of Oncology, Haematology and Diagnostics at EMA, said that the agency’s mission was to measure benefits versus risks. “There is no such thing as a ‘regulator trial’. The EMA will examine all evidence (both quantitative and qualitative),” explained Pignatti. “We do not only look at the ‘p’ value, we are open to other endpoints and understand that in rare diseases randomised clinical trials are not always possible.” Pignatti said the pharmaceutical industry should not “over interpret” regulation.

Industry representatives attending the workshop also requested clearer guidelines from the EMA in order to facilitate the registration of innovative drugs for rare indications. “Currently the process is long and costly, which discourages the pharmaceutical industry from embarking on licensing of drugs for rare cancers. We have nevertheless supported research into chordoma by providing scientists with drugs for research on a voluntary basis, but we need to move forward from a voluntary cultural approach to a more systematic approach for registering new drugs for rare cancers,” said Dr Daniele Alberti, Head of Medical Affairs, from Novartis Oncology, Region Europe.

“Randomisation is not meaningful or ethical in life threatening situations, such as chordomas,” said Dr. Bettina Ryll, from the Melanoma Patient Network Europe (MPNE), Chair of the ESMO Patient Advocates Working Group (PAWG). “When there is no alternative and no perspective, patients don’t want to be randomised to a treatment known to be inferior, they see clinical trials as access to innovative drugs. Patients’ different attitudes to risk should be respected and we need trial designs combining early access with systematic learning, for everyone’s benefit. Healthy persons’ fear of risk cannot mean that someone in a desperate situation is denied access to experimental drugs,” stated Dr Ryll who lost her husband to melanoma.

Dr Casali stressed that society should not discriminate against diseases which only affect minorities. He urged stakeholders to draw conclusions from this workshop and to organise further meetings on other rare cancers.

As Josh Sommer, patient and founder of the Chordoma Foundation put it: “Policy advances slowly, disease doesn’t.”

In concluding, participants highlighted the importance of multi-stakeholder discussions to ensure better understanding of different priorities and requirements. Regulators expressed their willingness to provide further guidance on clinical trials in rare cancers, in answer to the request from patients, industry and academia. “The EMA is committed to continuing discussions with rare cancer stakeholders and to provide advice during the drug development process in order to support vital innovation in the field of rare cancers,” concluded Dr Pignatti.


1 About chordoma:

2 Rare Cancers Europe methodological recommendations for clinical studies in rare cancers: a European consensus position paper. Ann Oncol (2014) doi: 10.1093/annonc/mdu459

3 EMA-ESMO workshop on the methodology of clinical studies on rare cancers. October 2014.


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