Who has it right on drugs regulation - the FDA or the EMA?
This article was originally published in Scrip
December is closing the year with a harrowing bang for the pharmaceutical industry, as it seemingly always does. But this bang was loud and explosive, exposing anew a divergence in regulatory decision-making between the FDA and the EMA.
Three decisions coming in rapid-fire in December are cause for some significant year-end reflection. The FDA decided to remove the breast cancer indication from Avastin, Roche’s blockbuster biotech cancer drug, as it determined that the efficacy could not justify potential risks; the EMA maintained Avastin’s breast cancer indication but would restrict its use with certain standard chemotherapies.
Then, the EMA gave a positive opinion on approval for InterMune’s Esbriet (pirfenidone) to treat idiopathic pulmonary fibrosis – a fatal lung disease with few or no treatment options. But the FDA has balked at approving the drug, and InterMune says it will form a US regulatory strategy early next year – despite its disbelief that both agencies asked similar questions and came to radically different conclusions.
And last but not least, AstraZeneca was stunned to find in its Christmas stocking an FDA complete response letter effectively delaying approval for Brilinta, its new anti-platelet blood-thinning drug. Brilinta, sold in Europe as Brilique, received its EMA positive opinion in September and EU approval in December.
If you talk to industry, investors and other stakeholders, they fear that the FDA has completely lost the plot. The FDA is putting its own process and reputation ahead of patients by letting the risk balance pendulum swing far too wide, they say.
Indeed there is worry boiling up from the wellspring of pharmaceutical research – venture and other early-stage investors – that regulatory uncertainty with the FDA is choking off risk appetite to fund new research, new companies, and new treatments.
What about the EMA? Are they enlightened regulators? Or just pushovers compared with the hard nuts at the FDA? Maybe it's simply a matter of cultural differences.
Each agency has had a drive to improve safety, whether in pre-approval testing or post-approval benefit-risk assessments. Each agency has put out maps to try to improve the drug development process for the betterment of public health. There has been collaboration, harmonisation, and communication. And yet, we still end up with significantly different answers in the end.
It could be instructive to recognise that the EMA stands in front of some other significantly powerful gatekeepers to the return on investment of new treatments/research and to the overall benefit/risk profile. Beyond the EMA’s decisions lies the uncertainty of cost-effectiveness/HTA evaluations in EU countries. NICE in the UK, for example, has just turned down Avastin with chemotherapy for metastatic bowel cancer, and given a preliminary “no” to Tyverb and Herceptin in breast cancer.
Bodies like NICE can absorb blows on decisions, leaving the EMA more cover to do its regulatory business. The FDA is the only whipping horse in the US – at least these days.
I am reminded of those crazy three days in February 2005 at the FDA advisory committee meeting on COX-2 inhibitors, particularly Vioxx. People were crammed into every room, hallway, corner or lobby of the dreary isolated hotel where it was held. Many at the time compared the scene only with the crowds and energy at the charged meetings in the previous decades by advocates for new HIV therapies. The former brought safety to the fore of US regulatory culture, the latter brought accelerated new drugs.
The FDA has successfully shown its teeth. It’s a tough regulator. The Avastin decision is likely a shot across the bow that accelerated conditional approval means just that – accelerated CONDITIONAL approval even for wonder drugs like Avastin. Fair enough. Nevertheless, the EMA keeps shining a harsh contrasting light on its decisions and posture.
In a global industry with rising countries that could be global healthcare powerhouses, the EMA feels competitive in a changing world. The FDA feels like it’s still fighting yesterday’s battles. Tomorrow’s decisions are the key – and the search for balance goes on. If regulators ever hit it, I hope we all can laud it when it comes – for the good of everyone’s health.