SPECIAL REPORT #19

Single-arm studies in oncology

In the April issue of MedNous, Bruno Pagliara, Principal at On-Kòs Pharma, is reporting new data about the use of single-arm studies for the development and registration of new oncology drugs.  Single-arm studies involve one treatment group where all patients included receive the same experimental therapy, unlike randomized studies where subjects are assigned to the investigational drug or to a comparator.

In the report Bruno Pagliara shows that in 2018, 21 regulatory oncology approvals (40% of all oncology approvals) where granted by the US FDA, up from 4 (23.5% of all oncology approvals) back in 2013.

Single-arm studies have their limitations such as difficulty to demonstrate the efficacy of the investigational drug in the absence of a comparator, or the limitation of relevant clinical endpoints needed to assess the real benefit. On the other hand, single-arm studies are a way to speed up the development and the registration of a drug with a real potential. Oncology drug developers are increasingly electing this development scheme which for the time being is only accepted by the US FDA and cannot be used alone by the European or the Japanese regulatory authorities for registration.

Single-arm studies are being used for new drug approval as well as for new indication.  As stated above, 40% of all US oncology approvals in 2018 involved single-arm studies. Eight of the 15 new approvals were based on such studies, whereas 13 out the 37 new indication used them. Unlike the new approvals most of the new indications involved accelerated approvals with a requirement to provide follow-up data. These accelerated approvals included a substantial number of combination therapies.

Through a highly illustrating table, with efficacy data supporting 43 US drug approvals with single arm studies, the report shows that 21 of them had less than 100 patients in their study, one of them with only 13 subjects.

Although European and Japanese authorities are not keen to accept single-arm studies for approval it is interesting to have a closer look at the analysis made by Bruno Pagliara in relation to the fate of these drugs outside of the US. Four out of the 16 US approvals using single-arm studies were approved in Europe, while in Japan only three have been granted marketing authorization. For the new indications the pattern is similar: six out of the 27 new indications approved in the US have been approved in Europe whereas in Japan the number is only two.

In his conclusion Bruno Pagliara writes: “The argument for using single-arm studies to approve new cancer drugs is straightforward. It is to make innovative new medicines available without unnecessary delay. It is clear that the FDA is leading the world in this endeavour”.

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