Medical need and the opportunity to reduce it can vary widely across patient segments within a tumor type. Analyzing those differences can help development teams gain meaningful insights into the range of commercial opportunities across segments.
Roche’s targeted cancer drug Rozlytrek was approved in August 2019 for metastatic non-small-cell lung cancer (NSCLC) patients whose tumors are ROS1-positive. ROS1 rearrangements present in just 1-2% of NSCLC patients, and a little over one third of these patients develop brain metastases. By analyzing the published clinical data in Equinox Group’s modeling framework, we conclude that:
The level of medical need in patients with brain metastases is considerably higher than it is in the writ-large ROS1-positive population, and more importantly
Rozlytrek’s clinical improvement in ROS1-positive patients with brain metastases is substantial, while among the writ-large population the improvement is modest
Comparing the Level of Medical Need in Two Populations
The chart below compares unmet medical need (as measured in Equinox’s model) for the two populations when treated with Xalkori, which was the standard of care for ROS1-positive patients before the approval of Rozlytrek. Patients with brain metastases have 24% higher medical need than the writ-large population. As the chart shows, higher need in the brain metastases population is driven by inferior efficacy and worse mortality outcomes.
Comparing Rozlytrek’s Clinical Improvement over Xalkori in Each Population
When we model Rozlytrek against Xalkori in the writ-large ROS1-positive population, we find little difference in efficacy between the two agents. Rozlytrek’s overall clinical innovation (mostly attributable to safety/tolerability) is only 1.3% in this broader group; historically, drugs with less than 5% clinical innovation are seen as undifferentiated.
However, when we restrict the analysis to patients who have brain metastases, Xalkori is less effective and Rozlytrek achieves an impressive clinical innovation score of 12.8% (drugs with clinical innovation above 10% usually dominate their branded segments). The far greater overall improvement in patients with brain metastases is attributable primarily to over 3 months greater mPFS (we assume mOS changes are proportional, as those data were not mature at publication).
Rozlytrek’s efficacy in cancer that has spread to the brain is an important advantage over Xalkori that is clearly illustrated only when we model the appropriate subset of ROS1-positive NSCLC patients. And while both the writ-large and brain metastases population analyses provide useful information on their own, examining them side-by-side sheds further light on the sources of advantage for the asset in this tumor.