AstraZeneca PLC (AZN) is attracting attention this week on the back of news that the company has scored a priority review from the FDA for an asset that it is developing in collaboration with big pharma peer, Merck & Co., Inc. (MRK). The asset in question is called Lynparza and the two companies are trying to get it approved in the US as a potential therapy for patients with germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer who have been previously treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic settings.
It’s a big market and one that AstraZeneca will find out whether it can target with this asset by the first quarter of next year, as afforded to the company by a priority review designation.
However, markets are overlooking a second major development today, one rooted in an asset that is currently under investigation a little farther down AstraZeneca’s pipeline, but one that could potentially outweigh Lynparza in terms of impact on topline revenues for the company long-term if it matures through to successful commercialization.
Here is what is important and what to look for next from this program.
The drug in question is called savolitinib and AstraZeneca is investigating it as a potential treatment for patients with non-small cell lung cancer (NSCLC). Many reading will probably already be aware that AstraZeneca has a couple of blockbuster NSCLC assets in its portfolio already, so that it is trying to bring another want to market might seem odd at a glance.
In reality, however, it is anything but.
There is a specific type of lung cancer called EGFR-mutant, MET-amplified NSCLC and patients with this type have proven to respond relatively poorly to the currently available standard of care treatments. Up until recently, physicians thought the EGFR-mutant element of the cancer was the problem and so companies have spent time trying to combine certain drugs that serve to inhibit the EGFR-mutant element and, by proxy, potentially improve efficacy of the primary component of the treatment.
They haven’t been successful, however, and this has pushed AstraZeneca to go after the MET-amplified element as part of an alternative treatment route. Savolitinib is an inhibitor of MET, so the idea is that by combining savolitinib with one of two current standard of care treatments in this space, Iressa or Tagrisso, which are both marketed by AstraZeneca, treatment efficacy can be enhanced. From a mechanism of action perspective, the savolitinib inhibits the MET, which in turn, stops the amplified MET that came about as a symptom of the specific cancer type from inhibiting the Iressa or Tagrisso active compounds, each of which are designed to stop proliferation in NSCLC cells.
When the company first kicked off this program, markets thought it was a bit of a stretch. However, as per some news that just hit press, it now looks as though AstraZeneca has, initially at least, been validated in its efforts.
The company just reported data from two phase Ib/II proof-of-concept trials conducted in this target population (EGFR-mutant, MET-amplified NSCLC) – one investigating the impact of adding savolitinib to Iressa and the other doing the same in Tagrisso.
In the latter, the Tigresso trial, the company compared a combination with a monotherapy of savolitinib and recorded partial responses of 20% for the combination and 40% for the monotherapy respectively.
For the Iressa trial, the company just assessed the combination treatment and was able to show that 11 out of 44 patients recorded partial responses, with the remaining patients up for grabs and potentially combining to translate to a total partial response of up to 34%.
These numbers may seem low, but these are patients that have an advanced form of a very deadly cancer and the fact that even 1 out of 5 is responding is a strong indication of potential efficacy in this population.
So what’s next?
Near term, the completion of the Iressa trial and the subsequent bottom line partial response rate could be a major catalyst for this program.