The ability to diagnose cancers with specific genetic alterations offers new hope for developing targeted treatment options for patients. For example, an estimated 22% of all solid-tumor cancers harbor a mutation in the KRAS gene. While there are multiple types of KRAS mutations, Amgen (AMGN) made history in 2021 by earning the first approval for this high-value target that was once considered "undruggable."
Others aren't far behind, although the distance to the leader seems to shrink or grow with each press release from the competitive landscape.
Lead competitor Mirati Therapeutics (MRTX) has encountered delays and executive churn, but has nonetheless managed to deliver data on par with Amgen's drug Lumakras (sotorasib). The latest data for the experimental challenger, known by its chemical name adagrasib, sent shares of Mirati Therapeutics soaring 36% and once again muddied the competitive landscape in KRAS.
A Promising Development for Patients
Both Amgen and Mirati Therapeutics chose to first test their experimental treatments in non-small cell lung cancer (NSCLC). It accounts for nearly 236,000 new cancer cases in the United States each year, including an estimated 31,000 with the KRAS G12C mutation targeted by Lumakras and adagrasib. That made it easy to identify and enroll patients in clinical trials and represented a large commercial opportunity if studies succeeded.
The complexity of cancer means things aren't so easy, of course. Treatments must be proven to work in very specific circumstances, such as in patients who have never received treatment or in individuals with advanced disease. Considering an estimated 40% of advanced NSCLC cases with a KRAS G12C mutation involve cancer that has spread to the brain, demonstrating safety and efficacy in this patient population would be preferred by regulators and significant for patients.
Mirati Therapeutics reported encouraging data for treating brain metastases in NSCLC patients on June 6. It helps to quickly define some terms before digging into the data.
- Stable disease means tumors aren't shrinking or growing by meaningful amounts.
- A partial response means tumors have decreased in size by at least 30%.
- A complete response means tumors are undetectable.
- A patient is considered to have achieved disease control if they demonstrate stable disease, a partial response, or a complete response.
- A patient is considered to have achieved an objective response if they demonstrate a partial response or a complete response.
Of the 19 evaluable patients at the cutoff date, 16 achieved control of their cancer's brain lesions. That includes 10 individuals with stable disease, three with a partial response, and three with a complete response. That means adagrasib achieved a disease control rate of 84% (16/19) and an objective response rate of 32% (6/19) in NSCLC patients with brain metastases.
The results are impressive and great news for patients. Shares of Mirati Therapeutics jumped 36% after its CEO claimed the results were a first for a KRAS inhibitor. However, that's not quite true. There are some caveats for investors to consider when comparing directly with Amgen's data.
Mirati's Industry-First* Data
The preliminary data reported by Mirati Therapeutics represent the first for a KRAS G12C inhibitor in patients with NSCLC that spread to the brain – in patients who had never received treatment for brain lesions. Once again, Amgen was the first to treat brain lesions in NSCLC patients, but specifically in individuals who had received treatment before.
Lumakras data reported in September 2021 were similarly impressive, including a disease control rate of 88% (14/16) and two complete responses. On the one hand, previously-treated tumors are generally considered more difficult to treat. On the other hand, treating patients earlier generally leads to significantly better outcomes and represents a larger commercial opportunity.
It may be tempting, but investors cannot make comparisons between the two datasets from these companies in NSCLC that has spread to the brain. These are two different patient populations. In reality, the soaring stock price has more to do with the fact Mirati Therapeutics has lost 60% of its market value since the beginning of 2022 -- and that includes the post-data pop.
If those temptations are too great to ignore, then it's fair to say most of the data publicly reported to date suggest Lumakras and adagrasib are essentially equal. The crucial difference is that Amgen's asset appears to drive longer-lasting responses and was first to market, which can lead to significantly larger market share over time. Both assets appear poised for commercial success. Most importantly, they represent much-needed treatment options for tens of thousands of individuals with genetically-defined cancers.
