Mirati clears first clinical hurdle in KRAS race against Amgen

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Shares in Mirati climbed 14% in after-hours trading. (La Jolla Institute)

Mirati Therapeutics’ KRAS G12C inhibitor MRTX849 has cleared its first clinical hurdle. The startup posted initial clinical data that suggest MRTX849 can hold its own against Amgen’s rival cancer drug, although the small numbers of patients treated to date make it impossible to draw firm conclusions.

As of the cutoff, 12 patients treated with MRTX849 had undergone a radiographic scan to assess the impact of the drug. Of the six non-small cell lung cancer (NSCLC) patients, three had partial responses, resulting in a response rate in line with that achieved by Amgen in the indication. One of the four colorectal cancer (CRC) patients assessed to date had a partial response.

“Overall we see no change to the [Amgen] thesis and consensus expects competition and data in our view say the competitor is not clearly better or worse in any way. So the two will move forward and the expected competition will continue but both look active,” analysts at Jefferies wrote in a note to investors.

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Mirati’s numbers get better when the analysis is limited to its preferred dose, although that further shrinks the patient population and by extension increases the risk the data will paint an erroneous picture of the efficacy of MRTX849. 

In the high-dose subgroup, three of the five NSCLC patients and one of the two CRC subjects had responses. At 60%, the NSCLC response rate is slightly above that seen in Amgen’s trial, although the history of that study shows it is unwise to read too much into results in small numbers of patients. Amgen had a 100% response rate in NSCLC after treating three patients, but the figure has slipped as the study population has expanded. 

Those events show the need to interpret Mirati’s CRC data cautiously, but, as it stands, that is one area in which it may have an edge over Amgen. Across 29 CRC patients, Amgen has seen one response, resulting in a response rate of 3%. Mirati’s CRC response rate stands at 25% or 50%, depending on whether all subjects or just those who received the high dose are included. But it is possible the one CRC response seen in Mirati’s trial is an outlier, and the rate will fall steeply as the trial grows. 

Analysts at Jefferies identified the apparent deepening of the responses seen in two patients as another potential positive for Mirati. Tumor shrinkage in those patients went from 37% to 47% and 33% to 43%, suggesting durable, improving responses to MRTX849 are possible. 

On the flip side, Mirati’s best data come from a twice-daily regimen, compared to Amgen’s once-daily dosing, and the startup has encountered one case of a grade 3/4 increase in pancreatic enzymes. The only other dose-limiting toxicity stemmed from intolerance to the burden of a 12-capsule regimen, which isn’t the schedule Mirati selected for the dose expansion phase. 

Shares in Mirati climbed 14% in after-hours trading, adding to a valuation that had already topped $3 billion on excitement about the potential of finally drugging KRAS. Amgen finished the day up by 1%.

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