Mirati's KRAS drug beats estimates in Q1, but Keytruda combo plan remains unclear

Just as Amgen’s KRAS contender Lumakras suffered a sequential sales decline, Mirati Therapeutics’ rival drug Krazati has surprised analysts in its first full quarter on the market. But investors remain more interested in Mirati’s plan for newly diagnosed lung cancer patients.

After an FDA approval in KRAS-mutated non-small cell lung cancer (NSCLC) in December, Krazati generated $6.3 million in the first three months of 2023, coming in ahead of Wall Street’s expectation of $3.4 million.

Krazati delivered that beat just as Lumakras’ sales in the U.S. slumped by $14 million, or 23% lower than its haul in the fourth quarter of 2022.

In a sign of early interest in the therapy, Krazati has captured a third of new patient starts, Mirati’s chief commercial officer Ben Hickey told investors during a call Tuesday. Among the top 50 doctors that Mirati is targeting with its awareness efforts, 80% have prescribed Krazati, he added.

The majority of patients who received the medicine were new to a KRAS inhibitor, but some switched from Lumakras, Hickey said. The switches often happened when doctors had seen liver toxicity issues with Lumakras or if the patient developed brain metastasis, he said.

In a win for Krazati against its competitor, the National Comprehensive Cancer Network recently added the Mirati drug to its guidelines for patients with brain metastasis, a status that Lumakras doesn’t have.  

Although Krazati is giving biotechnology giant Amgen a run for its money, the fact that Lumakras should decline so early in its launch—even as Krazati has yet to meaningfully tick up—is a concerning sign for both drugs, at least in their current second-line indications.

That’s why industry watchers have been focusing on KRAS combinations with PD-1 inhibitors in newly diagnosed patients. In its initial combo data released last year, Lumakras disappointed when added to Merck's Keytruda, with experts flagging a notable liver safety problem. Krazati didn’t have that side effect concern in its own Keytruda combo study, but the pairing’s efficacy was less than a decisive win compared with Keytruda alone.

Originally in its combo efforts, Mirati said it was planning two phase 3 trials pairing Krazati with Keytruda in patients with different PD-L1 expression levels. 

But Mirati later launched another phase 2 trial of a four-drug combination of Krazati, Keytruda and two chemotherapies. There, Krazati is being added to the regimen from the landmark KEYNOTE-189 trial, which showed the Keytruda-chemo combo cut the risk of death by half in front-line NSCLC.

“Given an efficacy profile that some investors viewed as modest for the [Krazati + Keytruda] doublet, the addition of chemo may increase the efficacy,” SVB Securities analysts said in a Wednesday note. But the team also noted that KEYNOTE-189 already set a high bar for efficacy.

Mirati will have updated data from the doublet’s trial later this year to include response duration and tumor progression analyses by PD-L1 scores, Chief Medical Officer Alan Sandler, M.D., said on the call. As for the new chemo combo study, the main goal is to evaluate safety, he said.

Once Mirati has the updated data from the doublet and some initial results from the quadruplet later this year, it will be able to decide on the first-line approach in each patient population, Sandler said.

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In addition to lung cancer, Mirati plans to seek accelerated approval for a cocktail of Krazati and Eli Lilly’s Erbitux in third-line colorectal cancer in the fourth quarter. The company is conducting a phase 3 study in the second-line setting as the confirmatory trial, with those data expected in 2024.

By comparison, Amgen is running a phase 3 for Lumakras in combination with its own Vectibix in third-line colorectal cancer, with the readout planned in the second half of 2024.

Outside of those cancers, Mirati last month unveiled promising data from the phase 2 KRYSTAL-1 study. The trial showed Krazati triggered clinical activity in a group of patients with various KRAS G12C-mutated solid tumors.

Mirati is talking with the FDA about that readout, Sandler said Wednesday. The company is gearing up for a tumor-agnostic approach but has a backup plan to seek individual indications in pancreatic cancer and cholangiocarcinoma, where Krazati was associated with better tumor responses, he added.