NEW YORK – Amgen reported on Thursday after the markets closed that sales of its KRAS inhibitor Lumakras (sotorasib) continued to ramp up in the second quarter following its launch last year.
In Q2 2022, Amgen recorded overall revenues of $6.59 billion, a 1 percent increase compared to $6.53 billion in Q2 2021. Lumakras, which US regulators approved in May 2021 for advanced non-small cell lung cancer patients harboring KRAS G12C mutations, contributed $77 million in revenues during Q2 2022, compared to $9 million in the year-ago period. Revenues came in below Goldman Sachs' expectation that it would net $80 million in Q2 but exceeded the consensus expectation of $75 million put forth by financial data and software company FactSet. Also among precision oncology drugs, Vectibix (panitumumab), a drug for RAS wild-type colorectal cancer saw a 13 percent decline in revenues to $207 million in Q2 2022, compared to $239 million in Q2 2021.
During a call to discuss the company's financials, Amgen executives highlighted that sales of Lumakras have taken off even though prescribing has lagged due to inadequate testing in the US for the KRAS G12C mutation in the second-line NSCLC setting.
In approving the drug last year, the US Food and Drug Administration also approved two companion diagnostics to identify patients with KRAS G12C mutations: Qiagen's Therascreen KRAS RGQ PCR kit and Guardant Health's Guardant360 CDx. Qiagen's PCR test analyzes tumor tissue, while Guardant's next-generation sequencing test detects mutations in plasma samples.
"We've seen broad adoption in the community setting where the majority of non-small cell lung cancer patients are treated," said Amgen Executive VP Murdo Gordon during the call. "Unfortunately, while 85 percent of patients in the US are tested for their KRAS G12C status, only 50 percent of the time do oncologists have these test results available to support second-line treatment decisions."
Gordon noted that when the patient's KRAS G12C status is known in the second-line setting, 85 percent of those patients receive Lumakras. "Our team is removing barriers to ensure that the oncologist is able to review KRAS G12C status when the patient progresses beyond first-line therapy," Gordon said, adding that there's opportunity to drive further revenue growth in the US by increasing testing rates.
In the US, Lumakras racked up $51 million sales and $26 million in the rest of the world. Gordon said that in markets outside the US, like Germany, Switzerland, and France, where biomarker testing and clinical information systems are more established, "we're seeing very rapid lift and uptake." In other countries that have not implemented testing as widely, such as Spain, Italy, and the UK, uptake of Lumakras is at similar levels as the US.
He added that while this information is specific to Lumakras, other biomarker-informed therapies face the same challenge. "You're going to see a slower uptake in some markets than you will in others because of that testing infrastructure," Gordon said.
In the US, Lumakras has been prescribed to over 3,000 patients by more than 1,900 physicians. The drug is now approved in more than 40 countries, and Amgen is launching the drug in another 25 markets.
The drugmaker is taking steps to educate clinicians to grow Lumakras sales in second-line therapy, and Gordon believes confirmation of therapeutic efficacy in Phase III trials will make it easier to promote. The FDA granted accelerated approval to Lumakras based on data from a single arm of the CodeBreak 100 trial where it showed an objective response rate of 36 percent and a disease control rate of 81 percent.
Full approval will hinge on results of the Phase III CodeBreak 200 trial comparing Lumakras against docetaxel in a larger patient population. That study, involving 345 patients with previously treated, advanced, and unresectable metastatic KRAS G12C-mutated NSCLC, is on track to read out in the third quarter. David Reese, Amgen's executive VP of R&D, said the trial has 90 percent power to detect a significant difference in progression-free survival. Reese said that if the trial results are "consistent with what we've observed across the program to date in advanced lung cancer, we'll be well positioned there."
As Amgen is gathering confirmatory data in the second-line setting, it is also working to move Lumakras into the first-line metastatic NSCLC space with the initiation of a new Phase III study of Lumakras plus chemotherapy.
Meanwhile, Lumakras' closest competitor is Mirati's adagrasib. Mirati presented results from its KRYSTAL-1 Phase I/II trial of adagrasib as a second-line treatment for KRAS G12C-mutated NSCLC at the American Society of Clinical Oncology's annual meeting in June. Those results showed that 43 percent of 112 patients responded — slightly better than the around 36 percent response rate among 124 patients reported for Lumakras. Median progression-free survival was 6.5 months for adagrasib and 6.8 months for Lumakras, and median overall survival was 12.6 months and 12.5 months, respectively.
Given the similar results, the sponsors are eager to differentiate their products and one way to do so is in combination with other drugs. In this regard, all eyes are on initial data from a CodeBreak-100 cohort exploring Lumakras with Merck's Keytruda (pembrolizumab), due to be reported at the World Conference on Lung Cancer on Sunday.
Ahead of the upcoming readout, however, Amgen's management appeared to be tempering expectations. Reese said that although the company would not discuss the data before the Aug. 7 embargo date for the upcoming conference, "what we can say is that PD-1 [inhibitors] have been challenging to combine with other targeted agents due to tolerability issues. … As a reminder, we are investigating multiple potential paths to first-line treatment of non-small cell lung cancer with Lumakras potentially segmented by PD-L1 expression levels."
A biomarker-informed strategy would mean breaking down the NSCLC population into three groups according to their high, low, or negative PD-L1 expression status. "We've seen some promising early data in the PD-L1-negative population," Reese said, adding that the company would "outline plans for further development in this space" after the data are released.
At the WCLC meeting, Amgen is also presenting results from a CodeBreak-100 cohort exploring Lumakras in combination with Revolution Medicines' SHP2 inhibitor RMC-4630. That group includes 21 patients with previously treated solid tumors, 11 with NSCLC, six with colorectal cancer, and four with other solid tumors.
In an abstract shared ahead of the meeting, Amgen reported that the rate of confirmed partial responses among the NSCLC patients was 27 percent and that seven of the patients achieved disease control. All four of the KRAS G12C inhibitor naïve patients had disease control. Five out of the six CRC patients achieved disease control and one patient with ovarian cancer had a confirmed partial response. Amgen said that Lumakras-RMC-6430 combination was safe and tolerable and that it is planning a dose expansion study to further explore efficacy and safety in both KRAS G12C inhibitor-naïve and -exposed NSCLC patients.
Meanwhile, the company provided an update on its precision oncology pipeline asset bemarituzumab, a monoclonal antibody targeting FGFR2b. A final analysis in the Phase II FIGHT study of bemarituzumab with FOLFOX6 in patients with previously untreated advanced gastric and gastroesophageal junction cancer was consistent with previous results showing improvements in clinical outcomes for patients with FGFR2b-expressing tumors. Greater survival benefits were also observed in patients with higher FGFR2b expression levels.