NEW YORK – Results from a pivotal Phase III trial comparing EQRx's third-generation EGFR inhibitor, aumolertinib, to AstraZeneca's first-generation Iressa (gefitinib), adds to the body of evidence supporting the newer drug as a first-line option for patients with EGFR-mutated non-small cell lung cancer.
Aumolertinib was developed by Shanghai-based Hansoh Pharmaceutical Group and is already marketed in China as a second-line therapy for patients with advanced NSCLC and an EGFR T790M resistance mutation. Vincent Miller, EQRx physician-in-chief, said that at the time the AENEAS trial was initiated in 2019 by Hansoh, Iressa was the standard-of-care therapy in that setting.
In EQRx's Phase III trial, data from which were published in the Journal of Clinical Oncology this week, aumolertinib nearly doubled median progression-free survival in patients to 19.3 months compared to 9.9 months for those on Iressa. Patients on aumolertinib had a 54 percent lower risk of disease progression or death compared to patients on Iressa. The PFS benefit included patients stratified by the presence or absence of central nervous system metastases, which are a significant cause of morbidity and mortality in NSCLC patients. EQRx plans to present data from patients with CNS metastases at the American Society of Clinical Oncology's annual meeting in June.
Aumolertinib was also associated with significantly lower rates of rash and diarrhea compared to Iressa, which was a bonus advantage of the newer drug. "We believe this benefit could be important for patients, their families, and healthcare professionals, as these burdensome and uncomfortable side effects can affect the quality of life for people being treated for NSCLC," said Miller. EQRx and Hansoh will discuss the latest aumolertinib data with regulators in multiple countries, and are planning to seek approval for the drug as a first-line treatment for EGFR-mutated advanced NSCLC outside the US later this year.
Aumolertinib's edge over Iressa is likely attributable to its ability to target both EGFR-sensitizing and T790M resistance mutations, with high selectivity over wild-type EGFR, according to the Cambridge, Massachusetts-based company. "T790M mutations are common mutations that can lead to resistance against the older generation of EGFR inhibitors," said Miller.
Head-to-head trials like AENEAS are part of an overall competitive pricing strategy that EQRx is pursuing for all of its products. The company launched in 2020 with a mission to reduce the cost of medicines. By making a favorable comparison to competing products in terms of efficacy and toxicity, EQRx can reassure doctors, patients, and payors of the value of drugs that it hopes to sell at a fraction of competitors' prices.
"We believe it's important to demonstrate that comparability, even after safety and efficacy have been demonstrated," because, Miller said, many Americans have been raised to believe that if a product costs less, it must not be as good. "That's really where we have to reassure all of the stakeholders that what we say we're delivering on, we're truly delivering."
Industry players tend to shy away from head-to-head trials because they're risky. After all, if a company's own drug fails to show it is equivalent or superior to a competitor's, it can be financially disastrous, especially in competitive and crowded markets like non-small cell lung cancer. That's why Hansoh and EQRx did their homework to de-risk the trial before it started, by analyzing data from earlier studies. Miller said that if he'd been asked before the trial started, "I would have humbly said, 'I think that trial has a chance to be successful.'"
Meanwhile, if aumolertinib reaches the market, it will compete with third-generation drugs, like AstraZeneca's Tagrisso (osimertinib), which is the current standard of care with demonstrated anti-tumor activity in metastatic NSCLC patients with EGFR sensitizing and resistance mutations. For that reason, aumolertinib's demonstrated superiority over a first-generation drug like Iressa may be less relevant to current treatment practices.
Miller said EQRx is on track to initiate a randomized, open-label trial comparing aumolertinib against Tagrisso in first-line EGFR-mutated NSCLC. That trial will involve a diverse cohort of patients and divide them into three groups receiving aumolertinib, aumolertinib plus chemotherapy, or Tagrisso.
Ultimately, EQRx's aim is to realign the incentives for drug manufacturers, doctors, payors, and patients, which it believes are currently at odds with each other. "The doctor has to battle for the patient to get the drug approved by the payor, in many cases," said Miller. "The patient is waiting in the background to start this therapy and may first hear the startling news it was denied [coverage] or they recommended [another] drug instead."
According to Miller, the widely cited $3 billion to $5 billion cost for a cancer drug to be developed is largely attributable to other drugs in a company's pipeline that fail in preclinical development, commercialization costs, and marketing.
"We believe that in 2022, with our advances in chemistry, biochemistry, genomics, proteomics, and artificial intelligence, the cost of drug development should be substantially less than it is, particularly in areas that are most expensive, like oncology and immune-inflammatory diseases," said Miller, noting that these pricing advantages should be achievable for drug classes with well-studied mechanisms of action and validated targets, like EGFR inhibitors.
With reduction in development costs, EQRx believes it can price its drugs at a "fraction" of what other companies typically charge, particularly in the US, and still make a profit.
EQRx has already started inking agreements with payors and health systems, allowing them to secure access to its drugs at lower costs. The company has memoranda of understanding with CVS Health, the National Health Service in England, Geisinger, Blue Shield of California, and other health plans.
While EQRx is planning to launch aumolertinib in the highly competitive and established EGFR-mutated NSCLC market, the company is also hoping to expand the drug into new biomarker-defined indications.
The firm recently said that Turning Point Therapeutics plans to begin a Phase Ib/II trial of its MET-targeting drug elzovantinib with aumolertinib in patients with EGFR-mutated and MET-amplified advanced NSCLC. According to the companies, up to 20 percent of NSCLC patients with EGFR-mutated tumors become resistant to therapy after acquiring MET amplifications, and they are hoping to overcome that resistance with this combination.