Eli Lilly Announces Global Withdrawal of Olaratumab (Lartruvo) Following Phase III ANNOUNCE Trial Failure

CitePharmaceuticalsMoFang’s Report: Yesterday (April 25), Eli Lilly announced that it is advancing the global market withdrawal of Lartruvo (olaratumab), a new drug for advanced soft tissue sarcoma, while simultaneously launching a withdrawal response plan to minimize the impact on current patients. For instance, patients currently receiving Lartruvo may discuss with their attending physicians whether to continue treatment, based on their own informed decisions, provided they fully understand the risks associated with Lartruvo and the results of the ANNOUNCE study, and comply with applicable national laws and pharmaceutical regulatory requirements. Furthermore, except for patients already enrolled in Lartruvo clinical trials, new patients are no longer permitted to receive Lartruvo treatment. Detailed guidelines regarding this protocol will be released to clinicians in the coming weeks.

It is reported that Eli Lilly withdrew Lartruvo from the market due to its failure in Phase III clinical trials. Lartruvo is a platelet-derived growth factor receptor alpha (PDGFR-α) blocking antibody that specifically binds to PDGFR-α and prevents receptor activation. On October 19, 2016, the FDA granted accelerated approval for Lartruvo in combination with doxorubicin for the treatment of adult soft tissue sarcoma (STS). This was the first new drug approved for the initial treatment of unresectable and non-radiatable STS in nearly 40 years since the approval of doxorubicin. Doxorubicin is currently the only monoclonal antibody that specifically binds to platelet-derived growth factor receptor alpha (PDGFR-α). Previously, the most common treatment for such patients was doxorubicin monotherapy or in combination with other drugs.

The approval at that time was based on an open-label, randomized, active-controlled Phase II clinical trial named JGDG, which was conducted in 133 patients with metastatic soft tissue sarcoma (STS) of various subtypes. The trial comprised two groups: the LARTRUVO plus doxorubicin group (N=66) and the doxorubicin group (N=67). All patients received doxorubicin at a dose of 75 mg/m² on Day 1. Patients in the LARTRUVO plus doxorubicin group additionally received LARTRUVO at a dose of 15 mg/kg on Days 1 and 8, with each cycle lasting 21 days.

This trial evaluated the length of patient survival after treatment (overall survival, OS), the time to tumor progression after treatment (progression-free survival, PFS), and the percentage of patients with tumor shrinkage (overall response rate, ORR). The final clinical results demonstrated a statistically significant improvement in OS for patients in the combination therapy group: the median overall survival was 26.5 months, compared with 14.7 months for patients receiving doxorubicin monotherapy. The median progression-free survival was 8.2 months in the combination therapy group versus 4.4 months in the doxorubicin monotherapy group. The overall response rate was 18.2% in the combination therapy group, compared with only 7.5% in the doxorubicin monotherapy group.

These data directly led to the U.S. FDA granting it accelerated approval, and the European Medicines Agency also approved its conditional marketing authorization.

However, in accordance with FDA regulatory requirements, new drugs approved via the accelerated approval pathway must conduct confirmatory studies post-marketing. If the clinical data from post-marketing studies fail to support the FDA’s initial approval decision, the drug may be withdrawn from the market by the FDA. Unfortunately, the Phase III ANNOUNCE trial failed to demonstrate that Lartruvo in combination with doxorubicin provided greater clinical benefit compared to doxorubicin monotherapy.

At that time, Anne White, President of Eli Lilly, stated that the company was surprised and disappointed that Lartruvo failed to improve survival rates in patients with advanced soft tissue sarcoma. Eli Lilly has always been committed to helping individuals affected by soft tissue sarcoma, and we will carefully review the detailed data to better understand the differing outcomes between the two trials.

However, what ultimately came was the global withdrawal of Lartruvo from the market.

It is also worth noting that Lartruvo was included in the “First Batch of Overseas New Drugs Urgently Needed for Clinical Use” published by China last year. This meant that there were no ethnic differences associated with Lartruvo, allowing its overseas clinical data to be directly used to submit a marketing application to China’s National Medical Products Administration (NMPA). However, the recent global withdrawal of Lartruvo has ultimately made it unavailable to Chinese patients.

Some analysts believe that the withdrawal of Lartruvo from the market represents a significant loss for Eli Lilly and Company. According to data from the Prescription Drug Database (PDB), Lartruvo’s sales grew nearly 18-fold, rising from $9.4 million in 2016 to $180 million in 2017. In 2018, global sales further reached $305 million, marking an increase of nearly 50% compared to 2017.