On April 25, Lilly announced that it is advancing the global withdrawal of the new soft tissue sarcoma drug Lartruvo (olaratumab). Lilly’s decision was mainly due to the fact that in the large phase III ANNOUNCE study after marketing, olaratumab failed to show survival benefit in both the treated population and the leiomyosarcoma subgroup.
Lilly also announced that it has also initiated a withdrawal response plan to ensure that the impact of Lartruvo withdrawal on current patients is minimized. For example, patients receiving Lartruvo treatment can communicate with their attending physicians, who are fully aware of Lartruvo’s risks and The results of the ANNOUNCE study, in line with the government’s legal and drug regulatory requirements, are determined by the patients themselves to decide whether to continue to receive Lartruvo treatment. In addition, new patients are no longer eligible for Lartruvo treatment except for patients who are participating in the Lartruvo clinical trial. The details of the program will be published to clinicians in the coming weeks.
Olaratumab is a monoclonal antibody that targets the platelet-derived growth factor receptor (PDGFR). Olaratumab combined with doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma was approved by the FDA on October 19, 2016. It is the first new drug approved by the FDA for soft tissue sarcoma for more than 40 years. In the same year, Lartruvo also received conditional approval from the European Union.
The FDA’s current approval decision was based on a phase II JGDG study involving 133 people. The olaratumab plus doxorubicin treatment group showed significant clinical benefit in patients with advanced soft tissue sarcoma who were unsuitable for surgery and radiation therapy. The PFS (6.6 vs 4.1 months), OS (26.5 vs 14.7 months), and ORR (18.2% vs 11.9%) were significantly improved in the patients compared with the doxorubicin monotherapy group.
However, in accordance with FDA regulations, new drugs that are marketed by accelerated approval will be subject to confirmatory research after listing. If the clinical data of the post-marketing study does not support the FDA’s initial approval decision, the new drug may be withdrawn by the FDA. Unfortunately, ANNOUNCE as a confirmatory phase III study failed to continue to support the clinical survival benefit of olaratumab in small JGDG studies.
Preliminary results of the ANNOUNCE study published on January 18 this year showed that Lartruvo combined with doxorubicin did not differ significantly in the survival (OS) of patients with prolonged soft tissue sarcoma compared with doxorubicin alone (20.4 vs 19.7 months). The PFS is even less than the latter (5.4 vs 6.8 months). The detailed results of the ANNOUNCE study will be announced at the ASCO2019 conference.
On the day the ANNOUNCE study was published, Lilly also felt very surprised and disappointed. Anne White, head of the oncology business, said at the time that “the detailed clinical data will be carefully analyzed, the differences between the two clinical studies will be found, and the global regulatory agencies will be communicated to determine the next fate of Lartruvo.”
On January 23, the European Medicines Agency posted a news on its official website recommending that doctors not prescribe Lartruvo to new patients. Patients who are currently receiving Lartruvo treatment may consider continuing to use if they show clinical benefit. About 1000 patients in Europe are currently receiving Lartruvo.
After Lilly’s announcement of Lartruvo’s global withdrawal decision, Anne White also called on patients and doctors to understand their “de-commissioning plan” at this critical time, in order to ensure that patients who are receiving Lartruvo treatment are not forcibly interrupted. Treatment, so that patients and doctors do not feel abandoned.
From the perspective of Lilly’s performance growth, the withdrawal of Lartruvo is a big loss. In 2018, Lartruvo’s global sales revenue was $305 million, an increase of 50%, which is an important driver of the Lilly tumor business.
Soft tissue sarcoma is a malignant tumor originating from tissues such as fat, fascia, muscle, fiber, lymph and blood vessels, and is very rare and refractory. For the past decades, there has been no first-line therapy to improve the survival of patients with soft tissue sarcoma. According to the American Cancer Society, there were 12,750 newly diagnosed cases and more than 5,000 deaths in the United States in 2019.
Olaratumab is also one of the first clinically urgently needed drugs published by CDE. The reason is: the incidence of soft tissue sarcoma is low, 2.63/100,000, the prognosis is poor, and the median survival of patients with advanced disease is about 1 year, and there is no effective treatment. Lilly will start the global withdrawal of the work, and olaratumab will also be completely out of China.