Accelerating FDA approval makes Verastem drug the first treatment for rare types of ovarian cancer
Now, a rare ovarian cancer that grows slowly and responds poorly to chemotherapy, is now an FDA-approved treatment, a combination drug developed by Verastem oncology that addresses the pathways that drive tumor progression.
The approval announced Thursday covers the treatment of low-grade serous ovarian cancer (LGSOC) driven by a KRAS mutation in adults who received a previously systemic treatment. Verastem drugs are paired with two small molecules taken separately and will be sold under the brand name Avmapki Fakzynja. Verastem expects its new product to be launched next week.
There are several different types of ovarian cancer. Advanced serous ovarian cancer (HGSOC) is the most common type and is usually diagnosed in women aged 40 to 60. Surgery and chemotherapy are the standard treatments for HGSOC. By contrast, LGSOC is more rare and is usually diagnosed in young women, usually between the ages of 20 and 30 or between the ages of 50 and 60, according to Verastem. The company estimates that between 6,000 and 8,000 women in the United States have LGSOC, with 1,000 to 2,000 cases diagnosed each year. After diagnosis, the median patient was 10 years. Surgery, chemotherapy and off-label use of hormone therapy are standard treatments for LGSOC. However, this type of cancer responds poorly to these treatments and recurrence is common.
It is estimated that 70% of LGSOC tumors are driven by mutations in the MAPK pathway that regulates certain processes, such as cell growth. Mutations in genes such as RAS and MEK can lead to dysregulation of this pathway, which leads to the growth of cancer cells. The RAS gene family has long been impossible. In 2021, Amgen's Lumakras became an FDA-approved KRAS inhibitor. This daily drug is approved for the treatment of non-small cell lung cancer driven by KRAS G12C mutations.
The Avutometinib component of Verastem drug combination is a small molecule inhibitor of the MEK protein that can overactivate the RAS/MAPK pathway when mutated. The Defactinib component of the Verastem drug is a small molecule inhibitor of two members of the FAK protein, which plays a role in the growth, spread and survival of cancer cells. According to Verastem, this combination is intended to more fully block abnormal signaling, thereby driving cancer growth and drug resistance in tumors dependent on the RAS/MAPK pathway.
Verastem evaluated the drug combination in a pivotal phase 2 study, including 57 adults with measurable recurrent LGSOCs with KRAS mutations. Participants in the open-label study had at least one previous systemic therapy, including platinum-based chemotherapy. During the first three weeks of each four-week treatment cycle, Avutometinib was taken twice a week and Defactinib twice a day. The results show that the overall response rate is 44%. The response duration ranges from 3.3 months to 31.1 months. Severe complications reported by the study include eye, skin and hepatotoxicity.
The regulatory decision announced Thursday was accelerated approval under a pathway that could allow drugs to be brought to market faster with little or no treatment available. Drugs approved under this faster route must be confirmed in a larger phase 3 study of their safety and efficacy. This confirmatory study is underway; Verastem is expected to complete admission by the end of this year.
“The approval of avutometinib plus defactinib brings a much-needed therapeutic option to patients and establishes this combination as the new standard of care for women with recurrent low-grade serous ovarian cancer harboring a KRAS mutation,” Dr. Rachel Grisham, section head, ovarian cancer at Memorial Sloan Kettering Cancer Center, and global lead principal investigator of the Verastem drug's clinical trials, said in a statement Approval announcements included in the company. “I look forward to conducting a confirmatory phase 3 trial, ramp 301, and we hope to continue supporting the ongoing study of this combination in women with and without KRAS mutations.”
Verastem said that in addition to supporting the full approval of LGSOC, the third phase of the study could support the extension of drug combinations to treatments for LGSOC regardless of KRAS mutation status. Verastem said investigator-sponsored clinical trials are evaluating drug combinations in other gynecological cancers driven by mutations in the MAPK pathway. Intermediate-term studies are also constantly evaluating drug combinations for non-small cell lung and pancreatic cancer.
Verastem reported its cash position of $88.8 million as of the end of 2024. The company has since taken steps to strengthen its financial position in preparation for the commercialization of Avmapki Fakzynja co-package. Verastem received up to $150 million in debt financing in January; the company raised $75 million in private securities investment in the second half of last month.
Photo by Verastem Oncology
