In its 15th year, Verastem Oncology has gained its first FDA approval, winning an accelerated nod for the combination treatment of avutometinib and defactinib for a rare form of ovarian cancer.
With the commercial name of Avmapki Fakzynja Co-Pack, the combo becomes the first treatment specifically for patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC). It affects between 6,000 and 8,000 women in the U.S. and 80,000 globally.
Verastem believes Avmapki Fakzynja Co-Pack is the first-ever oral combo therapy of two novel drugs approved in oncology and is destined to replace chemotherapy as the standard of care for LGSOC.
The Thursday nod—which covers patients who have already received systemic therapy—came coincidentally on World Ovarian Cancer Day and was more than seven weeks ahead of its June 30 FDA target decision date.
“We’ve been working to do this for a long time,” Verastem CEO Dan Paterson said during a conference call. “We’ve had the pleasure of getting embedded into the patient community here and have just thoroughly enjoyed the ability to be able to offer something for these patients that haven’t had anything before.”
The Needham, Massachusetts-based company will charge $48,500 for a 28-day regimen of the treatment, which includes two 3.2 mg doses per week of Avmapki and two daily 200 mg doses of Fakzynja. Patients are on therapy for an average of 18 months.
“It’s difficult when you’re pricing two novel-novel therapies simultaneously to get true analogs but if you look at the recent approvals across rarer indications in oncology, prices have ranged somewhere between $45,000 to $55,000,” Mike Crowther, Verastem’s chief commercial officer, said on the call.
Verastem said it is ready to provide Avmapki Fakzynja Co-Pack next week and expects a gradual initial launch trajectory, according to Paterson. The company said that roughly half of the patients who have been diagnosed are concentrated in 100 centers.
Mizuho Securities analyst Graig Suvannavejh, Ph.D., has pegged peak sales in the indication at between $700 million and $900 million. He noted that the combo has also shown promise in an early-stage trial for first-line pancreatic cancer.
Focused on developing cancer drugs that target cancer stem cells, Verastem was co-founded in 2010 by investors Christoph Westphal and Michelle Dipp and was created to commercialize research from MIT biologists Piyush Gupta, Eric Lander and Robert Weinberg.
Two years later, in an agreement with Pfizer, Verastem in-licensed worldwide commercial rights to focal adhesion kinase (FAK) inhibitor defactinib. FAK is a non-receptor tyrosine kinase that regulates tumor cell proliferation and invasion. Targeted disruption of this pathway in preclinical models had shown reductions in primary tumor mass and metastasis.
In 2016, Verastem gained rights to RAF/MEK inhibitor avutometinib from Pfizer and Merck KGaA, specifically to pair it up with defactinib, which had flunked an early-stage trial in mesothelioma.
“In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK,” Verastem said in a release. “This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors.”
Verastem did not reveal the regulatory milestones it will pay Pfizer for defactinib, but chief financial officer Dan Calkins did say that it will pay royalties of “high-single digits to low-double digits” on the treatment. While there are no milestones on avutometinib, according to Calkins, Roche’s Chugai Pharmaceutical will receive royalties “in the double-digit range,” he said.
The approval of Avmapki Fakzynja Co-Pack was based on the tumor response rate and duration of response demonstrated in a phase 2 trial of 57 patients who had received at least one prior systemic therapy, including a platinum-based regimen. Verastem is running a confirmatory phase 3 trial, RAMP 301, pitting the combo against standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC with and without a KRAS mutation.
LGSOC makes up only about 2% to 5% of all cases of ovarian cancer. The disease skews toward a younger population and approximately 80% of patients experiencing recurrence after remission. The disease has a high mortality rate, with a median survival of around 10 years.