FDA Approves Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer

Takeda announced the U.S. Food and Drug Administration (FDA) has approval of  Fruzaqla™ (fruquintinib), an oral targeted therapy for adults with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. Fruzaqla is the first and only selective inhibitor of all three VEGF receptor kinases approved in the U.S. for previously treated mCRC regardless of biomarker status.1,2 This approval was received under Priority Review more than 20 days ahead of the scheduled PDUFA date of November 30, 2023.

"There is a pressing need for new treatments for individuals with metastatic colorectal cancer, who have had limited options and continue to face poor outcomes. Fruzaqla is the first novel chemotherapy-free treatment option approved for patients in the U.S. regardless of biomarker status in more than a decade,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. “For far too long, healthcare providers and patients have had limited options when selecting a therapy for metastatic colorectal cancer. Fruzaqla has the potential to offer a significant survival benefit to patients without negatively impacting their quality of life.”

The approval of Fruzaqla is based on data from two large Phase 3 trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, along with the FRESCO trial conducted in China, data from which were published in JAMA. The trials investigated Fruzaqla plus best supportive care versus placebo plus best supportive care in patients with previously treated mCRC. Both FRESCO and FRESCO-2 met their primary and key secondary efficacy endpoints and showed consistent benefit among a total of 734 patients treated with Fruzaqla. Safety profiles were consistent across trials.

“Patients with metastatic disease are often fragile and fatigued – due to both their condition as well as the therapies they have been exposed to. An oral, chemotherapy-free option that offers a survival benefit despite treatment with prior therapies is a critical need for treating metastatic colorectal cancer,” said Cathy Eng, M.D., FACP, at Vanderbilt University Medical Center. “Colorectal cancer is a highly heterogeneous disease, making it difficult to bring advancements to patients whose cancer has metastasized. I look forward to being able to offer a new solution to appropriate patients.”

In the United States, approximately 153,000 new cases of CRC will be diagnosed in 2023, representing 7.8% of all new cancer cases.3,4 Approximately 70% of patients with CRC will experience metastatic disease, whether at diagnosis or after treatment. Metastases are the main cause of CRC-related mortality.

“We have witnessed firsthand the physical and emotional toll metastatic colorectal cancer has on patients, their families and their care teams,” said Michael Sapienza, Chief Executive Officer, at Colorectal Cancer Alliance. “We are encouraged to see the continued progress in providing new options to patients.”

Ref ; https://en.wikipedia.org/wiki/Fruquintinib

FDA Approves Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer

FDA Approves Lytgobi (futibatinib) for Previously Treated, Unresectable, Locally Advanced or Metastatic Intrahepatic Cholangiocarcinoma

Taiho Oncology, Inc. and Taiho Pharmaceutical Co., Ltd. announced today that the U.S. Food and Drug Administration (FDA) has approved Lytgobi tablets for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

“Lytgobi is an effective, well-tolerated therapy for patients with intrahepatic CCA that can be taken orally,” said Tim Whitten, President and CEO of Taiho Oncology, Inc. “This approval is an important milestone for patients and may provide hope for improved outcomes. As someone whose family has been impacted by cholangiocarcinoma, I’m acutely aware of the impact this disease can have on the patient and their loved ones.”

As a whole, cholangiocarcinoma is an aggressive cancer of the bile ducts and is diagnosed in approximately 8,000 individuals each year in the U.S.1 This includes both intrahepatic (inside the liver) and extrahepatic (outside the liver) forms of the disease. Approximately 20% of patients diagnosed with CCA have the intrahepatic form of the disease.2,3 Within this 20%, approximately 10-16% of patients have FGFR2 gene rearrangements, including fusions, which promote tumor proliferation.4,5,6,7,8 Lytgobi covalently binds to FGFR2 and inhibits the signaling pathway.9 The other approved FGFR inhibitors are reversible ATP-competitive inhibitors.10,11,12

“Lytgobi is a key example of the potential of precision medicine in iCCA and represents another advance in the treatment of this rare and challenging disease,” said medical oncologist Lipika Goyal, MD, MPhil, of the Massachusetts General Hospital Cancer Center and lead investigator of the pivotal study that led to the approval of Lytgobi. “I am encouraged that treatment options continue to expand and evolve for this disease through the dedicated efforts of many over several years.”

The approval of Lytgobi is based on the results of the primary analysis of the FOENIX*-CCA2 trial, a global Phase 2 open-label trial evaluating 103 patients with unresectable, locally advanced or metastatic iCCA harboring FGFR2 gene rearrangements including fusions. In this trial, patients received Lytgobi orally once daily at a dose of 20mg until disease progression or unacceptable toxicity.

The trial met its primary endpoint with an objective response rate of 42% as measured by independent central review. The median duration of response (DOR) was 9.7 months, with 72% of responses lasting at least six months. The most common (≥20%) adverse reactions were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, dry skin, arthralgia, dysgeusia, abdominal pain, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Lytgobi was discovered by Taiho Oncology’s parent company, Taiho Pharmaceutical, which continues to co-develop this product for other potential tumor types. “The Taiho group is working as one to optimize this agent for the patients who are waiting,” said Teruhiro Utsugi, Senior Managing Director at Taiho Pharmaceutical.

https://en.wikipedia.org/wiki/Futibatinib