FDA News – November 2015

November 2015, Vol 6, No 10 - FDA Approvals, News & Updates


In This Article




Imlygic, First-of-Its-Kind Oncolytic Virus Therapy Approved for Melanoma

The first oncolytic virus therapy—talimogene laherparepvec (Imlygic; Amgen Inc/BioVex Inc), formerly known as T-VEC—was approved by the FDA for the treatment of patients with melanoma occurring in the skin or in lymph nodes (October 27, 2015).

“Melanoma is a serious disease that can advance and spread to other parts of the body, where it becomes difficult to treat,” said Karen Midthun, MD, Director of the FDA’s Center for Biologics Evaluation and Research. “This approval provides patients and health care providers with a novel treatment for melanoma.”

Talimogene laherparepvec is a genetically modified live oncolytic herpesvirus therapy. It is injected into the melanoma lesions, where it replicates within cancer cells and kills them. This virus therapy is indicated for the treatment of unresectable melanoma lesions. After the first dose, the second injection is administered 3 weeks later, followed by additional doses every 2 weeks for at least 6 months, until another treatment is needed or until all lesions have been killed.

The safety and efficacy of talimogene laherparepvec were evaluated in a multicenter study involving 436 patients with metastatic unresectable melanoma. Patients were randomized to talim­ogene laherparepvec or to a comparator therapy for at least 6 months or until all melanoma lesions were destroyed.

Overall, 16.3% of the patients who received the new virus therapy had reductions in the size of their melanoma lesions that lasted ?6 months versus 2.1% of the patients receiving the comparator therapy. However, talimogene laherparepvec did not improve overall survival, nor did it have any impact on melanoma that metastasized to the brain, bone, liver, lungs, or other internal organs.

The most common side effects associated with talimogene laherparepvec were fatigue, chills, fever, nausea, flulike symptoms, and injection site pain. In addition, because talimogene laherparepvec is a modified live oncolytic herpesvirus therapy, patients can be infected with this disease; therefore, this virus therapy should be avoided in patients with suppressed immune systems or in pregnant patients.

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Yondelis a New Treatment Option for Patients with Soft-Tissue Sarcoma

The FDA approved the new chemotherapy trabectedin (Yondelis; Janssen) for the treatment of patients with 2 types of unresectable or metastatic soft-tissue sarcomas, liposarcoma and leiomyosarcoma. Trabectedin is indicated for patients who previously received chemotherapy that contained anthracycline (October 23, 2015).

Soft-tissue sarcomas involve cancer cells that form in soft tissues in the body, including muscles, tendons, fat, blood vessels, lymph vessels, nerves, and tissues around joints. Liposarcoma occurs in fat cells, and leiomyosarcoma occurs in smooth muscle cells. Soft-tissue sarcoma is most common in the head, neck, arms, legs, trunk, and abdomen.

“The treatment of advanced or metastatic soft-tissue sarcoma represents a difficult challenge with few effective therapeutic choices available for patients,” said Richard Pazdur, MD, FDA’s Director of the Office of Hematology and Oncology Products. “Today’s approval of Yondelis provides a treatment option for advanced or metastatic liposarcoma and leiomyosarcoma.”

The effectiveness and safety of trabectedin were based on the results of a phase 3 clinical trial that included 518 patients with metastatic or recurrent leiomyosarcoma or liposarcoma. Patients were randomized to trabectedin or to dacarbazine. Progression-free survival was 4.2 months versus 1.5 months, respectively. Partial responses were also more common with trabectedin than with dacarbazine, but no group had complete responses.

The most common adverse events with trabectedin were nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, dyspnea, headache, peripheral edema, neutropenia, thrombocytopenia, anemia, elevated liver enzymes, and reduced albumin levels. This drug carries a warning box about the risk for neutropenic sepsis, rhabdomyolysis, hepatotoxicity, extravasation, tissue necrosis, and cardiomyopathy.

Trabectedin is already approved in Europe for soft-tissue sarcoma and for ovarian cancer.

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Onivyde Receives Expedited Approval for Metastatic Pancreatic Cancer

Using its priority review process, the FDA approved irinotecan liposome injection (Onivyde; Merrimack Pharmaceuticals Inc), for use in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic pancreatic cancer who have received previous therapy with gemcitabine (Gemzar)-based chemotherapy (October 22, 2015).

Pancreatic cancer can be difficult to diagnose early, and the treatment options are limited, especially for metastatic disease.

“Many FDA staff who review drug applications are clinicians as well, so it’s especially rewarding when we are able to expedite access to new treatments for patients with unmet needs,” said Dr Pazdur. “By using the Priority Review designation for the application for Onivyde, patients will have earlier access to a drug that helps extend survival.” The FDA also granted an orphan drug designation for irinotecan liposome injection.

This approval is based on a randomized, open-label study of 417 patients with metastatic pancreatic cancer that progressed after chemotherapy with gemcitabine or a gemcitabine-based therapy. Overall survival was an average of 6.1 months with the combination of irinotecan liposome injection plus fluorouracil and leucovorin compared with 4.2 months with fluorouracil plus leucovorin without irinotecan liposome. No survival benefit was seen for patients who received irinotecan liposome without the combination of fluorouracil plus leucovorin.

In addition, patients receiving the 3-drug combination had a delay in progression-free survival (PFS): the mean PFS was 3.1 months with the 3-drug combination compared with 1.5 months with fluorouracil and leucovorin alone.

The most common side effects of irinotecan liposome were diarrhea, fatigue, vomiting, nausea, decreased appetite, stomatitis, and fever. The drug also resulted in lymphopenia and neutropenia; death caused by sepsis from neutropenia has been reported with irinotecan liposome.

Irinotecan liposome injection is approved with a boxed warning about the risks for severe neutropenia and diarrhea. The new drug is not approved to be used alone for this indication.

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Abemaciclib Receives Breakthrough Therapy Status for Refractory Metastatic Breast Cancer

The FDA granted a breakthrough therapy designation to abemaciclib (LY2835219; Eli Lilly and Company), a cyclin-dependent kinase (CDK)4 and CDK6 inhibitor, for patients with refractory, hormone receptor (HR)-­positive metastatic breast cancer (October 8, 2015).

Cyclin-dependent kinases are involved in regulating cell cycle progression; uncontrolled cell growth plays a role in many cancers and results from an increased signaling from CDK4 and CDK6. Abemaciclib is designed to block cancer-cell growth by inhibiting CDK4 and CDK6. However, the results from cell-free enzymatic assays have shown that abemaciclib was most active against cyclin D1 and CDK4.

The FDA granted the breakthrough therapy designation based on data presented in 2014 from the breast cancer cohort expansion of a phase 1 clinical trial investigating the safety and efficacy of abemaciclib in patients with advanced or metastatic breast cancer. Patients in this cohort received a median of 7 systemic treatments before receiving abemaciclib.

“If caught before it spreads, patients can survive breast cancer. However, for the nearly 10 percent of patients who are initially diagnosed at stage IV, and the nearly 30 percent of patients whose early-stage cancer will re-occur as metastatic disease, there remains an urgent need for effective therapy options,” said Richard Gaynor, MD, Senior Vice President of Product Development and Medical Affairs for Lilly Oncology.

Abemaciclib is currently being investigated in 2 phase 3 clinical trials of patients with HR-positive breast cancer and in 1 phase 3 trial in patients with lung cancer.

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Opdivo Gets Second Indication for Metastatic Lung Cancer

For the second time this year, the FDA expanded the indication of nivolumab (Opdivo; Bristol-Myers Squibb) for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) that is progressing during or after the use of platinum-based chemotherapy (October 8, 2015). In March 2015, the FDA approved niv­o­lumab for the treatment of patients with squamous NSCLC. In this second approval in October, the FDA expanded the indication for nivo­lumab to include patients with non-squamous NSCLC.

Nivolumab was the first immunotherapy to be approved for the treatment of patients with lung cancer. It works by blocking the PD-1/PD ligand 1 (PD-L1) immune-cell pathway.

“There is still a lot to learn about the PD-1/PD-L1 pathway and its effects in lung cancer, as well as other tumor types,” said Dr Pazdur. “While Opdivo showed an overall survival benefit in certain non-small cell lung cancer patients, it appears that higher expression of PD-L1 in a patient’s tumor predicts those most likely to benefit.”

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