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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Friday, March 06, 2015

The U.S. Food and Drug Administration has today approved Zarxio (filgrastim-sndz), a biosimilar to filgrastim (Neupogen, marketed by Amgen Inc.). Neupogen binds to the granulocyte colony-stimulating factor (G-CSF) receptor, and is widely prescribed to treat neutropenia. The approval of Zarxio is the first biosimilar product approved in the U.S.

 

Zarxio is approved for the same indications as Neupogen, which are:

·         For patients with cancer receiving myelosuppressive chemotherapy;

·         For patients with acute myeloid leukemia receiving induction or consolidation chemotherapy;

·         For patients with cancer undergoing bone marrow transplantation;

·         For patients undergoing autologous peripheral blood progenitor cell collection and therapy; and

·         For patients with severe chronic neutropenia.

 

“Biosimilars will provide access to important therapies for patients who need them,” FDA Commissioner Margaret A. Hamburg, MD, said in a news release. “Patients and the health care community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy, and quality standards.”

 

In a unanimous vote earlier this year, the Oncologic Drugs Advisory Committee to the FDA had recommended that the agency approve the biosimilar based on its safety and efficacy data, as well as evidence of the benefits of its use in more than 40 countries outside of the U.S. over the past 20 years (OT 2/10/15 issue).

 

Approval Process

A biosimilar product is a biological product—derived from a living organism including humans, animals, mircroorganisms, or yeast—that is approved based on a showing that it is highly similar to an already-approved biological product, known as a reference product. The biosimilar must also show it has no clinically meaningful differences in terms of safety and efficacy from the reference product. Only minor differences in inactive components are allowable in biosimilar products.

 

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s), and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

 

The Biologics Price Competition and Innovation Act of 2009 (passed as part of the Affordable Care Act in 2010) created an abbreviated licensure pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological product, the reference product. This abbreviated licensure pathway under section 351(k) of the Public Health Service Act permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and enables a biosimilar biological product to be licensed based on less than a full complement of product-specific preclinical and clinical data.

 

Evidence Review for Zarxio

The FDA’s approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen, according to a news release from the FDA. Zarxio has been approved as biosimilar, not as an interchangeable product. Under the BPCI Act, a biological product that that has been approved as an “interchangeable” may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.

 

In a news release from the manufacturer, Louis Weiner, MD, Chairman of the Department of Oncology and Director of the Lombardi Comprehensive Cancer Center at Georgetown University, noted: "Filgrastim has proven clinical value in treating patients at increased risk of neutropenia, but it is underused in the U.S. for a variety of reasons, including price.

 

“Biosimilars have the potential to increase access—and the approval of Zarxio may reduce costs to the health care system. The comprehensive data set supports its use in clinical practice."

 

The most common expected side effects of Zarxio are aching in the bones or muscles and redness, swelling, or itching at injection site. Serious side effects may include spleen rupture; serious allergic reactions that may cause rash, shortness of breath, wheezing, and/or swelling around the mouth and eyes; fast pulse and sweating; and acute respiratory distress syndrome.

 

Nonproprietary Naming Policy

For this approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name for this product should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilar and other biological products, noted a news release from the FDA. While the FDA has not yet issued draft guidance on how current and future biological products marketed in the United States should be named, the agency intends to do so in the near future.


Thursday, March 05, 2015

The U.S. Food and Drug Administration has expanded the approved use of Opdivo (nivolumab) for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Opdivo works by inhibiting the PD-1 pathway, which blocks the body’s immune system from attacking cancer cells.

 

The drug had previously received accelerated approved to treat patients with unresectable or metastatic melanoma who no longer respond to other drugs (OT 1/25/15 issue).

 

“The FDA worked proactively with the company to facilitate the early submission and review of this important clinical trial when results first became available in late December 2014,” Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a news release. “This approval will provide patients and health care providers knowledge of the survival advantage associated with Opdivo and will help guide patient care and future lung cancer trials.”

 

Priority Review

Opdivo was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness in the treatment of a serious condition. Opdivo has been approved more than three months ahead of its prescription drug user fee goal date when the FDA was scheduled to complete its review of the application.

 

Clinical Trial Results

Opdivo was evaluated in a randomized trial of 272 patients with squamous NSCLC. Overall survival for patients receiving Opdivo was on average 3.2 months longer than patients receiving docetaxel.

 

Additionally, safety and efficacy for the drug were evaluated in a single-arm trial of 117 patients with squamous NSCLC who had progressed after receiving a platinum-based therapy and at least one additional systemic regimen. Fifteen percent of the patients receiving the drug had their tumors shrink or disappear, and 59 percent of the patients had a response lasting six months or longer.

 

The most common side effects for Opdivo are fatigue, shortness of breath, musculoskeletal pain, decreased appetite, cough, nausea, and constipation. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys, and hormone-producing glands.

 

Opdivo is marketed by Bristol-Myers Squibb.


Monday, March 02, 2015

The U.S. Food and Drug Administration has granted orphan drug designation to Reolysin for the treatment of patients with cancer of the fallopian tube. The drug is a proprietary isolate of the reovirus that infects and selectively targets tumors with activating Ras pathway mutations and/or over-expressions of Ras pathway elements including EGFR, BRAF, KRAS, and others.

 

Reolysin was granted orphan drug status for the treatment of patients with ovarian cancers and patients with pancreatic cancers last month.

 

The Orphan Drug designation—to encourage development of drugs in the diagnosis, prevention, or treatment of a medical condition affecting fewer than 200,000 people in the U.S.—grants a product market exclusivity for a seven-year period if the sponsor complies with certain FDA specifications, as well as tax credits and prescription drug user fee waivers. The designation does not, though, shorten the duration of the regulatory review and approval process.

 

Reolysin’s orphan drug status for cancer of the fallopian tube is based on data from a Phase 1/2 clinical trial of patients with metastatic ovarian, peritoneal, or fallopian cancers using concurrent intravenous and intraperitoneal administration of Reolysin—the same trial data that supported the drug’s application for orphan drug status for ovarian cancers. A second ongoing randomized Phase II trial of weekly paclitaxel versus weekly paclitaxel with Reolysin in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer completed enrollment in September.

 

Reolysin is marketed by Oncolytics Biotech Inc.


Monday, March 02, 2015

The U.S. Food and Drug Administration has granted Fast Track designation to Epstein-Barr Virus cytotoxic T lymphocytes (EBV-CTL) for the treatment of patients with rituximab-refractory, EBV-associated lymphoproliferative disease (EBV-LPD), which can occur in patients who have had allogeneic hematopoietic cell transplantation. EBV-CTL are made from T-cells, collected from third-party and exposed to certain antigens, so that the activated T-cells can be used in an appropriate partially human leukocyte-antigen-matched patient with EBV-LPD. The activated EBV-CTL find cancer cells expressing EBV and kill them.

 

The Fast Track designation, established under the FDA Modernization Act of 1997, is designed to facilitate frequent interactions with the FDA review team to expedite clinical development and submission of a New Drug Application for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs. The designation permits the drug developer the opportunity to submit sections of an NDA on a rolling basis as data become available, allowing the FDA to review those materials on a rolling basis as well.

 

EBV-LPD is a serious complication associated with stem cell transplant that can cause life-threatening lymphomas and other cancers.

 

Breakthrough therapy designation for EBV-CTL was based on data from two separate clinical trials, including an ongoing Phase II study that is currently recruiting patients. EBV-CTL is marketed by Atara Biotherapeutics, Inc.


Tuesday, February 24, 2015

The U.S. Food and Drug Administration has approved Farydak (panobinostat) for the treatment of patients with multiple myeloma. It is intended for patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent. Farydak is to be used in combination with the chemotherapy bortezomib and the anti-inflammatory medication dexamethasone.

 

Farydak works by inhibiting the activity of histone deacetylases enzymes, which may slow the over-development of plasma cells in patients with multiple myeloma or cause the cells to die. Farydak is the first HDAC inhibitor approved to treat multiple myeloma.

 

“Farydak has a new mechanism of action that distinguishes it from prior drugs approved to treat multiple myeloma, making it a potentially attractive candidate agent for the treatment of multiple myeloma,” Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a news release. “Farydak’s approval is particularly important because it has been shown to slow the progression of multiple myeloma.”

 

In November 2014, the FDA’s Oncologic Drugs Advisory Committee advised the agency that, based on the data reviewed, the drug’s benefits did not outweigh its risks for patients with relapsed multiple myeloma. After the meeting, the company submitted additional information supporting Farydak’s use for a different indication: patients with multiple myeloma who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent.

 

Clinical Trial Results

The safety and efficacy for Farydak in combination with bortezomib and dexamethasone was demonstrated in a clinical trial of 193 patients with multiple myeloma who had received at least two prior treatments that included bortezomib and an immunomodulatory agent. The data showed that patients receiving the Farydak combination had progression-free survival for 10.6 months compared with 5.8 months for patients treated with bortezomib and dexamethasone alone. Additionally, 59 percent of the patients treated with Farydak had their cancer shrink or disappear versus only 41 percent of the patients receiving just bortezomib and dexamethasone.

 

Farydak carries a Boxed Warning alerting patients and health care professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias and electrocardiogram changes have occurred in patients receiving Farydak. Because of these risks, Farydak is being approved with a Risk Evaluation and Mitigation Strategy (REMS) consisting of a communication plan to inform health care professionals of these risks and how to minimize them.

 

The most common side effects of Farydak were diarrhea, tiredness, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting, and weakness. The most common laboratory abnormalities were hypophosphatemia, hypokalemia, hyponatremia, increased creatinine, thrombocytopenia, leukopenia, and anemia. Health care professionals should also inform patients of the risk of bleeding in the gastrointestinal tract and the lungs, and hepatotoxicity, according to the news release from the FDA.

 

Priority Review, Orphan Drug Designation, & Accelerated Approval

The FDA granted Farydak priority review and orphan product designation. Priority review provides for an expedited review of drugs that are intended to treat a serious disease or condition and may provide a significant improvement over available therapy. Orphan product designation is given to drugs intended to treat rare diseases.

 

The FDA action was taken under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. The accelerated approval program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. An improvement in survival or disease-related symptoms has not yet been established for Farydak. The company is now required to conduct confirmatory trials to verify and describe the clinical benefit of Farydak.

 

Farydak is marketed by Novartis Pharmaceuticals.

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