Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to trastuzumab deruxtecan for the treatment of HER2-positive metastatic breast cancer; granted Fast Track designation for bemcentinib for elderly patients with relapsed acute myeloid leukemia (AML); granted Breakthrough Device designation to a novel assay used for the detection of prostate cancer; and issued a statement on a new draft guidance providing proposed labeling recommendations to help ensure women receive and understand information regarding the benefits and risks of breast implants.
Priority Review for Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer
The FDA accepted for review a biologics license application for trastuzumab deruxtecan and granted the application Priority Review.
The Prescription Drug User Fee Act (PDUFA) date for trastuzumab deruxtecan, a HER2-targeting antibody drug conjugate, is set for the second quarter of 2020.
Trastuzumab deruxtecan was previously granted Breakthrough Therapy designation and Fast Track designation by the FDA. The biologics license application is based on the combination of data from a phase I trial published by Tamura et al in The Lancet Oncology and the phase II DESTINY-Breast01 trial. The response rate observed in DESTINY-Breast01, as assessed by an independent review committee, validated the clinical activity observed in the phase I trial. Detailed data from DESTINY-Breast01 will be presented at the upcoming 2019 San Antonio Breast Cancer Symposium.
DESTINY-Breast01 is an open-label, global, multicenter, two-part trial evaluating the safety and efficacy of trastuzumab deruxtecan in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine. The primary endpoint of the trial is objective response rate as determined by independent central review. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival, and overall survival. Enrollment into DESTINY-Breast01 was completed in September 2018 with 253 patients at more than 100 sites across North America, Europe, Japan, and other countries in Asia.
The safety and tolerability profile of trastuzumab deruxtecan in DESTINY-Breast01 was consistent with the phase I portion of the trial, in which the most common adverse events (≥ 30%, any grade) included nausea, decreased appetite, vomiting, alopecia, fatigue, anemia, diarrhea, and constipation. Cases of drug-related interstitial lung disease and pneumonitis, including grade 5 events, have also been reported in the clinical development program.
Fast Track Designation for Bemcentinib for Elderly Patients With Relapsed AML
The FDA granted Fast Track designation to bemcentinib for the treatment of elderly patients with AML whose disease has relapsed. There are currently no marketed drugs specifically approved for all patients with relapsed AML patients, representing a significant unmet medical need.
Many AML patients older than age 60 years are unable to tolerate intensive induction chemotherapy treatment.
Bemcentinib (formerly known as BGB324) is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development program. Ongoing clinical trials are investigating bemcentinib in multiple solid tumors and hematological malignancies, as monotherapy and in combination with current and emerging therapies (including immunotherapies, targeted therapies, and chemotherapy). Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumor cells, leading to aggressive metastatic cancers.
Breakthrough Device Designation for Novel Prostate Cancer Diagnostic Test
The FDA granted Breakthrough Device designation to the IsoPSA Assay, a novel prostate cancer diagnostic test. Published studies from multicenter prospective clinical trials suggest that the noninvasive, blood-based IsoPSA assay has significant superior diagnostic accuracy when compared to traditional prostate-specific antigen (PSA) tests in detecting high-grade prostate cancer.
Two multicenter clinical trials in U.S. and international hospitals and clinics led by the Cleveland Clinic compared the diagnostic accuracy of IsoPSA to that of PSA, the current standard of care in prostate cancer, in men scheduled for prostate biopsy. The results from those studies demonstrated that IsoPSA has superior diagnostic performance to traditional PSA in identifying which patients have high-grade disease.
The results of previous studies have shown that IsoPSA could reduce unnecessary biopsies by at least 45%, saving men from unneeded invasive, potentially risky, and expensive procedures that can sometimes lead to serious and lasting side effects.
FDA Statement on Continued Efforts to Enhance Safety Information Available to Patients Considering Breast Implants
The FDA is helping to ensure patients have complete information about the benefits and risks of breast implants. In a draft guidance issued, the Agency is providing proposed labeling recommendations to manufacturers of these devices to help ensure women receive and understand information regarding the benefits and risks of breast implants. The draft guidance offers numerous recommendations to help ensure women have access to this information, including that manufacturers incorporate a boxed warning and patient decision checklist in the device’s labeling, update recommendations for patient screening for device rupture, and more.
The FDA held a public advisory panel meeting earlier this year, and also gathered information from other ongoing efforts to engage with patients and stakeholders that there is a distinct opportunity to do more to protect women who are considering breast implants.
First, the FDA has proposed that a boxed warning be included in labeling for breast implants. A boxed warning generally will be noticeable and easy to read and understand. The boxed warning should help communicate risks that patients may not know. The FDA recommends that manufacturers identify certain risks in the boxed warning, including that breast implants are not lifetime devices; the chances of developing complications increase the longer a patient has the implant, and that additional surgery may be required to address the complications; and that breast implants have been associated with the risk of developing breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) and may be associated with systemic symptoms (like fatigue or joint pain). Calling out this information in a boxed warning will help ensure patients see this important information.
Additionally, the draft guidance recommended that manufacturers include a patient decision checklist at the end of a patient informational booklet or brochure, which can be used to help guide discussion during a patient’s consultation with a surgeon. A checklist gives patients the opportunity to acknowledge individual risks of breast implants, such as potential risks from the surgery, the risk of BIA-ALCL, and the risk of implant rupture, among others. An example of a checklist that incorporates these recommendations is provided in the draft guidance and encourages
Another recommendation described in the draft guidance focuses on revising the rupture screening recommendations for patients with silicone gel-filled breast implants. Previously, the FDA recommended that labeling include the method(s) and frequency of screening for rupture, and current approved labeling recommends magnetic resonance imaging (MRI) screenings for patients beginning 3 years following implantation and every other year thereafter. The new recommendations issued in draft today propose that patients without symptoms be screened using either ultrasound or MRI at 5 to 6 years following implantation and then every 2 years thereafter. If a patient has symptoms at any time or uncertain ultrasound results for breast implant rupture, an MRI is recommended. These new proposed screening recommendations are based on data showing rupture rates are higher 5 to 6 years after implantation; recommendations from the American College of Radiology; recommendations from the FDA panel meeting earlier this year; data suggesting that ultrasound is an effective screening method for asymptomatic patients; and the Agency’s awareness of poor patient compliance with the existing MRI recommendations. By proposing updates to the recommendations based on current science and other information, the FDA hopes to make it easier for patients to comply with these new recommendations.
The draft guidance also includes a recommendation that breast implant manufacturers include product ingredient information in the device’s labeling in a way that is easy for patients to understand, as the Agency first suggested in a statement released in May. Although this information is currently publicly available online in the FDA’s Summary of Safety and Effectiveness Data for each of the approved breast implants, the FDA is recommending that product ingredient information be included in the patient labeling in a format that is easy to understand to increase patient access to this information. The FDA believes that improved access to this descriptive information will help better inform patients of the types and quantities of chemicals and heavy metals that are in breast implants.
Finally, the draft guidance includes updates to previous recommendations concerning patient device cards. In 2006, the FDA recommended that manufacturers provide patients, following surgery, with a device card that includes information about style, size and serial number of the product. In the draft guidance, the FDA is proposing that manufacturers include more information on the device card, including the unique device identifier of the product; the boxed warning; and also provide web links to the patient decision checklist, boxed warning, and labeling for the specific implant so that patients may easily access any updated information on the manufacturer’s website.
After a period of public comment, once the guidance is finalized, manufacturers may choose to follow the recommendations in the final guidance or they may choose other methods of labeling their devices, so long as the labeling complies with applicable FDA laws and regulations.
The draft guidance is available for public comment. Information on how to submit comments is available in the Federal Register.
