A Look Back at February 2019 FDA News

In February 2019, the FDA announced several approvals for patients with gastric cancers, melanoma, and acquired thrombocytic thrombocytopenic purpura (aTTP). They also granted a number of priority review designations throughout the month. An orphan drug designation was granted, in addition to some other FDA news.

Here’s a look back on the FDA happenings for the month of February 2019:

Hematology Updates

Caplacizumab-yhdp Approved by FDA For Acquired Thrombotic Thrombocytopenic Purpura

The FDA approved the first treatment regimen for adult patients with aTTP on February 6, 2019. The nanobody caplacizumab-yhdp (Cablivi) was approved in combination with plasma exchange and immunosuppression.

Spero R. Cataland, MD, professor of internal medicine, Division of Hematology, Wexner Medical Center at Ohio State University, said this approval "provides new hope for adults in the US suffering with aTTP and provides a much-needed treatment option to help effectively manage aTTP episodes."

Split-Dosing of Daratumumab Approved by FDA for Multiple Myeloma

The FDA approved a split-dosing regimen of daratumumab (Darzalex), a CD28-directed monoclonal antibody, on February 12, 2019, for the treatment of patients with multiple myeloma. This approval gives physicians the option of splitting the first infusion of the agent over 2 consecutive days or completing the dose in 1 session.

This was approved based on results from the phase Ib EQUULEUS (MMY1001) trial. Findings showed the split-doing schedule was compared to single infusion with similar safety profiles.

FDA's ODAC Set to Review Selinexor Application in Penta-Refractory Myeloma

On February 7, 2019, the FDA announced they will hold a hearing on February 26, 2019, to discuss the new drug application for selinexor as treatment of patients with penta-refractory multiple myeloma. The manufacturer of this agent seeks an accelerated approval for the patients who have more than 3 prior lines of therapy.

UPDATE:FDA Panel Not in Support of Accelerated Approval of Selinexor in Myeloma

The FDA's Oncologic Drgus Advisory Committee (ODAC) voted against the accelerated approval of selinexor for the treatment of patients with penta-refractory multiple myeloma. The vote, announced on February 26, 2019, was 8 to 5. The ODAC has instead recommended delaying the decision on the new drug application until results are available from the pivotal phase III BOSTON trial.

Polatuzumab Vedotin Granted Priority Review Designation by FDA for DLBCL

Antibody-drug conjugate polatuzumab vedotin in combination with rituximab (Rituxan) and bendamustine was granted priority review by the FDA after demonstrating a 40% complete response rate in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This designation, granted on February 19, 2019, was based on the findings in the phase Ib/II GO29365 study (NCT02257567).

Ivosidenib Receives Priority Review From FDA for Frontline IDH1+ AML

On February 20, 2019, the FDA granted a priority review designation to ivosidenib (Tibsovo) for frontline treatment of patients withIDH1-mutant acute myeloid leukemia (AML) who are ineligible for standard chemotherapy.

Lenalidomide/Rituximab Receives Priority Review Designation From FDA for Indolent Non-Hodgkin Lymphoma

The FDA granted priority review to he R2 regimen of lenalidomide (Revlimid) plus rituximab (Rituxan) for the treatment of patients with previously treated follicular lymphoma and marginal zone lymphoma. The decision, announced February 26, 2019, was based on phase III data in the AUGMENT trial.

Gastrointestinal Cancer Updates

TAS-102 Receives FDA Approval for Gastric/GEJ Cancer

On February 25, 2019, the FDA approved TAS-102 (trifluridine/tipiracil; Lonsurf) for the treatment of adult patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

This approval was based on the results from the phase III TAGS trial; TAS-102 demonstrated a reduced risk of death by about one-third compared to placebo in patients with heavily pretreated gastric or GEJ cancer.

“If we look at the quality of life data that was presented in the original TAGS trial, there was a slowing of decline in performance status compared to placebo, so we do see a stabilization effect, and I think this drug will likely be an option for patients with refractory disease that don’t have other treatment options,” David H. Ilson, MD, PhD, attending physician and progresorh of medicine at Memorial Sloan Kettering Cancer Center,toldTargeted Oncologyahead of the approvalat the 2019 Gastrointestinal Cancers Symposium.

FDA Grants Etoposide Toniribate Orphan Drug Destination for Advanced Biliary Cancer

On February 25, 2019, the FDA granted an orphan drug designation to etoposide toniribate (EDO-S7.1) for the treatment of patients with relapsed/refractory biliary tract cancer.

This designation was granted based on findings from a phase II trial where 27 patients were randomized to either etoposide toniribate or best supportive care; a phase III study will be initiated in 2020 to further explore this agent in a larger cohort of patients.

Lung Cancer Updates

Entrectinib Granted Priority Review by FDA for NTRK+ Tumors and ROS1+ NSCLC

On February 19, 2019, the FDA granted a priority review designation to entrectinib as treatment of patients with NTRK fusion-positive locally advanced or metastatic solid tumors. This also includes patients with metastatic ROS1-positive non-small cell lung cancer.

Pembrolizumab Granted FDA’s Priority Review for Advanced SCLC

The FDA granted a priority review to pembrolizumab (Keytruda) for the treatment of patients with advanced small cell lung cancer whose disease has progressed following ≥2 prior lines of therapy on February 20, 2019.

Other FDA Updates

FDA Gives Avelumab/Axitinib Combination Priority Review Designation for RCC

On February 12, 2019, the FDA granted a priority review designation to the combination regimen of avelumab (Bavencio) and axitinib (Inlyta) for patients with advanced renal cell carcinoma (RCC), based on data from the pivotal phase III JAVELIN Renal 101 trial. Results showed the combination improved progression-free survival. In addition, this combination also double the objective response rates compared to sunitinib (Sutent) in treatment-naive patients.

Pembrolizumab/Axitinib Combo Receives Priority Review From FDA for Frontline RCC

Based on findings from the phase III KEYNOTE-426 trial, the combination pembrolizumab (Keytruda) and axitinib (Inlyta) received priority review on February 15, 2019, for the treatment of patients with advanced RCC.

In this trial, the combination significant improved progression-free survival and overall survival in the frontline compared to sunitinib (Sutent).

Pembrolizumab Approved by FDA for Stage III Melanoma

On February 19, 2019, the FDA granted approval to adjuvant pembrolizumab for the treatment of patients with high-risk stage III melanoma with lymph node involvement following complete resection.

In the pivotal phase III EORTC 1325/KEYNOTE-054 trial, this therapy led to a 43% reduction in the risk of disease recurrence or death versus placebo.

“Keytruda has demonstrated significant improvement in recurrence-free survival among stage III melanoma patients when compared to a placebo, and we now have a new option to help patients who have a high risk of recurrence,” said Alain Algazi, MD, associate clinical professor of medicine, Department of Medicine, Hematology/Oncology, University of California, San Francisco, Medical Center, in a press release.

Pexidartinib Granted Priority Review by FDA for Treatment of Tenosynovial Giant Cell Tumor

On February 5, 2019, the FDA granted a priority review to the investigational, small molecule, CSF1R receptor inhibitor pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor.

Review Period for Ruxolitinib in GVHD Extended by FDA

The FDA extended the review period for the SNDA for ruxolitinib (Jakafi) by 3 months on February 7, 2019. The JAK1/JAK2 inhibitors seeks approval as a treatment option for patients with acute graft-versus-host disease who have had an inadequate response to corticosteroids.

Pembrolizumab Receives Priority Reviews Designation from FDA for Frontline HNSCC

The FDA granted a priority review designation on February 11, 2019 to pembrolizumab either alone or in combination with 5-fluorouracil (5-FU) chemotherapy as a first-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma. Results from the phase III KEYNOTE-048 demonstrated an improvement in overall survival compared to standard chemotherapy.

Darolutamide Submitted for FDA Approval in Nonmetastatic CRPC

Based on findings from the phase III ARAMIS trial, a new drug application for darolutamide was submitted to the FDA on February 27, seeking the investigational agent's approval as a treatment for patients with nonmetastatic castration-resistant prostate cancer, according to the codevelopers of the investigational agent, Bayer and Orion Corporation.

Subcutaneous Trastuzumab Formulation Receives FDA Approval for HER2+ Breast Cancer

Subcutaneous use of trastuzumab (Herceptin) and hyaluronidase-oysk injection (Herceptin Hylecta) was approved by the FDA on February 28 in combination with chemotherapy for the treatment of select patients with HER2-positive early breast cancer, in combination with paclitaxel in patients with metastatic HER2-positive breast cancer as a frontline treatment, and alone for patients with metastatic disease who have received at least 1 prior chemotherapy regimen.

Aprepitant Injection Receives for FDA Approval for CINV