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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.

Wednesday, July 27, 2016

The FDA granted the premarket approval application (PMA) for the new Photofrin 630 PDT Laser.

Photodynamic therapy (PDT) with Photofrin is a light-based cancer treatment that combines a photosensitizing drug called Photofrin (porfimer sodium) with a specific type of light administered

by a laser to attack cancer cells.

The newly approved laser, which is designed for use with Photofrin to treat esophageal cancer, Barrett's Esophagus, and non-small cell lung cancer, has been re-engineered with technological advancements in laser design. These advancements include new controls and peripheral systems while maintaining the same specifications with minimal changes to the treatment procedures.

Photofrin is also being evaluated as a rare disease product candidate through a phase III clinical trial. The ongoing trial is evaluating the product's safety and efficacy as a potential treatment for cholangiocarcinoma, or bile duct cancer, which is a rare disease affecting approximately 2,000-3,000 patients annually in the U.S.​

Wednesday, July 27, 2016

Seribantumab (MM-121) has received Fast Track designation from the FDA for development in patients with heregulin-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed following immunotherapy.

Fast Track is a program designed by the FDA to facilitate and expedite the development and review of drugs that treat serious conditions and fill an unmet medical need. The SHERLOC trial,

a global clinical study of seribantumab in combination with docetaxel or pemetrexed in heregulin-positive patients with NSCLC, is being conducted and designed to support a Biologics License Application to the FDA. Seribantumab is a fully human monoclonal antibody that targets ErbB3.

Heregulin-positive disease has been linked to rapid progression and poor prognosis in multiple types of cancer, including NSCLC. The higher the prevalence of heregulin-positive cancer cells in a tumor, the lower the anti-tumor effect of the chemotherapy. Seribantumab is designed to block heregulin-driven signaling and enhance the anti-tumor effect of the chemotherapy.

Data from prior clinical studies have shown standard-of-care therapy may be more effective and result in improved patient outcomes when combined with seribantumab. The efficacy and safety of seribantumab plus standard-of-care therapy is being investigated in the SHERLOC trial.​

Wednesday, July 27, 2016

The FDA has granted accelerated approval to Opdivo (nivolumab) for the treatment of patients with

classical Hodgkin lymphoma (cHL) who have relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (Adcetris).

The approval was based on two single arm, multicenter trials of nivolumab in adults with relapsed or refractory cHL. The trials enrolled patients regardless of PD-L1 expression status on Reed-

Sternberg cells. The primary efficacy endpoint was objective response rate (ORR) as determined by an independent radiographic review committee. Additional outcome measures included duration of

response (DOR).

Efficacy was evaluated in 95 patients previously treated with autologous HSCT and post-transplantation brentuximab vedotin. Patients had a median of five prior systemic regimens (range: 3,

15) and received a median of 17 doses of nivolumab (range: 3, 48). Single-agent nivolumab produced a 65 percent ORR (95% CI: 55%, 75%), with 58 percent partial remission and 7 percent complete remission. The median time-to-response was 2.1 months (range: 0.7 to 5.7 months). The estimated median DOR was 8.7 months.

Safety was evaluated in 263 patients with relapsed or refractory cHL. Ninety-eight percent of patients had received autologous HSCT. Patients received a median of 10 doses of nivolumab (range:

1, 48) at the approved dose-schedule. The most common (reported in at least 20%) adverse reactions of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea. Additional common adverse reactions (reported in at least 10%) included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.

Other immune-mediated adverse reactions, occurring in 1-5 percent of patients included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. Serious adverse reactions were reported in 21 percent of patients. The most common SAEs, reported in 1-3 percent of patients were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

A new "Warning and Precaution" was issued for complications of allogeneic HSCT after nivolumab. Transplant related deaths have occurred, and health care professionals should follow patients closely for early evidence of transplant-related complications, such as hyper-acute

graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno- occlusive disease, and other immune-mediated adverse reactions. The FDA has required the

manufacturer to further study the safety of allogeneic HSCT after nivolumab.

The recommended dose schedule of nivolumab is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. Continued approval for the cHL indication may be contingent upon verification of clinical benefit through a randomized phase III trial.​

Friday, July 8, 2016

Napabucasin has been granted Orphan Drug Designation from the FDA in the treatment of gastric cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin is an orally administered cancer stemness inhibitor designed to inhibit cancer stemness pathways by targeting STAT3, and is currently being investigated in a global Phase III clinical trial in combination with paclitaxel in patients with advanced gastric and GEJ cancer (the BRIGHTER study).

The FDA's Orphan Drug Designation program provides special status and development incentives for drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S. Each year, about 26,000 people in the U.S. are diagnosed with gastric cancer.

Phase Ib/II data for napabucasin in gastric/GEJ cancer were previously presented at the American Society of Clinical Oncology 2015 Annual Meeting; these data found that napabucasin and weekly paclitaxel can be combined in patients with advanced pre-treated gastric/GEJ cancer. Lesion regression, objective responses and prolonged stable disease were observed in heavily pre-treated patients. Common adverse events identified through this clinical trial included grade 1 or 2 diarrhea, nausea, fatigue, abdominal pain, vomiting and anorexia.

Friday, July 8, 2016

The FDA has granted a fourth breakthrough therapy designation (BTD) for ibrutinib (Imbruvica) as monotherapy for the treatment of patients with chronic graft-versus-host-disease (cGVHD) after failure of one or more lines of systemic therapy.

The FDA also granted the therapy orphan drug designation (ODD) for cGVHD. This marks the first time ibrutinib has been granted BTD or ODD for an indication beyond hematologic malignancies. In current clinical practice, there are no approved treatments or established standards of care specifically indicated for patients with active cGVHD who have failed first-line corticosteroid therapy and require additional therapy.

GVHD is a life-threatening condition in which the body is attacked by donor immune cells after a patient undergoes an allogeneic stem cell or bone marrow transplant. Currently, most GVHD patients are prescribed glucocorticoids, a type of steroid treatment, but many do not respond.

The FDA granted ibrutinib BTD for cGVHD based on data from a phase Ib/II study. Overall, ibrutinib showed early clinical activity in the reduction of cGVHD based on the National Institutes of Health (NIH) Consensus Response Criteria. Preliminary results from this trial were previously presented at the Annual Meeting of the European Society for Blood and Marrow Transplantation in April and the American Society of Clinical Oncology Annual Meeting in May 2015.

According to the FDA, BTD is intended to expedite the development and review of treatments for serious or life-threatening diseases where "preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development." ODD provides special status to a therapy developed to treat a rare condition or disease.

In February 2013, the FDA granted BTD to Imbruvica for the treatment of patients with relapsed or refractory mantle cell lymphoma and for the treatment of patients with Waldenström's macroglobulinemia. In April 2013, Imbruvica was awarded a third BTD for the treatment of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma with a deletion of the short arm of chromosome 17 (del 17p).

About the Author

Sarah DiGiulio