FDA Grants Multi-Epitope Vaccine Orphan Designation for Ovarian Cancer

An orphan drug designation has been granted to the multi-epitope folate receptor alpha (FRα) vaccine TPIV 200 as a treatment for patients with ovarian cancer by the FDA.

Patrick Yeramian, MD

An orphan drug designation has been granted to the multi-epitope folate receptor alpha (FRα) vaccine TPIV 200 as a treatment for patients with ovarian cancer by the FDA.

According to a statement from the drug's developer, TapImmune, the designation was based on findings from a phase I study, which were electronically published in conjunction with the 2015 ASCO Annual Meeting.

"Ovarian cancer is highly aggressive, clinically evasive, and, with current treatment modalities, time to recurrence is relatively short and prognosis upon recurrence is poor," Patrick Yeramian, MD, vice president and chief medical officer at TapImmune, said in a statement. "The FDA's decision to grant TPIV 200 orphan designation underscores the need for additional therapeutic options and validates the scientific rationale of TapImmune's approach."

Treatment with the vaccine was associated with FRα-specific T-cell response that persisted beyond the completion of the study for a majority of patients. In total, FRα is expressed on nearly 90% of ovarian cancer cells.

In the phase I study, 22 patients with breast or ovarian cancer were enrolled following surgery and adjuvant therapy. Prior to receiving the vaccine, patients were treated with 1 cycle of cyclophosphamide on days 1 to 7 and 15 to 22, to reduce immunosuppressive T regulatory cells (Tregs). The vaccine, which contained the 5 peptides FR30, FR56, FR76, FR113, and FR238, was administered intradermally at three sites on the first day of each subsequent cycle following cyclophosphamide for a maximum of 6 cycles.

The safety of the vaccine was assessed at each visit. Peripheral blood samples were collected for immune monitoring at baseline, each cycle, and after 3, 6, and 12 months. Immune response was assessed using flow cytometry for the number of Tregs. Enzyme-Linked ImmunoSpot was used to assess the number of antigen-specific T cells.

Overall, the median number of Tregs was not impacted by pretreatment with cyclophosphamide, suggesting the need for a better lymphodepletion regimen. An initial immune response was observed in 95% of evaluable patients treated with TPIV 200 (n = 20). A majority of these responses (80%) persisted beyond 3 months and continued during a subsequent observation phase.

Adverse events were experienced by 64% of patients enrolled in the trial, including one grade 3 injection site reaction. Overall, the most common adverse events (all grade 2) were lymphopenia (23%), neutropenia (18%), injection site reactions (9%), and leukopenia (9%).

“These immune response data provide a strong rationale for progression into phase II trials. We have assembled an experienced team of advisors and experts to assist us in moving the next trial forward as quickly as possible,” Glynn Wilson, PhD, chairman and CEO of TapImmune, said in a statement.

The orphan drug designation is granted to treatments for rare diseases or conditions. The orphan designation provides tax credits for clinical trials and a waiver of the prescription drug user fee. Outside of these items, the designation does not change the standard regulatory requirements for marketing applications.

The TPIV 200 vaccine is being developed through a close collaboration with Mayo Clinic. In addition to ovarian cancer, the agent has shown promise for patients with breast cancer. In September 2015, Mayo Clinic received a $13.3 million grant to explore the vaccine in a phase II trial for patients with triple-negative breast cancer. This study is expected to enroll 280 patients.

“Manufacturing of peptides for phase II trials is already underway and final analysis of clinical plans and clinical sites for the treatment of triple-negative breast cancer is nearing completion for the start of phase II studies later in 2015," Wilson noted.