On February 20, 2015 Pfizer reported that the U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental New Drug Application (sNDA)for RAPAMUNE (sirolimus) for the treatment of lymphangioleiomyomatosis (LAM), a rare, progressive lung disease in women of childbearing age that is often fatal (Press release Pfizer, FEB 20, 2015, View Source [SID:1234501822]). With the Priority Review designation for the sNDA, we anticipate a decision in June of 2015 based on the anticipated Prescription Drug User Fee Act (PDUFA) action date.

“If approved, RAPAMUNE would be the first FDA approved treatment option for patients living with LAM,” said Steve Romano, MD, SVP and head of Global Medicines Development at Pfizer’s Global Innovative Pharmaceuticals Business. “We look forward to continuing to work closely with the FDA throughout the review process.”

The sNDA is based on results from the Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) Trial. The MILES Trial included 89 LAM patients with moderate lung impairment who were randomized to receive RAPAMUNE (dose adjusted to 5-15 ng/mL) or placebo for 12 months, followed by a 12 month observation period. In the trial, those treated with RAPAMUNE for one year experienced stabilization of lung function as measured by forced expiratory volume in one second (FEV1). Full results of the MILES Trial were published in the New England Journal of Medicine. The most common adverse events reported during the study were mucositis, diarrhea, nausea, hypercholesterolemia, acneiform rash and swelling in the lower extremities. The adverse drug reactions observed were consistent with the known safety profile of RAPAMUNE in renal transplant patients, with the exception of weight decreased, which was reported at a greater incidence with RAPAMUNE compared to placebo.

“The results of the MILES Trial demonstrated that RAPAMUNE has the potential to stabilize lung decline in patients suffering from LAM,” said Dr. Francis X. McCormack, Director of Pulmonary, Critical Care and Sleep Medicine at the University Of Cincinnati School of Medicine and the lead investigator of the MILES Trial. “We are excited about the FDA’s review of RAPAMUNE and the potential to make this medication available to LAM patients.”

The MILES trial was conducted by Dr. McCormack and conducted within the NIH Rare Lung Diseases Consortium. Pfizer provided study drug and a portion of the funding but had no involvement in the design or conduct of the study. The LAM Foundation assisted with the recruitment of patients and logistics for the study.

“For 20 years, the LAM Foundation has been committed to seeking treatment options for LAM and we are thrilled about the possibility of getting a therapy approved to treat this rare and potentially deadly disease,” said Susan E. Sherman, Executive Director of the LAM Foundation.

On February 20, 2015 Celsion Corporation reported clinical and preclinical data demonstrating the safety, biological activity and clinical benefits of GEN-1, its DNA-based immunotherapy, as a single agent in advanced platinum-resistant and recurrent ovarian cancer patients, at the Molecular Medicine TRI-Conference in San Francisco (Press release Celsion, FEB 20, 2015, View Source [SID:1234501821]). These data provide support for advancing GEN-1 into clinical development in the front-line setting. The Company also announced that the U.S. Food and Drug Administration (FDA) has accepted, without comment, its planned Phase 1 dose-escalation clinical trial of GEN-1 in combination with the standard of care in neo-adjuvant ovarian cancer, which is expected to commence in mid-2015 at five to six U.S. clinical centers.

“These important findings significantly strengthen our established clinical and preclinical data providing additional evidence of GEN-1’s ability to effectively recruit a cellular immune system response, widely known for its anti-cancer activity. Evidence now in platinum-resistant and recurrent ovarian cancer patients, populations which historically have had little to no response to new investigational therapies, is highly encouraging,” stated Khursheed Anwer, Ph.D., Executive Vice President and Chief Scientific Officer of Celsion. “Based on the level of activity observed in these advanced patient populations, we believe that GEN-1 has the potential to produce a robust response in the neo-adjuvant setting, where patients typically have healthier immune systems and no prior treatment with immunosuppressive drugs.”

Today’s presentation at the Molecular Medicine TRI-Conference included data from the recently completed Phase 1b dose-escalation combination study of GEN-1, as well as a review of previously reported data. The Phase 1b study enrolled 16 patients with platinum-resistant ovarian cancer and evaluated the safety, tolerability and efficacy of GEN-1 in combination with pegylated doxorubicin. Patients received pegylated liposomal doxorubicin on day 1 and GEN-1 intra-peritoneally (IP) over days 1, 8, 15 and 22. This treatment course was repeated every 28 days in the absence of disease progression or unacceptable toxicity. The findings demonstrated that there were no overlapping toxicities between GEN-1 and pegylated doxorubicin. Biological activity and clinical efficacy results from this Phase 1b study including disease control rates, translational data and survival rates among the three doses evaluated have been submitted for presentation at the American Society of Clinical Oncologist (ASCO) (Free ASCO Whitepaper) Conference in the second quarter of 2015 and will be publicly available following ASCO (Free ASCO Whitepaper)’s normal publication schedule. Patients will be followed quarterly for up to one year following completion of study treatment.

The data from the Phase 1b study was consistent with previously reported data from two single-agent studies of GEN-1 in platinum-resistant recurrent ovarian cancer. In an earlier Phase 1 study, treatment with GEN-1 demonstrated a DCR of 31%, biological activity and median overall survival (OS) of 18 months. In the Phase 2 study, treatment with GEN-1 demonstrated a DCR of 45% and a median OS of 10 months. In both studies, GEN-1 was well tolerated and no maximum tolerated dose (MTD) was achieved.

“The data presented today highlights the potential value and promise of our IL-12 immunotherapy program and our expectations for the TheraPlas platform generally,” said Michael H. Tardugno, Celsion’s Chairman, President and Chief Executive Officer. With results that pave the way for GEN-1 to provide a promising new approach for treating ovarian cancer, we are now focused on launching our upcoming combination trial, which is designed to help identify a maximum tolerated dose of GEN-1 and will inform the design of our planned Phase 2 study in the front line setting, where new therapies are desperately needed. We will collect translational data to better understand the relationship between higher doses of GEN-1 and the effect on stimulation of the patients’ immune system.”

The combination trial is designed to enroll three to six patients per dose level until a safe, tolerable and potentially therapeutically active dose is identified. The study will evaluate safety and efficacy and attempt to define an optimal dose to carry forward into a Phase 2 trial.