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.

On February 20, 2015 Celgene International Sàrl reported that the European Commission (EC) has approved REVLIMID (lenalidomide) for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant (Press release Celgene, FEB 20, 2015, View Source [SID:1234501816]).

The REVLIMID Marketing Authorisation has been updated to include this new indication in multiple myeloma, building upon the already approved indication of REVLIMID in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least one prior therapy.

Multiple myeloma is a persistent and life-threatening blood cancer that is characterised by tumour proliferation and suppression of the immune system. It is a rare but deadly disease: around 38,900 people were newly diagnosed with multiple myeloma in Europe in 2012, and 24,300 people died from the disease in the same year. On average, multiple myeloma is diagnosed in people 65-74 years of age, and the majority of newly diagnosed patients may not be eligible for more aggressive treatment options such as high-dose chemotherapy with stem cell transplant.

Professor Thierry Facon, Services des Maladies du Sang, Hôpital Claude Huriez, and CHRU Lille, France, says: “Having a new treatment option now available for patients newly diagnosed with multiple myeloma is a real step forward. Treating patients continuously until disease progression is supported by several clinical studies, and will have an important impact on how we manage the disease over the long-term.”

“We are very pleased that physicians can now offer their patients a new and different treatment option,” said Tuomo Pätsi, President of Celgene in Europe, the Middle East and Africa (EMEA). “Multiple myeloma is rare, but it is devastating for those who have it, and it has a major impact on their friends and family too. We have seen significant progress in the treatment of the disease over the years, with an improvement of more than 50% in 5-year survival rates, but there continues to be a need for innovative new approaches to turn deadly diseases, like this one, into manageable, long-term, chronic conditions.”

The EC decision in newly diagnosed multiple myeloma was based on the results of two pivotal studies: MM-020 (also known as the FIRST trial) and MM-015.

The FIRST study, MM-020, was one of the largest phase III, multi-centre, open-label, randomised studies in patients newly diagnosed with multiple myeloma and not eligible for stem cell transplantation, including 1,623 patients. It compared lenalidomide plus dexamethasone administered in 28-day cycles until disease progression (Rd), with Rd for 72 weeks (18 cycles; Rd18) and melphalan-prednisone-thalidomide (MPT) for 72 weeks. Progression-free survival (PFS; study primary endpoint) was significantly improved in patients treated continuously with Rd, compared with those receiving MPT (primary comparison, p < 0.0001) or Rd18 (p < 0.0001). Median overall survival (OS) in patients receiving Rd continuous therapy was 58.9 months, vs. 48.5 months for patients treated with MPT (HR 0.75; 95% CI 0.62, 0.90), based on a March 3, 2014 interim OS analysis. The numbers of patients experiencing any grade 3 or 4 adverse event were similar in each group. The most frequent grade 3 or 4 adverse events were neutropenia, anaemia and infections. MM-015 was a multi-centre, randomised, double-blind, placebo-controlled phase III study of 459 patients that compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients ≥65 years or older with newly diagnosed multiple myeloma. Progression-free survival (PFS; study primary endpoint) was significantly improved in patients treated with MPR-R when compared with MPR and MP (p < 0.001 for comparisons of MPR-R over MPR and MP). In the MM-015 study, overall survival was not significantly improved when compared across any treatment arm. During induction, the most frequent adverse events were hematologic (including neutropenia, thrombocytopenia, and anaemia). During the maintenance phase, the incidence of new or worsened grade 3 or 4 adverse events was low (0 to 6%). The EC decision for the use of REVLIMID in newly diagnosed multiple myeloma in adult patients ineligible for transplantation follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) in December 2014. It is the second European Commission approval Celgene has received this year, following the approval of OTEZLA, the first phosphodiesterase-4 (PDE-4) inhibitor for use in psoriasis and psoriatic arthritis, in January 2015. A CHMP positive opinion was also issued in January for use of the company's oncology drug ABRAXANE, in non-small cell lung cancer. Celgene announced on 18 February 2015 that the U.S. Food and Drug Administration (FDA) has expanded the existing indication for REVLIMID (lenalidomide) in combination with dexamethasone to include patients newly diagnosed with multiple myeloma in the U.S.