On December 16, 2014, the U. S. Food and Drug Administration approved lanreotide (Somatuline Depot Injection, Ipsen Pharma) for the treatment of patients with unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival (External Source US FDA, Ipsen, DEC 16, 2014, View Source [SID:1234501196]). Lanreotide was previously approved for the long-term treatment of acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option.

The approval was based on demonstration of improved progression-free survival (PFS) in a multi-center, international, randomized (1:1), double-blind, placebo-controlled study (Trial 2- 55-52030-726) that enrolled 204 patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic, non-functioning GEP-NETs. Fifty-five percent of patients (113/204) had neuroendocrine tumors arising outside the pancreas. Patients were randomized to receive either lanreotide 120 mg or placebo subcutaneously every 28 days.

The primary efficacy endpoint was PFS as determined by independent radiology review. The trial demonstrated a significant prolongation of PFS for the lanreotide arm [HR 0.47 (95% CI: 0.30, 0.73); p < 0.001; log-rank test]. The median PFS in the lanreotide arm had not been reached at the time of the final analysis and will exceed 22 months. The median PFS in the placebo arm was 16.6 months. Safety data were evaluated in 101 patients who received at least one dose of lanreotide. The most commonly (greater than or equal to 10%) reported adverse reactions in lanreotide-treated patients were abdominal pain, musculoskeletal pain, vomiting, headache, injection site reaction, hyperglycemia, hypertension, and cholelithiasis. The most common serious adverse reaction of lanreotide observed in this trial was vomiting (4%). The recommended dose and schedule for lanreotide for GEP-NET is lanreotide 120 mg administered by deep subcutaneous injection every 28 days. Treatment should continue until disease progression or unacceptable toxicity. Full prescribing information is available at: View Source

On December 16, 2014 Novartis reported that the US Food and Drug Administration (FDA) has approved Signifor long-acting release (LAR)* (pasireotide) for injectable suspension, for intramuscular use, for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option (Press release Novartis, DEC 15, 2014, View Source [SID:1234501194]). The approval of Signifor LAR, a next-generation somatostatin analog (SSA), helps address a critical unmet need among the acromegaly patient population. Signifor LAR has been studied and found effective in both medically naïve patients with acromegaly who have had prior surgery or for whom surgery was not an option, as well as patients whose disease is not fully controlled on first generation SSAs[2].

Acromegaly is a rare, debilitating endocrine disorder caused by the excess production of growth hormone (GH) and insulin-like growth factor-1 (IGF-1)[1],[3]. In the majority of cases, the disease is caused by a non-cancerous tumor on the pituitary gland. Prolonged exposure to GH and IGF-1 may cause patients to experience extreme physical changes including the enlargement of hands, feet and facial features[1]. Acromegaly is also associated with two- to three-fold increased mortality rates and serious health complications, including heart disease, hypertension, diabetes, arthritis and colon cancer[1],[4],[5]. In fact, heart disease is responsible for approximately 60% of deaths among people with acromegaly[6].

“Treating acromegaly can be extremely challenging and the consequences of inadequate normalization of hormone levels can be serious for patients,” said Dr. Monica Gadelha, Professor, Federal University of Rio de Janeiro and pivotal trial study author. “With the approval of Signifor LAR, physicians now have a new acromegaly therapy that provides an enhanced mechanism to address elevated hormone levels. This is a significant achievement and much welcomed news for patients with acromegaly.”

Worldwide, the prevalence of acromegaly is estimated to be 60 cases per million, with an annual incidence of 3 to 4 new cases per million[1]. However, recent studies suggest that pituitary adenomas may be more prevalent than previously thought, and that the prevalence of acromegaly may be between 115 and 295 cases per million[3]. On average, patients experience a delayed diagnosis of 6 to 10 years from disease onset[7]. Once diagnosed, the primary objective when treating acromegaly is to achieve biochemical control of the disease, as measured by both the reduction of GH levels and normalization of IGF-1 levels[8]. Notably, a recent meta-analysis using more sensitive assays and more stringent evaluation criteria showed that 45% of patients with acromegaly fail to achieve recommended levels of GH or normalized levels of IGF-1[9]. Reduction of tumor volume and minimization of clinical manifestations are other important treatment goals[8].

This FDA approval was based on two multicenter Phase III studies, C2305 and C2402, which respectively examined medically naïve patients who have had prior surgery or for whom surgery was not an option and patients with acromegaly inadequately controlled on first generation SSAs. In both studies, higher rates of full biochemical control (defined as mean GH level <2.5mcg/L and normal IGF-1 levels) were achieved with Signifor LAR compared to a first generation SSA[2]. "The FDA approval of Signifor LAR for acromegaly marks an important day for physicians and patients living with difficult-to-treat pituitary conditions and underscores our continued commitment to helping patients manage rare diseases," said Bruno Strigini, President, Novartis Oncology. "We are pleased that a new treatment option is now available to help address the serious impact of uncontrolled acromegaly, and are optimistic about providing this much needed treatment to other patients worldwide in the near future." Signifor LAR is an SSA administered intramuscularly once-monthly that exerts its pharmacological activity via binding to somatostatin receptors (SSTRs). Signifor LAR has the potential to stimulate both SSTR2 and SSTR5 subtype receptors, which are relevant for inhibition of GH and IGF-1 secretion, making Signifor LAR a more effective treatment for acromegaly compared to other SSAs currently used to treat this disease[2]. In the US, Signifor LAR has orphan drug designation for acromegaly. Orphan drug designation is granted for products that treat a condition that affects fewer than 200,000 people in the US[10],[11]. In November 2014, the European Medicines Agency (EMA) approved Signifor* to treat adult patients with acromegaly for whom surgery is not an option or has not been curative and who are inadequately controlled on treatment with a first-generation SSA. Novartis has also submitted additional regulatory applications for Signifor LAR worldwide.

On December 15, 2014 Sorrento Therapeutics reported that it has entered into a binding agreement with NantWorks founder, physician scientist, and biotechnology entrepreneur Dr. Patrick Soon-Shiong (Filing 8-K , Sorrento Therapeutics, DEC 15, 2014, View Source [SID:1234501189]).

Under the terms of the agreement, NantWorks and Sorrento will establish a global strategic collaboration to jointly develop next generation immunotherapies for the treatment of cancer and auto-immune diseases. NantWorks, through a subsidiary, and Sorrento intend to establish the first joint venture – “The Immunotherapy Antibody JV” – as an independent biotechnology company with $20 million initial joint funding. As part of a strategic investment, Dr. Soon-Shiong’s affiliated entity will acquire a 19.9% equity stake in Sorrento by purchasing common stock priced at $5.80 per share, Sorrento’s closing sale price on Friday, December 12, 2014. In addition, Sorrento granted the purchaser a 3-year warrant to purchase 1,724,138 shares of common stock at an exercise price of $5.80 per share.

The Immunotherapy Antibody JV will focus on accelerating the development of multiple immuno-oncology monoclonal antibodies (mAbs) for the treatment of cancer, including but not limited to anti-PD-1, anti-PD-L1, anti-CTLA4 mAbs, and other immune-check point antibodies as well as antibody drug conjugates (ADCs) and bispecific antibodies. The immuno-oncology field has emerged as the one of most exciting and fastest developing pharmaceutical market. Immunomodulatory antibodies help the cancer patient’s own immune system to fight the disease and are being developed for the treatment of a number of solid tumors. They have demonstrated therapeutic potential in difficult-to-treat cancers, such as metastatic melanoma and non-small cell lung cancer (NSCLC). A recent forecast by Citigroup predicts this market to become the biggest blockbuster drug class in history with potential sales of up to $35 billion a year over the next 10 years.

“We are extremely pleased to be working with Dr. Patrick-Soon Shiong and NantWorks. The investment into Sorrento and future formation of the JV with NantWorks further validate our G-MAB antibody technology and underscore Sorrento’s commitment to seeking strategic alliances in bringing its diverse portfolio of fully human monoclonal antibodies, ADCs, and bispecific antibodies into the clinic,” said Dr. Henry Ji, President and CEO of Sorrento. “Our innovative collaboration will unite Sorrento’s capability to develop complex biologics with NantWorks proprietary genomic and personalized medicine technologies. We share NantWorks’ enthusiasm for the potential of our JV to produce a pipeline of immuno-oncology products to address unmet needs of cancer treatment.”

“Combining NantWorks’ cutting edge expertise in genomic and molecular profiling of cancer patients and Sorrento’s industry-leading G-MAB antibody technology, we believe will enable us to develop multiple novel therapies for malignant disorders where there is currently a significant unmet need. Through this partnership, it is our goal to provide relief for millions of people who today have limited treatment options. This will be a model relationship aligned to accelerate development and production of novel cancer immunotherapies. We look forward to working closely with Sorrento’s team,” said Dr. Patrick Soon-Shiong, CEO and Founder of NantWorks.