Foster Analytical Services Speed Time to Market for Drug Delivery Formulations

Foster Delivery Science, a business unit for Foster Corporation, recently announced it has added comprehensive in-house laboratory services to expedite the screening of early stage formulations, process development, and post-extrusion studies of solid dose drug delivery forms using hot-melt extrusion. As a contract research and manufacturing company that specializes in hot-melt extrusion, Foster Delivery Science analytical services includes thermal analysis, spectroscopy, and chromatography equipment specifically designed for solid oral doses produced from this processing method.

Foster’s new thermogravimetric analysis (TGA), differential scanning calorimeter (DSC), and Fourier Transform infrared spectroscopy (FTIR) equipment allow for screening of drug-polymer combinations with suitable mixing characteristics. These tests are also used to characterize crystalline and amorphous solids and in the melt-extruded drug-polymer matrix. High-performance liquid chromatography equipment (HPLC) provides quantitation of the drug and its related substances in the melt-extruded formulations and in dissolution studies, a critical characteristic when attempting to enhance the solubility of a poorly soluble drug molecule.

Foster Delivery Science is a unique pharmaceutical contract organization with a sole focus on hot-melt extrusion for drug delivery. With the addition of analytical services, the company is able to provide rapid screening of drug-polymer candidates suitable for hot-melt extrusion, and leverage this information to establish extrusion conditions for initial trials. Samples can be evaluated immediately after initial trials to confirm an amorphous solid solution or dispersion formation and monitor recrystallization of the drug in the matrix. This closed-loop approach greatly enhances evaluation and development time of dosage forms using hot-melt extrusion.

“We have over 2 decades of hot-melt extrusion experience in healthcare applications, and in the pharmaceutical industry, there are really no other contract service providers that focus only on this process for solid dose drug delivery. The addition of in-house characterization services allows us to accelerate time to market for our customers with rapid data-based decision-making throughout the development cycle,” said Tony Listro, Managing Director at Foster Delivery Science. “This is part of a bigger initiative to continue to provide leadership as a pharmaceutical contract organization specializing in hot melt extrusion.”

OctoPlus Enters Development & Manufacturing Agreement With Ferring Pharmaceuticals

OctoPlus N.V. recently announced a formulation development and manufacturing contract has been signed with Ferring Pharmaceuticals A/S, a leading innovative pharmaceutical company. The undisclosed contract value will make a material contribution to OctoPlus’ 2012 revenues. Further details on the compound and activities are not disclosed.

OctoPlus is a specialty pharmaceutical company focused on the development and manufacture of improved injectable pharmaceuticals based on its proprietary drug delivery technologies that exhibit fewer side effects, improved patient convenience, and a better efficacy/safety balance than existing therapies. OctoPlus also focuses on the development of long-acting, controlled-release versions of known protein therapeutics, peptides, and small molecules, including specialty generics.

The clinically most advanced product incorporating its technology is Locteron, a controlled-release formulation of interferon alpha for the treatment of chronic hepatitis C. OctoPlus licensed Locteron exclusively to Biolex in October 2008. Locteron is being manufactured for Biolex by OctoPlus and has recently completed Phase IIb clinical studies with superior clinical data versus current treatment.

In addition, OctoPlus is a leading European provider of advanced drug formulation and clinical-scale manufacturing services to the pharmaceutical and biotechnology industries, with a focus on difficult-to-formulate active pharmaceutical ingredients.

Celerion First Early-Stage CRO to Adopt Participant Verification System

Celerion recently announced it has implemented VCT Verify from Verified Clinical Trials, to instantaneously ensure accurate participant identification and qualification for clinical research. Celerion is the first Early Stage Contract Research Organization (CRO) to partner with Verified Clinical Trials to set the standard for the industry to adopt.

Celerion will more effectively screen and select higher quality study participants by using this tool to instantly identify ineligible candidates for enrollment. The system searches a global clinical database registry to identify participants that are currently enrolled in other clinical studies. Clients benefit from improved participant selection and higher data integrity.

Celerion chose to implement the VCT Verify product across all its global clinical facilities to solve the long-recognized problem of inaccurate applications that compromise study success. The system has been reviewed and applauded by numerous Institutional Review Boards (IRBs), and Verified Clinical Trials is safe harbor certified.

“Celerion continues to apply rigorous standards to protect the safety of participants and enhance data integrity while supporting our commitment to our clients. This implementation sets a standard in the industry to continue to improve clinical research and more effectively bring new drugs to the market,” said Phil Bach, Vice President of Global Clinical Research at Celerion. “We are excited to partner with Verified Clinical Trials, the leader in this specialized field, to take a firm stance on ensuring the highest quality data and participants for our clients.”

“Verified Clinical Trials offers a comprehensive and unique clinical research database registry to enhance the quality of both early and late-stage studies globally. The system has been designed to streamline the clinical trial process and offers protection from various other potential liabilities,” added Mitchell Efros, MD FACS, CEO at Verified Clinical Trials. “We are pleased to be working with Celerion, the first CRO to implement this product, as they continue to demonstrate their leadership position in the industry.”

Celerion is the premier provider of innovative early-stage clinical research solutions. From facilities strategically located around the world, advanced scientific and technological expertise is applied to global clinical research (over 730 beds in Phases 0, I and IIa, NDA-enabling clinical pharmacology, ADME), clinical pharmacology sciences, global bioanalytical services (discovery through late stage), and drug development services.

Verified Clinical Trials is a forward-thinking company developed by experts active in the clinical research community to proactively improve research subject safety and data quality in clinical research trials. Verified Clinical Trials defines itself as the world’s leader in the field of database registries in clinical trial research and is the only clinical research database registry designed specifically to enhance the quality of both early and late phase trials and has the scalability to reach all sites nationally as well as on a global level.

Alize Pharma Licenses ASPAREC Therapy for ALL to EUSA Pharma

Alize Pharma II, recently announced the signing of a licensing agreement with EUSA Pharma for ASPAREC, a new L-asparaginase product currently in Phase I clinical development for the treatment of acute lymphoblastic leukemia (ALL).

Pursuant to the agreement, EUSA Pharma will be responsible for the development and worldwide commercialization of ASPAREC. In return, Alize Pharma has received an up-front payment and will be entitled to additional regulatory milestone payments and royalties on sales. The companies have not disclosed further financial information.

ASPAREC is Alize Pharma’s PEGylated recombinant L-asparaginase derived from Erwinia chrysanthemi. It is being developed as a treatment for ALL in patients with hypersensitivity to E. coli-derived L-asparaginase. Preclinical data indicate that ASPAREC is both longer acting and less immunogenic than the currently available Erwinia chrysanthemi-derived L-asparaginase product.

“This agreement between Alize Pharma and EUSA Pharma, a worldwide leader in the development and marketing of L-asparaginase products, is excellent news for us, for our investors, and for ALL patients,” said Alize Pharma’s President and Founder, Thierry Abribat. “It validates our medical approach, emphasizes our drug development capabilities, and fits well with our business strategy, which is to establish partnerships with the pharmaceutical industry early in the development of our programs in order to secure both near-term and long-term revenue streams.”

“We are delighted to reach this agreement with Alize Pharma. ASPAREC fits perfectly with EUSA’s specialty focus on oncology and orphan diseases and builds on our established portfolio in the field of acute lymphoblastic leukemia,” added Bryan Morton, President and CEO of EUSA Pharma. “This agreement follows the approval last year of EUSA’s first internally developed product and further underlines the company’s strategic transition into a fully fledged development as well as commercialization organization.”

Alize Pharma is a group of companies specialized in the development of innovative biopharmaceutical drugs, proteins, and peptides for the treatment of metabolic diseases and cancer. Its management is made up of a team of drug development experts and a board of directors offering wide international experience. Since its inception in 2007, the group has raised EUR 5 million with private and institutional investors. The first of the two entities of the Group, Alize Pharma SAS, is dedicated to AZP-01, a peptide derived from unacylated ghrelin, currently at the preclinical stage of development for the treatment of type II diabetes and other metabolic and cardiovascular indications. The second entity, Alize Pharma II SAS, is focused on the development of ASPAREC (AZP-02), a new PEGylated recombinant L-asparaginase for the treatment of ALL, currently in Phase I clinical development.

EUSA Pharma is a rapidly growing transatlantic specialty pharmaceutical company focused on oncology, oncology supportive care, and critical care products. The company has an established commercial infrastructure in the US, a pan-European presence, and a wider distribution network in numerous additional territories. EUSA currently has a total of 10 specialist hospital products, which are sold in over 80 countries globally.

Novozymes Wins Innovation Award for Ground-Breaking Half-Life Extension Platform

Novozymes Biopharma, part of Novozymes A/S, recently announced it has received the 2012 Drug Delivery Partnerships (DDP) Technology Innovation award for the company’s half-life extension platform. The award recognizes the most exciting delivery technology of the year. The albumin-based technology platform offers the potential to enhance patient quality of life through tailoring drug circulatory half-life to meet specific medical needs. The DDP awards acknowledge success within the drug delivery industry and were selected by peers from the pharmaceutical industry at the 16th annual DDP conference, held in Las Vegas, Nevada, January 2012. The award was collected by Dr. Darrell Sleep, Head of Research and Development, UK.

“Novozymes is delighted to have won the DDP technology innovation award,” said Dave Mead, Business Development Director, Novozymes Biopharma. “The albumin-based technology is adaptable and can be used for both genetic fusion (Albufuse Flex) or conjugation (Recombumin Flex), providing a unique ability to decrease or increase a drug’s half-life. Clearly this will help manufacturers to develop pharmaceuticals with enhanced pharmacokinetic properties, offering more favorable dosing regimes and improving patient compliance, while reducing healthcare costs. For the solution to be recognized as the most exciting delivery technology of the past year, at one of the pharmaceutical industry’s largest drug delivery conferences, is a real testament to its potential importance to the market.”

Lack of patient adherence to prescribed medications poses a tremendous challenge to the global healthcare community. The main reasons cited for poor compliance include patients’ forgetfulness and factors, such as the route of administration. To overcome these issues, the technology exploits the natural interaction between albumin and the neonatal Fc receptor (FcRn). In collaboration with the University of Oslo, specific albumin variants have been designed with altered binding affinities for the receptor, making it possible to modulate the serum half-life of an albumin molecule. By coupling a drug to these variants through genetic fusion or chemical conjugation, the technology confers the extended or reduced circulatory half-life onto the drug molecule.

The efficacy of biological drugs is often compromised due to short circulation time in the body. In parallel, many small molecule drugs are associated with toxicity issues due to non-specificity. This exciting half-life extension technology enables drug manufacturers to design new efficacious products, or life-cycle manage existing drugs, with longer serum half-life, reduced toxicity, and improved pharmacokinetic profiles. As a result, the frequency of injections a patient receives or even the amount of drug delivered can be reduced.

Novozymes is a world leader in bioinnovation. Together with customers across a broad array of industries, the company creates tomorrow’s industrial biosolutions, improving customers’ business and the use of our planet’s resources. With over 700 products used in 130 countries, Novozymes’ bioinnovations improve industrial performance and safeguard the world’s resources by offering superior and sustainable solutions for tomorrow’s ever-changing marketplace.

Merck KGaA Signs $550 Million Pact With Threshold Pharmaceuticals

Merck Serono, a division of Merck KGaA, Darmstadt, Germany, recently announced that a global agreement was signed with Threshold Pharmaceuticals, Inc., South San Francisco, to co-develop and commercialize TH-302, Threshold’s small molecule hypoxia-targeted drug. TH-302 is currently being investigated in a global Phase III clinical trial in patients with soft tissue sarcoma, a randomized Phase II trial in patients with advanced pancreatic cancer from which top-line results are expected in February, as well as additional clinical studies in other solid tumors and hematological malignancies.

Under the terms of the agreement, Merck will receive co-development rights, exclusive global commercialization rights, and will provide Threshold an option to co-commercialize the therapeutic in the US. In exchange, Threshold will receive an up-front payment of $25 million and could receive up to $35 million in additional development milestones during 2012. Threshold is also eligible to receive $20-million milestone payment based on positive results from its randomized Phase II trial in pancreatic cancer.

In the US, Threshold will have primary responsibility for development of TH-302 in the soft tissue sarcoma indication. Threshold and Merck KGaA will jointly develop TH-302 in all other cancer indications being pursued. Merck KGaA will pay 70% of worldwide development costs for TH-302.

Subject to FDA approval in the US, Merck KGaA will initially be responsible for commercialization of TH-302 with Threshold receiving a tiered, double-digit royalty on sales. Under the royalty-bearing portion of the agreement, Threshold retains the option to co-promote TH-302 in the US. Additionally, Threshold retains the option to co-commercialize TH-302, allowing the company to participate in up to 50% of the profits in the US, based on certain revenue tiers. Outside of the US, Merck KGaA will be solely responsible for the commercialization of TH-302 with Threshold receiving a tiered, double-digit royalty on sales in these territories.

“The addition of TH-302 to our pipeline provides an important opportunity in several different tumor types to expand our oncology development program,” said Susan Jane Herbert, Head of Global Business Development and Strategy, Merck Serono. “Given the fact that pancreatic cancer is a very difficult to treat indication, successful Phase II results could represent important upside for our company.”

“We are excited by the new resources that our partnership is going to bring to the development of TH-302, and the expertise in clinical development and commercialization that Merck will contribute to this program,” added Barry Selick, President and CEO of Threshold. “This collaboration provides Threshold a strong and committed partner with a shared vision for TH-302.”

TH-302 is a hypoxia-targeted drug that is thought to be activated under tumor hypoxic conditions, a hallmark for many cancer indications. Areas of low oxygen levels (hypoxia) within tissues are common in many solid tumors due to insufficient blood vessel growth. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be extremely hypoxic. TH-302 has been investigated in over 550 patients in Phase I/II clinical trials to date in a broad spectrum of tumor types, both as a monotherapy and in combination with chemotherapy treatments and other targeted cancer drugs.

Threshold has several ongoing clinical trials, including but not limited to, a controlled Phase II trial of TH-302 in combination with gemcitabine versus gemcitabine alone in patients with advanced pancreatic cancer and a Phase III study evaluating TH-302 in combination with doxorubicin versus doxorubicin alone in patients with soft tissue sarcoma. A Phase III trial of TH-302 in patients with first-line advanced soft tissue sarcoma (STS) was initiated in September, 2011, based on results from a Phase I/II trial investigating its use in combination with the chemotherapeutic doxorubicin. This randomized, multi-center Phase III trial will investigate the use of TH-302 plus doxorubicin compared with doxorubicin alone. The primary efficacy endpoint is overall survival. The study is conducted under a Special Protocol Assessment with the US FDA. It is being run in partnership with the Sarcoma Alliance for Research through Collaboration (SARC) and aims to enroll 450 patients with metastatic or locally advanced unresectable STS.

Results from a randomized, controlled, multi-center Phase II trial of TH-302 in patients with first-line pancreatic cancer are expected to be announced in February, 2012. This trial of 214 previously untreated patients with locally advanced unresectable or metastatic pancreatic adenocarcinoma started in June, 2010, and completed enrollment in June, 2011. Two different doses of TH-302 in combination with the chemotherapeutic gemcitabine were compared to gemcitabine alone, with progression free survival (PFS) as the primary endpoint.

STS refers to a heterogeneous and relatively rare group of tumors that develops in the soft, supporting tissues of the body. It can occur in any of the tissues that support, surround, or protect the organs of the body, such as muscle, fat, nerves, tendons, and ligaments or blood vessels. It can also develop in specific organs, including, for example, the uterus, stomach, skin, and small bowel. Occasionally it occurs in the head and neck. Adult STS is rare, with an estimated average incidence of 4 in 100,000 cases in Europe annually. In the US, there were an estimated 10,980 new cases and 3,920 deaths from STS in 2011. STS tends to occur in people over the age of 30, although certain types of sarcoma can develop more commonly in children and teenagers. Current treatment options for STS include surgery, chemotherapy, and radiotherapy, although response rates are generally low and side effects can be significant.