Activartis Develops Cancer Vaccine in Phase II, Seeks Partner

Activartis GmbH (formerly Trimed Biotech GmbH) recently announced it is developing a cancer immunotherapy concept that is currently in Phase II clinical trials. Initially directed against aggressive brain cancer, it will in principle be applicable to all types of cancerous diseases and therefore has blockbuster potential. The therapeutic platform combines a completely novel proprietary and IP-protected approach (the utilization of a bacterial danger signal in combination with the patient’s tumor antigens) with a proven successful concept (dendritic cells) to mobilize the patient’s immune system to combat the disease.

The Activartis proprietary technology platform focuses on dendritic cells (DCs), the key regulatory elements of the immune system. To trigger an immune response against tumor cells, the immune system’s tolerance of cancer cells must be overridden. By presenting a bacterial danger signal (LPS, lipopolysaccharide) in combination with the patient’s tumor antigens to the patient’s dendritic cells, Activartis’ therapeutic agent tricks the cells into recognizing the tumor as dangerous, which triggers an immune reaction to the tumor antigens. The DCs then activate tumor-specific T cells (including the killer T cells that attack tumor cells) to destroy tumor tissue. The Activartis therapeutic concept is the first active immune therapy that activates release of the immune modulatory cytokine interleukin 12 (IL-12), a signaling molecule that is of central importance in polarizing an immune response based on killer T cell activity.

The proprietary technology involved is part of a trend-setting approach to individualized medicine. Utilizing the patient’s own tumor tissue, Activartis aims to mobilize the patient’s immune system to develop a tailored immune response to their specific tumor in order to recognize and destroy the disease. The therapy is therefore, in principle, applicable to all cancerous diseases.

Autologous dendritic cell therapies represent a major milestone in the development of cancer immune therapy and a paradigm shift in cancer treatment. In April 2010, the FDA approved the first autologous dendritic cell therapy for the treatment of advanced prostate cancer. However, the use of an antigen specific to a particular tumor means that it cannot be used against other cancers. The technology is also highly dependent on antigen selection and is exposed to the potential variability of cancers in different patients.

The Activartis cancer vaccine technology eliminates these drawbacks by employing a more advanced technology, which uses the complete spectrum of tumor antigens unique to an individual patient’s cancer.

The handling and logistics requirements for Activartis therapeutic agents are more simple and less complicated to manage. The agents may be frozen, conserved, and shipped, meaning that a patient’s whole course of treatment can be produced at one time. Outpatient treatment of the patients is completed in minutes.

Currently, Activartis is testing its therapy in a randomized, open-label, two-arm, multi-center, Phase II clinical study of glioblastoma multiforme (GBM) at eight clinical institutions in Austria, including three university hospitals. GBM is the most aggressive and lethal form of brain cancer. The disease often progresses rapidly, and prognosis is nearly always poor (median survival is approximately 14 months). The primary objective of the study is progression-free survival, with overall survival as the secondary goal. The interim results of the study are expected to be available in the second half of 2012.

The safety and efficacy of Activartis’ therapeutic agent has been demonstrated in four Phase I pilot studies, including more than 100 patients with different indications (brain, bone, kidney, prostate cancer, and a heterogenous selection of pediatric cancers). Clinical development is backed by AOP Orphan Pharmaceuticals, an Austrian pharmaceuticals company that acquired Activartis in 2006. The partners plan to apply for orphan drug designation. Following successful completion of Phase II, Activartis and AOP Orphan are planning to collaborate with an industrial partner who will co-sponsor Phase III clinical development, manufacturing, registration, and market launch as well as the clinical development of Activartis DC cancer vaccine technology for further indications.

Activartis (originally Trimed) was founded by Vienna cancer researcher Thomas Felzmann, MD, in 2003 as a spin-off from the renowned St. Anna Children’s Cancer Research Institute. Patents filed in 2002 have been granted in most relevant markets. A US patent for IL-12 secreting DCs was granted early in 2011. In 2006, Activartis was acquired by AOP Orphan Pharmaceuticals, which was founded in 1997 and is headquartered in Vienna. AOP Orphan is a leader in the clinical development and distribution of drugs for rare diseases.

3M DDS Announces New VP & General Manager

3M Drug Delivery Systems recently announced the appointment of James Ingebrand as the new Vice President and General Manager after the retirement of his predecessor, James Vaughan. Mr. Ingebrand has built a 27-year career at 3M, giving him significant insight into the pharmaceutical and healthcare industries.

As Vice President and General Manager, he will assume responsibility for the strategic direction of 3M Drug Delivery Systems’ inhalation, transdermal, topical, and oral drug delivery devices and components, which are manufactured and sold in more than 60 countries and six continents around the world.

“We are pleased to have Jim step into this new role within 3M,” said Brad Sauer, Executive Vice President, 3M Health Care Business. “Jim’s depth of knowledge and understanding of the pharmaceutical industry equip him with outstanding tools to cultivate the innovation that 3M Drug Delivery Systems is known for.”

Mr. Ingebrand’s previous positions within the 3M Drug Delivery Systems Division include roles as a Key Account Manager in the United Kingdom, an Inhalation Program Manager, and a Six Sigma Black Belt. He most recently served as the Global Business Director for the 3M Dental Division and has worked in several other healthcare divisions of 3M, including the 3M Infection Prevention Division and 3M Health Care Specialties Division.

Mr. Ingebrand started his career at 3M in 1984 as a Marketing Analyst in the Corporate Marketing Research Department. He earned his BS in Biochemistry and his MBA from the University of Minnesota.

3M Drug Delivery Systems partners with pharmaceutical and biotech companies to develop pharmaceuticals using 3M’s inhalation or transdermal drug delivery technology. 3M offers a full range of feasibility, development, and manufacturing capabilities combined with regulatory guidance to help bring products to market. In-house resources, including toxicology, regulatory expertise, quality assurance, operations, and marketed product support, are available for each step of the development and commercialization process. This depth of resources is one reason why more than 50% of all metered-dose inhalers worldwide and 80% of all transdermal systems in the US utilize 3M drug delivery technology.

Bio-Images & Medimetrics Partner to Deliver Next-Generation Smart Pill Technology

Bio-Images Research and Medimetrics Personalized Drug Delivery recently announced a partnership to introduce the IntelliCap to the global pharmaceutical industry as a clinical research tool. The announcement was made at the annual meeting of the American Association of Pharmaceutical Scientists this past October in Washington, DC.

Medimetrics’ IntelliCap is the first device that allows patient-specific drug delivery by combining electronically controlled drug delivery with patient monitoring and real-time communication/interaction with the patient. Bio-Images Research is an established leader in the clinical study of pharmaceuticals using scintigraphic imaging. In partnership with Medimetrics, they will now offer IntelliCap as an advanced tool for regional absorption studies in man, supported by a full clinical trial design and management package.

The technology will reduce the time it takes to bring new drugs safely to market by allowing rapid identification of promising drug candidates while quickly eliminating potential failures. This is currently only possible at a much later stage, after substantial R&D costs have been incurred.

“We are looking forward to bringing our scintigraphy and clinical research expertise to this exciting partnership to provide clients with an outstanding drug development tool,” said Professor Howard Stevens, cChairman of Bio-Images Research.

“IntelliCap is an extremely powerful tool for the development of new drugs. It allows directly relevant, minimally invasive, repeatable assessment of candidate drugs, new formulations or functional food performance to be organized and completed quickly and with ease. The partnership with Bio-Images allows us to offer broader service packages to our pharma customers,” added Dr. Olaf Weiner, CEO of Medimetrics.

IntelliCap is a wirelessly controlled electronic capsule system that delivers formulations to user-defined regions of the gastrointestinal tract for regional absorption studies. This is an essential step in lead candidate screening, formulation development, and the development of drug delivery systems. The 11 mm x 26 mm CE-marked device is made up of a microprocessor, battery, pH sensor, temperature sensor, RF wireless transceiver, fluid pump, and drug reservoir. It communicates via its wireless transceiver to an external control unit worn by the test subject.

This groundbreaking technology allows pharma researchers to tailor delivery profiles in response to pH and temperature readings returned from the capsule as often as every 10 seconds, indicating its location in the GI tract at any given moment. The ability to customize the delivery of profiles in this way is a significant improvement on existing wireless capsule systems, which allow only one pulse of drug release.

Bio-Images Research Ltd is a UK-based clinical research company founded in 2000. The company undertakes contract clinical research on drug delivery systems, chiefly using the non-invasive nuclear imaging technique of gamma scintigraphy to assess formulation behavior in man. The company is part of the Bio-Images Group, which incorporates formulation development company, Drug Delivery International, and offers a high level of expertise in drug delivery systems.

IntelliCap was originally developed in 2008 as a research tool under the Philips Medimetrics brand name. The expanding market has seen the emergence of Medimetrics Personalized Drug Delivery B.V. as a fully fledged biotech company in its own right. The new entity, a Philips-associated company, has also won substantial backing from Germany-based Zukunftsfonds Heilbronn GmbH & Co KG. The company’s headquarters are in Heilbronn, Germany, with research labs, service centers, and administrative offices in Europe (Eindhoven, The Netherlands) and the US (New York).

Encap Drug Delivery & Lena Nanoceutics to Develop Nano-Capsule Technology

Encap Drug Delivery and Lena Nanoceutics recently announced a collaboration agreement to develop a new drug delivery technology (Nano-Capsules) that combines Lena‘s proprietary nanoparticle engineering technology with Encap’s liquid filled hard capsule technology.

One of the major challenges in oral drug delivery is the development of formulations for improved absorption of poorly soluble and poorly absorbed drugs. There are a number of technologies available to enhance bioavailability, amongst others nanocrystals or nanoparticles, and liquid fill formulations. The nanoparticle approach results in a decrease in particle size, an increased surface area, and therefore a faster dissolution. In some cases, this has been demonstrated to result in increased bioavailability of the active drug. Liquid fill formulations, which can be solutions or suspensions of drug in non-aqueous liquids, have also proven in many cases to produce significant bioavailability enhancement.

“We believe there are considerable synergies to be achieved by combining the nanoparticle and liquid fill technologies particularly for low solubility and low permeability compounds,” said Dr. Stephen Brown, CEO at Encap. “Lena Nanoceutics has made very significant advances in the science and engineering of particle milling, and we are delighted to be collaborating with them on this important project.”

Preliminary in vitro data generated using itraconazole as a model compound has shown improved dissolution rate when both nanoparticulate and liquid fill formulations were compared to standard particulate drug formulations. More interestingly, an even greater improvement was found when the nanoparticle technology was combined with liquid fill technology.

Encap was established in 1989 and is a global provider of oral drug delivery and pharmaceutical development services. The company provides clients with fully integrated analytical and formulation development services, clinical trial manufacturing, and high-volume commercial manufacturing. Encap’s state-of-the-art facility in the UK is the world’s largest development and manufacturing facility dedicated to liquid and semi-solid filled hard capsules.

Lena Nanoceutics Ltd is a technology company providing enhanced nanoparticle-based formulations, addressing issues such as poor bioavailability for pharmaceutical and healthcare products. This is achieved through the application of its efficient proprietary particle size reduction system together with significant expertise in formulation and drug delivery. Lena Nanoceutics’ strategy focuses on collaboration with clients to develop innovative solutions that are readily scalable to production levels.

Biogen Idec & Portola Pharmaceuticals Strike $553-Million Deal

Biogen Idec and Portola Pharmaceuticals, Inc. recently announced they have entered into an exclusive, worldwide collaboration and license agreement under which both companies will develop and commercialize highly selective, novel oral Syk inhibitors for the treatment of various autoimmune and inflammatory diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

The collaboration’s lead molecule, PRT062607, has been shown to be a highly potent and specific oral inhibitor of Syk in a broad panel of in vitro kinase and cellular assays and is currently in Phase I studies. Results of the studies to date suggest the compound is well tolerated and has a profile suitable for once-daily dosing.

Under the terms of the agreement, Biogen Idec will provide Portola with an up-front payment of $36 million in cash and purchase $9 million in Portola equity, with additional payments of up to $508.5 million based on the achievement of certain development and regulatory milestones. Biogen Idec will lead the global development and commercialization efforts for the Syk inhibitor program in major indications, such as RA and lupus, while Portola will lead US development and commercialization efforts for select smaller indications as well as discovery efforts for follow-on Syk inhibitors. Portola retains an option to co-promote alongside Biogen Idec in the US in major indications. Worldwide costs and profits will be split by Biogen and Portola 75% and 25%, respectively.

“We are enthusiastic to be working with Portola to advance its Syk inhibitor as a potential treatment for autoimmune diseases,” said George A. Scangos, PhD, CEO of Biogen Idec. “This program is an excellent strategic fit with our focus on immunology. Portola is a high-quality company with a great track-record in small molecules, and we have crafted a collaboration that truly is a win for both companies. We will now focus on a thoughtful and aggressive program to fully explore the potential of Portola’s compounds against this very interesting target, with the goal of creating an effective, safe, and convenient oral treatment for patients with debilitating autoimmune and inflammatory diseases.”

“A significant portion of people with RA do not respond to currently approved treatments or have only modest responses, and treatment options for lupus are limited,” added Doug Williams, PhD, Executive Vice President, Research and Development of Biogen Idec. “Inhibition of Syk has the potential to provide effective, well-tolerated therapies for patients with these and other autoimmune diseases. We are encouraged by the preclinical and clinical data to date and see an opportunity to develop a best-in-class, highly selective oral treatment for these devastating diseases. This program plays to our strengths and experience in immunology, particularly B-cell biology, reflects our focus on cutting-edge science, and strengthens our early-stage pipeline.”

Biogen Idec uses cutting-edge science to discover, develop, manufacture, and market therapies for serious diseases with a focus on neurology, immunology, and hemophilia. Founded in 1978, Biogen Idec is the world’s oldest independent biotechnology company. Patients worldwide benefit from its leading multiple sclerosis therapies, and the company generates more than $4 billion in annual revenues.

Portola Pharmaceuticals discovers and develops innovative therapeutics based on targets with established proof-of-concept that are designed to provide significant advances over current treatments for cardiovascular and autoimmune/inflammatory diseases. Portola scientists have successfully collaborated for over 15 years on the discovery and development of novel small molecule agents targeting platelets, coagulation pathways, and protein kinases. In thrombosis, Portola is independently developing betrixaban, a Phase III-ready, long-acting, oral direct Factor Xa inhibitor, and its companion product, PRT064445, a recombinant Factor Xa inhibitor antidote.

Acton Pharmaceuticals Announces License Agreement for Nasal Aerosol

Acton Pharmaceuticals, Inc. recently announced it has completed a licensing agreement with Sanofi US for prescription NASACORT HFA (triamcinolone acetonide) Nasal Aerosol for the treatment of nasal allergy symptoms. Under the agreement, Acton assumes the exclusive US rights to develop and market NASACORT HFA in the $2-billion prescription nasal steroid market.

NASACORT HFA is an intranasal steroid formulated with a hydrofluoroalkane (HFA) propellant and delivered as a fine, dry mist in a small volume pressurized metered dose. Currently, only aqueous (AQ) or water-based liquid spray formulations of nasal steroids are available in the US. Under the agreement, Sanofi retains all rights to NASACORT AQ.

Acton‘s research and development strategy is to apply our extensive chemistry experience to resolve manufacturing issues that often plague aerosol products during the FDA approval process,” said Daniel Kreisler of Acton Pharmaceuticals. “The NASACORT HFA’s NDA was an FDA-approved aerosol product but was not commercially launched due to technical reasons related to manufacturing scale up. We believe we can launch this important product into market. NASACORT HFA is another example of a commercial opportunity that targets a multi-billion dollar respiratory market.”

NASACORT HFA is in development as a once-a-day treatment for nasal symptoms associated with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) in adults and children 6 years of age and older. To date, Sanofi has conducted two Phase III studies of NASACORT HFA in clinical trials involving more than 1,100 patients. The most common adverse events reported in clinical studies (>3%) were sneezing, headache, nasal irritation, and rhinitis.

In addition to NASACORT HFA, Acton is currently developing AEROSPAN (flunisolide HFA) Inhalation Aerosol. AEROSPAN is an HFA-propelled aerosol inhaled corticosteroid (ICS) for the treatment of asthma. AEROSPAN is the first HFA inhaled steroid to incorporate a built-in spacer device, designed to assist patients in delivering their medication to the lungs. The NDA for AEROSPAN was FDA approved in 2006, and Acton licensed AEROSPAN from Forest Laboratories, Inc. in 2009 and plans to commercialize AEROSPAN upon completion of certain manufacturing requirements.

“The therapeutic indications of NASACORT HFA and AEROSPAN are complementary and will enable us to provide a highly targeted commercial effort directed toward respiratory and pediatric physicians,” stated John Simon of Acton Pharmaceuticals. “The size and scale of these markets combined with the peak sales potential of these products will enable us to further expand our reach among primary care physicians with a larger commercial partner.”

In clinical trials, AEROSPAN was generally well tolerated. In AEROSPAN’s clinical trials, the most common adverse events (>3%) were headache, fever, allergic reaction, bacterial infection, pain and back pain, vomiting, dyspepsia, pharyngitis, rhinitis, cough, sinusitis, epistaxis, rash, and urinary tract infection. Combined, the inhaled and nasal steroid markets are valued at approximately $9 billion in the US.

The clinical program of NASACORT HFA Nasal Aerosol included two Phase III studies conducted in the US that involved 1,176 patients 12 to 83 years of age with allergic rhinitis, of which 729 patients were treated with NASACORT HFA Nasal Aerosol. One study was a 2-week, double-blind, parallel-group, placebo-controlled trial comparing NASACORT HFA Nasal Aerosol to NASACORT Nasal Inhaler (triamcinolone acetonide CFC formulation) in 780 patients 18 years of age and older with seasonal allergic rhinitis.

In the 2-week, double-blind study, NASACORT HFA Nasal Aerosol and NASACORT Nasal Inhaler (triamcinolone acetonide CFC formulation) were comparable, and both formulations showed a statistically significant reduction in symptoms of allergic rhinitis. There were no significant differences in the effectiveness of NASACORT HFA Nasal Aerosol across subgroups of patients defined by gender, age, or race.

The second study was a 12-month open-label safety in 396 patients with perennial allergic rhinitis. Adverse events occurring with an incidence of 3% or greater and more commonly with NASACORT HFA Nasal Aerosol arms compared to placebo irrespective of drug relationship include sneezing, headache, nasal irritation, and rhinitis.

Acton is a specialty respiratory pharmaceutical company dedicated to developing prescription drugs to improve the well-being of patients. Acton‘s corporate headquarters are located in Marlborough, MA.

Share This