Aché

Aché’s portfolio is one of its greatest assets and is constantly evolving. Every year, the company earmarks about 10% of the cash generation to R&D initiatives, and aims to embed new technologies and knowledge to the process. The management comprises pure innovation projects (radical and incremental research) and development initiatives. From 161 projects which were under development in 2010, 143 – from the pharmacotechnical development area – should be added to the portfolio up to 2013.

Radical innovation

As the major front of growth among the major multinational pharmaceutical companies, the radical innovation presumes the research and development of molecules with pioneer characteristics, whether from the synthetic production, from biotechnological processes in bacterial or cellular cultures or from natural raw materials. Aché’s first experience in the area was Acheflan, the anti-inflamatory drug released to the market in 2004. By the end of 2010, Aché concentrated the radical research in nine projects (see chart). The creation of radical compounds involves a complex and long process (usually 8 to 12 years, on average) and highly-qualified multidisciplinary teams, in addition to cuttingedge equipment. Keeping the investments without a guaranteed success implies that companies should set out clear long-term goals and have stable decisions.

Among the molecules being currently developed by Aché, a part is in the stage of research, and another part undergoes assessments of technical and financial feasibility. The future of each one will be defined by results of the previous studies; some may be discarded while others could be added to the portfolio. For Aché, this is a risk already considered at planning. Although the whole process for building new knowledge is complex, a product that arrives to the market under patent protection represents a new path for medical treatment, and reflects on the company’s positioning.

Aché is dedicated to radical innovation research since the beginning of the decade, with an initial focus on phytotherapic products, and currently keeps projects of therapeutic appeal in different stages of the process, exploring new entities, either synthetic chemical or purified from natural sources. In addition to own initiatives, the company has been looking, in Technological Innovation Nuclei (TNI) from universities and research centers in Brazil, for the feasibility of creating molecules that could become new drugs. In 2010, the company started to create a radical research center with the purchase of the first pieces of equipment. The initiative is aimed at the development of new products and will be an important factor of agility and cost savings for

Phases

Incremental research

The creation of products which are analogue to already known molecules (incremental research) has the benefits of shorter achievement terms and higher rates of success. These higher chances of success are due to the fact that products have already passed the stage of safety and efficacy studies and tests. Existing drugs are the basis for improvement actions leading to new drugs with an equivalent structure and same functionality, but with biocharacteristics overcoming the ones of the original molecules (higher safety and potency or more durable action, for example). Since 2008, Aché has been intensifying the investments in this front, which has created about two thirds of all synthetic molecules used all over the world. By means of incremental research, the company diversifies its model of portfolio renewal and internalizes new technologies. In order to support the processes of chemical synthesis (which are usually linked to incremental innovation), Aché invests in bibliographic and patent research that guides the use of computing chemistry through specific software to handle molecular shaping and simulation. Along 2010, the company developed five molecules aimed at the central nervous system, at the respiratory system, at the cardiometabolic system, and at women’s health. By the end of the year, the company started the pre-clinical studies preceding the patent of one of the molecules, and filed the patent of another.

Pharmacotechnical development

When developing generics and branded generics, the company’s goals are improving the drugs and adapting them to the conveniences and needs of the consumer. This is a strategic competency. Up to 2017 in Brazil, the patent rights over 25 branded drugs leading the therapeutic class will expire, leaving room for a branded generics market assessed at R$ 2.8 billion. The competitive advantage will be favoring the companies having previous pharmacotechnical development and keeping an agile presence on the market. With its mastery on portfolio management processes, Aché has been getting ready to anticipate unique opportunities offered by this framework. The status of patents is permanently monitored by a team consisting of specialists from the pharmacotechnical development, legal, portfolio renewal, and supply departments. This structure cares for the process of including molecules in the development cycles of the company as a means of ensuring that the new drug may be launched as soon as its patent is in public domain. In this scope, Aché closed 2010 with the launch of 17 new products. The company has led 14 clinical studies for the renewal of registrations and new products, of which seven were implemented in 2010. In the segment of dermocosmetics, where the company has been increasingly extending its share, Aché now counts on 47 products.

Biotechnology

In the area of biotechnology, Aché’s purpose is securing its technological independence and adding competencies and value to business. Currently there are two biotechnological products under development with a short-term conclusion perspective; and from some moves in 2010, the company has set out the foundations to build on the medium term a dedicated industrial plant. The company is negotiating a partnership with the public sector which will involve the supply of a drug for treating multiple sclerosis (Interferon-beta 1-a) to the Ministry of Health, and the transfer of production technology to the Institute of Immunobiological Technologies Biomanguinhos, owned by Oswaldo Cruz Institute Foundation (Fiocruz). Since Brazil does not have any company with this manufacturing know-how, the Unified Health System (SUS) needs to deal with the international market and its high costs. The partnership will imply a cost reduction, and on the medium term it will bring the attainment of the technology needed to break the dependence relations. For Aché, the agreement will bring soundness to biotechnology business, providing a solid basis for the construction of its own factory. Biotechnology moves an increasingly larger portion of the global industry, providing efficient therapeutic responses in cases of high complexities, where no synthetic manufacturing technique is capable of replicating the substances from the biological processes. In some types of cancer, liver diseases and abnormal functioning of the central nervous system, the biotechnological drugs are the main treatment alternatives. Another example is dwarfism, for which the growth hormone, which is produced by biotechnology, is the main therapy available. Studies anticipate that from 2014 the biotechnological products will represent 50% of all drugs sold around the world based on the ongoing migration of major pharmaceutical companies to the segment as a means of making up for the loss of patents. The major companies of the sector are headquartered in the United States and Europe. In Brazil, the segment of biological products is still in its first stages, and usually depends on technologies from other countries. The company’s experiences in the area started with the research of phytomedicines (the first of which was Soyfemme, derived from soy), and based on this experience, the complexity of projects has been increasing. The regulatory aspect, as formulated now, presents restrictions to the participation of the Brazilian pharmaceutical industry. Aché supports the movements to change this reality, and by means of Farmabrasil–a social entity gathering major pharmaceutical companies in Brazil–, the company intends to deepen the discussions on the theme.

Phytomedicines Aché

• Acheflan® ointment and spray are the first medicine to be completely researched and developed in Brazil and prepared with the oil extract of Cordia verbenacea and indicated in the treatment of chronic tendinitis and muscle pains;
• Soyfemme®, based on soy isoflavones, for treating menopausal symptoms;
• Remilev®, composed of Valeriana officinalis (extract combination Ze 91019) and Humulus lupulus for treating sleep-related disorders;
• Remotiv®, based on Hypericum perforatum (extract combination Ze 117) and indicated in the treatment of light to moderate depression;
• Antilerg® made from Petasites hybridus and used in the treatment of allergic rhinitis;
• Dinaton®, based on Gingko biloba, for treatment of strokes;
• Kamillosan®, based on chamomile, for treating dermatitis.
• Sintocalmy®, based on Passiflora incarnata L. (extract ACH06), indicated in the treatment of anxiety.

Acheflan®: a success story

Twenty years ago, one of the founders of Aché, Victor Siaulys, based on his own positive experience with a Brazilian medicinal plant, had the idea and the vision to research and develop medicines taking advantage of the rich Brazilian flora. This dream and project was almost abandoned several times, due to the countless difficulties that he faced. His persistence, however, enabled us to arrive at Acheflan®, the first medical product totally researched and developed in Brazil. Acheflan®: made with Brazilian raw materials, researched by Brazilian scientists, in Brazilian universities, and developed and launched by the largest Brazilian pharmaceutical laboratory. We went through all the same R&D stages as for a synthetic medicine, we even compared Acheflan® ointment to the best-selling standard synthetic drug, and the conclusion was that Acheflan® was just as safe and effective as the standard, with a statistical trend towards being superior. We have already been sounded out by seven international companies for some type of partnership with Acheflan® and we are holding talks with a view to exporting it. We have filed patent applications for the oil extract and the active ingredient, and the systemic administration form is in the research and development stage. The success of this medicine was reaffirmed in January 2007, when a new form was launched: Acheflan® spray.