Press Room

Press Release / Nov 05, 2001

Hovione's Antibiotic Doxycycline Joins Fight Against Anthrax

Hovione FarmaCiencia SA is using one of its oldest products to fight the world's newest terrorist threat.

Lisbon, Nov. 5 (Bloomberg) -- Hovione FarmaCiencia SA is using one of its oldest products to fight the world's newest terrorist threat.
The Portuguese company makes doxycycline, an antibiotic that U.S. authorities are increasingly choosing to treat anthrax over Bayer AG's more expensive Cipro, which they used after the initial cases of exposure to the potentially deadly bacteria.
After almost 20 years of selling doxycycline to treat respiratory disorders, sexually transmitted diseases, even an outbreak of plague in India, Hovione says it's able to quickly boost production to meet the increased demand. In fact, it's done so before.
``Ten years ago, before Desert Storm, it was exactly the same situation,'' Chief Executive Officer Guy Villax said in an interview. ``Every soldier that went to Desert Storm had their doses of doxycycline in anticipation for bio-warfare,'' and soldiers who went to Somalia did the same.
``Whenever there's this type of emergency, we have to find solutions,'' he said.

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Hovione says it accounts for about 75 percent of the U.S. market for doxycycline, a generic drug. The family-controlled chemicals company exports the active ingredient for doxycycline to companies in the U.S. and about 30 other countries that put the ingredient into pills.
The company started preparing to boost production when it received a surge in hits on its Web page about doxycycline, soon after the Sept. 11 terrorist attacks, as people anticipated the possibility of bio-terrorism.
``We got our act together in terms of reorganizing production, redefining priorities, getting in touch with our raw-materials suppliers to put the supply chains in place,'' Villax said.
Hovione makes doxycycline at its plant in Macau, the former Portuguese colony governed by China since 1999. Hovione's near Lisbon boasts two Chinese statues of lions at the gates. The Portugal plant may pitch in to meet the increased demand, Villax said.

Demand Peaks

The U.S. government is ordering enough doxycycline to treat 20 million people for 60 days, Villax said. ``We know we are facing a peak in demand because of all this stockpiling,'' he added. ``We can produce large quantities very fast, but I cannot imagine that this rush is going to last beyond (the first quarter) of next year, and by that time there will be ample stocks and the concern with shortage will disappear.''
Besides costing about one fourth as much as Cipro, doxycycline is gaining acceptance as a safer drug for dealing with anthrax, with fewer side effects. After a report by the U.S. Centers for Disease Control last month recommended the use of doxycycline, officials in Washington who had provided Cipro to thousands of postal and government workers switched to the generic drug.
Doxycycline accounts for less than 10 percent of Hovione's annual sales of about $70 million, Villax said. ``It's an old product, and having regard for its life cycle, it's still a good money earner,'' he added. Antibiotics gradually give way to replacements as bacteria become more resistant and companies promote new products.
``I really think the future of the company is the fact that half our sales are (from) products launched less than five years ago,'' he said. Revenue has almost tripled from $25 million in 1995. The company doesn't disclose profits, though Villax said it's always had an operating profit since it started large-scale production in the 1970s.

Hungarian Roots

``Hovione is a respected player, with a high-quality image,'' said Enrico Polastro, senior analyst for European pharmaceuticals and fine chemicals at Arthur D. Little Inc. 
Villax's father, Ivan Villax, immigrated to Portugal in 1951 and started the company with two other natives of Hungary in 1959. Letters from the founders' names -- Horty, Villax and Onody --were combined for the company name. Ivan Villax's two partners later sold their shares, and he's still the company chairman.
``In the whole of the 60s, we were just a lab in the basement,'' Guy Villax said. ``Occasionally the basement exploded, and the kids were woken up, and that was our momma-and-poppa shop.''
Industrial-scale production began in the 1970s, selling Japanese companies ingredients for use in anti-inflammatory creams and anti-asthma pumps. In the 1980s, as many antibiotics' patents expired, Hovione joined the trend of companies making generic drugs.

Right Chemistry

The most recent round of growth comes from ``outsourcing'' work, producing pharmaceutical ingredients on behalf of specific drug and biotechnology companies.
``Big Pharma went through a major restructuring, spinning off the chemistry, consolidating,'' Villax said. ``At the same time, you had the emergence of all the biotech sector at Nasdaq, with tremendous amounts of capital to invest in drug discovery. And someone has to do the chemistry.''
Hovione aims to get half its revenue from generic drugs and half from outsourcing work, Villax said.
The company's shareholders include Hovione employees, plus some of the chairman's business associates from other ventures, though it has no plans to sell shares in the market, the CEO said.
Larger companies have approached Hovione about a possible purchase, he added, though he's skeptical about the benefits for customers, ``and I think that's what matters at the end of the day.''

--Jim Silver in the Lisbon bureau (351-21) 340-4545, or jsilver@bloomberg.net

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International Pharmaceutical Industry journal speaks with Márcio Temtem, VP Strategic Business Management at Hovione, about how the company’s deep-rooted expertise in complex chemistry differentiates it within the CDMO landscape, enables seamless integration from drug substance to drug product, and supports partners in accelerating the development of high-potency APIs, advanced formulations, and next-generation therapeutic modalities. How does your complex chemistry expertise differentiate you from other CDMOs and how does it translate into helping partners accelerate the development of increasingly sophisticated APIs and formulations? Hovione has been associated with complex chemistry since its genesis. The company started by developing very tough chemistry on corticosteroids and antibiotics, which was an expertise that in the 90s we transferred into the contract manufacturing business.  Since then, Hovione has been exploring chemistry and its complexity in contract manufacturing through several angles. One is the ability to have assets across the globe and at different scales that allow the company to address various client needs. Another example of being able to tackle the complexity is having assets that can address molecules with different levels of potency. High potency is something that we offer in many of our facilities. Over the years, we have also tackled chemistries that are difficult to manage, like hydrogenations and cryogenic reactions. All these are part of a menu that we offer into the services. Hovione is always attentive to the client’s needs. The next step after chemistry, which typically tends to be particle engineering, either by means of crystallisation, controlled crystallisation, jet milling, or one of the technologies that we master most, spray drying. We keep attentive to these needs and we keep upgrading our toolbox with new hardware and new software. On the hardware side, we recently announced a partnership with Microinnova to embed continuous flow into our offering. On the software side, we have added micellar chemistry, a water-based approach to chemically synthesise active ingredients, addressing sustainability within the broader pharmaceutical industry. How does your manufacturing approach ensure seamless integration from drug substance to drug product both technically and operationally? Hovione has sites located in Europe, Asia, and North America, designed to offer clients a seamless, integrated approach across our network, not only in terms of processes, but also in terms of technologies. These facilities serve clients globally, although naturally some clients favour the local site. In terms of integration, Hovione offers the synthesis of the active ingredient, the manufacturing of intermediates such as amorphous solid dispersions, and the final drug product all in one site. Many companies claim to offer integrated services, but they do this across multiple sites. Hovione does the integration at one site, which reduces hand-offs, streamlines operations and ensures technical alignment. How do technologies such as spray drying and particle engineering, when combined with your chemistry expertise, enhance formulation performance and streamline scale-up timelines? Spray drying has become one of the most versatile technologies in our industry. It addresses challenges that both chemists and formulators face. Chemists are often concerned with problems such as yield, purity or ways of obtaining the right solid-state characteristics of the API, such as polymorphic form. Spray drying can provide a means of isolating materials that are very difficult to isolate by other methods. Examples of compounds that benefit from this include peptides and sugars. On the formulation side, spray drying addresses one of the biggest challenges in the industry: the poor solubility and consequently bioavailability of most of the new drugs. Seventy to ninety per cent of the new drugs in development are poorly soluble. Over the past 20 years, Hovione has developed a platform for making amorphous solid dispersions by spray drying. This platform allows new formulations to be developed with minimum quantities of API and in a short number of few weeks. The technology provides a seamless scale-up from grams to tons, gives clients line-of-sight to commercial production, and saves valuable API at early stages of development. It also allows integration between drug substance and drug product, linking synthesis, intermediate manufacture, and final product in a single site, which is unique in the industry. As molecules and processes become more complex, so too do supply chains. How does Hovione ensure consistency, quality, and regulatory confidence across global operations? Hovione maintains consistency, quality and regulatory confidence through a combination of global assets, standardised platforms and processes, and cross-functional expertise. Our sites are designed to serve global clients while maintaining local responsiveness. We offer high-potency capabilities and advanced particle engineering to address complex molecular challenges. By standardising technologies and processes across sites, Hovione ensures predictable outcomes and adherence to global regulatory requirements. This integrated approach supports reliable supply chains even as molecules and processes grow more complex. With the rise of HPAPIs, novel excipients, and emerging therapeutic modalities, how is Hovione evolving its chemistry and process capabilities to support the next generation of pharmaceutical innovation? We see a trend towards more complex molecules and increasing demand for high-potency compounds. Hovione continues to invest globally, expanding capabilities in high-potency APIs, novel excipients, emerging modalities, and emerging delivery routes such as inhalation or nasal delivery. Chemistry is used as a tool to enable these delivery routes, including synthesis, crystallisation to achieve the right polymorphic form, shape, and size, and optimisation of interactions with excipients. All this is interconnected with our platforms, and amorphous solid dispersions by spray drying, designed to improve bioavailability, the one with the most market credits. Our capabilities bridge drug substance and drug product development and allow us to serve commercial products of different volumes, from small batches to larger scales, all while handling high potency and complex chemistries.   Read the full article at International-Pharma.com  

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