Indena Steps Up | May 30, 2011 Issue - Vol. 89 Issue 22 | Chemical & Engineering News
Volume 89 Issue 22 | pp. 32-34
Issue Date: May 30, 2011

Indena Steps Up

Extracts and API producer makes its own drug discoveries to keep ahead of competitors
Department: Business
Keywords: plant extracts, active pharmaceutical ingredients, cancer drugs, nutritional supplements
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With care
A worker handles a cytotoxic and high-potency compound in a glove box at Indena’s Settala, Italy, site.
Credit: Indena
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With care
A worker handles a cytotoxic and high-potency compound in a glove box at Indena’s Settala, Italy, site.
Credit: Indena

Readiness to adapt to changing times and market conditions has enabled Indena, a privately held Italian medicinal and nutritional plant extracts specialist, to survive for 90 years.

The company’s annual sales grew to $200 million mainly by making custom active pharmaceutical ingredients (APIs) for drug firms and standardized plant extracts for nutritional supplement makers. Now it is conducting internal research programs to discover, patent, and license its own drugs. And it has started up a new business to make single-dose nutritional supplements for sale by prescription in Italy.

Over many years, explains Dario Bonacorsi, the company’s president, Indena became expert in scaling up the extraction and purification of APIs from plant sources. Success led to a long list of process patents. But such patents are no guarantee that a customer will buy only from Indena.

“As you know, others can develop processes of their own to compete at lower cost,” says Bonacorsi, a Ph.D. electrical engineer and a 30-year veteran of the company. Players include not only U.S. and European fine chemicals makers but also a host of new Asian firms that often bring to market lower cost products.

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A little more than 10 years ago, Bonacorsi started to dedicate a portion of Indena’s R&D budget to develop new chemical entities. One, a taxane known as ortataxel, is a drug for solid tumors in Phase II clinical trials. Licensed to Spectrum Pharmaceuticals in 2007, the drug is in the same family as paclitaxel, the pioneering ovarian and breast cancer treatment derived from the yew tree.

Indena is developing two other novel entities, both derivatives of colchicine, an extract from the autumn crocus. One has potential as a muscle relaxant and is licensed to an Italian drug firm. The other is a cytotoxic molecule that may be useful to treat colon tumors and has been licensed to Celegene via Abraxis Bioscience.

In addition, Indena is developing a DNA-derived therapeutic oncology vaccine from animal and human cell sources for which it has recently filed an Investigational New Drug Application. As evidence of its potential, Bonacorsi notes that the U.S. Food & Drug Administration last year approved Dendreon’s Provenge (sipuleucel-T), the first vaccine for metastatic prostate cancer. Indena also has high hopes for a therapeutic aid to counter the effects of radiation on cancer patients, which it is also developing on its own.

In working on these and other potentially useful molecules, Indena does much of the phytochemistry research it is known for at its Settala, Italy, production and R&D complex, Bonacorsi says. For efficacy testing, it joins with outside academic and clinical researchers including the University of Texas M.D. Anderson Cancer Center, in Houston, and Karmanos Cancer Institute, in Detroit.

In nutritional supplements too, the firm has taken a new approach. Although it continues to supply standardized extracts to nutritional supplement formulators, Indena has just introduced what Bonacorsi calls a line of “ethical supplements.” They are meant to be sold by prescription through pharmacies under a label incorporating the names of the firm’s founders: Carlo Boccaccio Inverni and Biagio Alberto Della Beffa.

The first of the supplements helps people lose weight and stay on a diet. “Developed with a pharmaceutical attitude,” the ingredients are obtained from edible plants, Bonacorsi says. They promote a feeling of satiety, help regulate blood sugar levels, and act as a diuretic.

Bonacorsi attributes Indena’s current focus on its own patented discoveries to a rough period in the pharmaceutical and nutritional supplements markets that began around 2000. Like many lean periods, this one came after a time of plenty.

In 1992, Bristol-Myers Squibb (BMS) gained approval to market paclitaxel, known as Taxol, in the U.S. and Canada. At first, huge quantities of the endangered Pacific yew tree were needed to make the drug. However, scientists discovered that it could instead be made from an intermediate obtained from needles of Taxus baccata, the common English yew. BMS turned to Indena, which had developed a process to extract the intermediate, 10-deacetylbaccatin (10-DAB).

The relationship was profitable for Indena until 2000, when BMS lost patent protection on its process for making paclitaxel and generics began to enter the market. “Overnight, BMS decreased the price of Taxol by 70% to keep volumes high,” Bonacorsi says. Indena had to accept the new reality. “We kept our 10-DAB volumes, but we had to review our prices,” he says.

A similar decline occurred in the nutraceutical market. In the mid-1980s, Indena began to develop a market in the U.S. for nutritional supplements based on extracts from plants such as Gingko biloba, ginseng, grape seed, and saw palmetto. Until then, most dietary supplements sold over the counter in the U.S. were vitamins and minerals.

PROCESSED
Reaction vessels at Indena facility in Settala.
Credit: Indena (Both)
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PROCESSED
Reaction vessels at Indena facility in Settala.
Credit: Indena (Both)

“We practically transferred to the U.S. ingredients that in Europe were considered active pharmaceutical products and were produced according to Good Manufacturing Practices,” Bonacorsi says. And in doing so, “we created quite a nice market for ourselves and our customers.” Initially, the supplements market grew through specialty shops, mail order, and direct-to-consumer sales.

Then, at about the same time that paclitaxel went generic, mass market retailers became interested in the supplements category. “It was a disaster for Indena,” Bonacorsi recalls. “The mass market is not interested in quality but in low prices.” Chinese and Indian producers entered the U.S. nutritional supplement market and “our sales decreased dramatically,” he says.

Indena’s balance sheet took a hit, Bonacorsi says, but the firm had sufficient capital on hand to weather the storm. It also had—and still has—no bank debt. “We are still private because we don’t need to bring in outside capital,” he explains. Heirs of one of Indena’s founders, Della Beffa, still control and guide the firm, he notes.

Now, by discovering its own new drugs the firm expects to move beyond traditional custom manufacturing and gain revenues from royalties and option fees, Bonacorsi says. Spectrum, for instance, paid Indena $2.8 million when it first licensed ortataxel and promised to make milestone and royalty payments.

With the new line of ethical dietary supplements, Bonacorsi says, Indena has patented both the extracts and the process to make them. The branded products should be shielded somewhat from price competition, he says, and are candidates for licensing to markets outside of Italy.

Bonacorsi
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Bonacorsi

James R. Bruno, president of Chemical & Pharmaceutical Solutions, a pharmaceutical industry consulting firm, says Indena’s work on taxane derivatives “plays well into their strengths,” which include the ability to make high-purity extracts and handle highly potent compounds.

However, Bruno is skeptical of Indena’s plan to compete in the dietary supplements area with prescription extracts. As an example, he says St. John’s wort, an herbal treatment for depression, is St. John’s wort whether it is sold over the counter or by prescription. He doubts a company can command a significantly higher price for the prescription version.

For Indena, selling plant-derived nutritional supplements by prescription revives a business model the firm undertook in the 1960s when it was known as Inverni Della Beffa and sold prescription pharmaceuticals. The pharmaceutical business was sold in the mid-1990s to Synthelabo, now part of Sanofi-Aventis. The name Indena—short for Industria Derivati Naturali—came into use in the mid-1980s to identify the extracts and API businesses.

IDB Holdings, Indena’s parent, recently reacquired the Inverni Della Beffa name. In Italy, “it’s a souvenir brand” that will provide traction in the nutritional supplement business, Bonacorsi tells C&EN. He says Indena has done the research needed to back the diet aid. “You need strong evidence to sell this way,” he notes.

Although the supplement product line is important, Bonacorsi says Indena’s future will be increasingly dependent on its own new ethical pharmaceutical discoveries.

In a moment of optimism, Bonacorsi predicts that success with such products could double Indena sales in five years. But then he recalls the ebbs and flows the firm has seen in the past and moderates his outlook. “The world is changing so quickly,” Bonacorsi says, “we would be happy with 10% annual growth.”

 
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