First Tuberculosis Drug in 40 Years Has Otsuka Cautious

Stalling Sales May Give Otsuka Edge With Cure for TB Superbugs
Otsuka is best known in the pharmaceutical industry as the developer of one of the world’s bestselling treatments for schizophrenia, Abilify. Photographer: Tomohiro Ohsumi/Bloomberg

Otsuka Holdings Co. executives are drawing up plans to ensure their new drug isn’t a quick hit.

The Japanese company says it’s proceeding with caution now that the medicine, which may be the first new tuberculosis treatment in four decades, passed a key test.

A study published in the New England Journal of Medicine today shows Otsuka’s delamanid helped fight tuberculosis strains not stopped by other medications. The Tokyo-based drugmaker, which began seeking treatments for the deadly lung disease in 1982, says it’s drawing up plans to restrict access to select physicians to avoid the bug building resistance.

“We’ve invested a lot of time and money to develop this drug, but we are not seeking robust sales growth immediately,” Masuhiro Yoshitake, Otsuka’s head of tuberculosis projects, said in an interview. “We want to begin selling to people who know how to use the drug.”

Doctors must balance the need to fight hard-to-treat cases against prolonging the medicine’s potency. Taking measures to control delamanid’s use would avoid spoiling the first new promising weapon against TB in 40 years, said Marc Pellegrini, an infectious diseases physician and TB researcher at Melbourne’s Walter & Eliza Hall Institute of Medical Research.

“It’s refreshing to see a drug company actually promote that over and above widespread use,” said Pellegrini, who wasn’t involved in the delamanid study. “It shows that there are still companies that are altruistic enough to find TB medications, which we desperately need.”

Sputum Test

About 1.4 million people died from TB in 2010, making the airborne bacteria the second-biggest global killer after HIV and AIDS, according to the World Health Organization.

The bug has developed genetic mutations that enable it to evade drugs or linger longer in the respiratory tract. A new strain in four patients in India appeared to resist all known antibiotics, the medical journal Clinical Infectious Diseases reported in December.

The drug probably won’t become a blockbuster, especially because to preserve its potency it will only be available to people with a form of TB that shows resistance to other medicines, analysts say. It may generate about 10 billion yen ($127 million) a year in sales in Europe, the U.S. and Japan at its peak, said Fumiyoshi Sakai of Credit Suisse AG in Tokyo.

The study released today showed that 45.4 percent of patients taking delamanid in combination with standard therapy for multidrug-resistant TB infection no longer had the bacteria in their sputum after two months, compared with 29.6 percent of patients taking the usual medicines plus a placebo.

Explosive Drug

“The findings in this paper are exciting,” said Bernadette Saunders, a scientist in the Mycobacterial Research Division of Sydney’s Centenary Institute. “It shows a new antibiotic that can successfully kill multidrug-resistant strains of TB.”

Otsuka is best known in the pharmaceutical industry as the developer of one of the world’s bestselling treatments for schizophrenia, Abilify. The family-owned company began operating in 1921 by making chemicals near the city of Naruto. It first sold shares to the public in 2010.

The stock rose 0.8 percent to 2,461 yen in Tokyo trading today. Otsuka shares have gained 14 percent this year, the fourth-best performer on the Topix Pharmaceutical Index, which fell 1 percent for the period.

The scientist who developed the medicine took risks to find a way to mass produce it because its active ingredient is derived from an explosive and could have detonated in the factory, and postponed retirement to follow the project, according to a 2009 interview.

Dire Need

Delamanid works by blocking the production of mycolic acid, a key component of the dense, waxy shell that encases the tuberculosis bug and helps it resist penicillin and most antibiotics. It has completed the second of three research stages required for marketing approval. Because there is a dire need for new TB drugs, regulators may allow the company to skip the last level of tests, and Otsuka says it’s already filed for clearance to sell it in Europe. It’s in talks with regulators in the U.S. and Japan.

Johnson & Johnson and the TB Alliance, a New York-based non-profit group supported by the Bill and Melinda Gates and Rockefeller Foundations, are also developing new TB medicines.

The crucial question is “how these drugs are going to be used,” Daniel Chin, TB program officer for the Gates Foundation in Beijing, said in a telephone interview. The concern is that “as soon as they are introduced we are going to lose them to drug resistance.”

Cautious Approach

Otsuka says it’s aware of the risk and wants to be “part of a sustainable model for TB,” according to Yoshitake. He said the Japanese drugmaker feels “pressure to handle this project carefully,” even though it will cost the company more.

That may mean not using the medicine in isolation in patients with the active form of TB, said Justin Denholm, an infectious diseases epidemiologist at the Royal Melbourne Hospital, who is studying transmission patterns in Australia’s Victoria state.

“It’s critically important that a new class of antibiotic is well defended and is always accompanied by other medications that are effective for treating the specific strain of TB,” said Denholm. “I am really encouraged to hear that response from the company. It’s a nice and often-lacking sign of good corporate stewardship.”

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