It’s been more than four decades since a new drug for tuberculosis has been approved by the FDA. Although Janssen is igniting hope with bedaquiline, which has been given priority review by the FDA and is set to begin late-stage trials this fall, there is still a great need for new ways to prevent and treat the disease.
Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis, now part of the TB lexicon, have developed from misuse of antibiotics, especially in emerging markets like India, China, South Africa and Russia. The TB community is crying out for treatments that are stable, easier to take than the current drug regimen, and can be used along with HIV drugs.
With that in mind, a humble Indiana startup is hoping to deliver a stable, oral drug that’s dosed once a day or less to help prevent patients from developing those drug-resistant forms.
“TB is unique – it actually hides inside cells of the immune system,” said Francis Burrows, the company’s chief scientific officer. “Once the body recognizes it, (TB) allows itself to be engulfed by immune cells, but it has all these mechanisms that it uses to survive inside the macrophage, like a parasite.”
That’s why treatment requires a cocktail of drugs taken for six to nine months, and why it’s so dangerous when patients don’t follow through with the entire course of treatment. “Within two to three weeks, the antibiotics have killed most of the bacteria in the body,” he said. “You start to feel fine, so you stop taking them, but you don’t realize there’s still a little bit left. Six months later, you have TB again, but it increases the chances it’s resistant to the drug.”
Aarden’s approach, according to Burrows, blocks several of the methods TB bacteria use to hide inside cells. That’s important because antibiotics don’t do a good job of getting to those, and they’re the ones that come back and cause a relapse, Burrows said. “Our method is inactive against those floating in blood, but we think if we add it to current drugs, people won’t relapse and develop the resistant form.”
In a study supported by the National Institute of Allergy and Infectious Diseases, Aarden tested the drug in guinea pigs, in combination with Isoniazid, the first-in-line medication in the treatment of tuberculosis. In the study, the time it took to eradicate the infection was half the time it took using Isoniazid alone, according to CEO Gary Noonan.
Despite the promising results, it’s still early in the testing process, and there’s a lot of work that needs to be done even before the drug is tried in humans. The next step is to advance the candidate into more elaborate toxicology studies, which, if all goes well, would enable the company to prepare and submit an IND to begin human trials.
In order to get there, though, it needs a partner to help with manufacturing and testing. Fortunately for Aarden, there are plenty of potential partners. GlaxoSmithKline, Novartis, AstraZeneca, Eli Lilly, Otsuka and Sanofi-Aventis are just a few of the pharmaceutical companies that have made public their tuberculosis programs. “China and India also have flourishing pharmaceutical industries themselves, so they have a strong interest in TB,” Burrows noted. And because it’s considered a public health issue, there’s a lot of financial support for these drug from governments worldwide, he added.
In fact, as the company has fought to get across the biotech valley of death, its savior has come in the form of government funding. “If you wanted a knight in shining armor for this valley of death, the NIAID really fills that role,” Burrows said. Aarden has also received funding from the Indiana Economic Development Corporation’s 21st Century Research and Technology Fund, BioCrossroads’ seed fund and private investors.
The last time we talked with him, Noonan said he had hoped to have a drug ready for IND-enabling studies by the end of 2011. That goal, he admits, may have been a little aggressive for the small biotech startup. “The last three years have been very difficult,” he said.
Now, the company’s timeline depends on its ability to find a partner. “The industry standard from when one initiates IND-enabling work to when it files is usually 12-18 months, but now our timeline on this is not our own – it’s the timeline of whoever we partner with,” Noonan said.
Meanwhile, Aarden is continuing work on two other programs, one in oncology and the other in autoimmune disease.
[Photo from Wikimedia Commons]
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