to be safe in their existing forms for years, which is a feature that Montgomery has sought out before in drug candidates as he tries to reduce the risk of unexpected side effects popping up in development. The plan here is to combine the two antibiotics in an aerosol form, give them in about one-tenth the usual dose, but deliver it where it needs to go deep in the lungs with a nebulizer that’s modified to work with mechanical ventilators, Montgomery says. The nebulizer that Cardeas is using is a modified form of the Pari e-Flow device that Montgomery and his team used before to develop aztreonam lysine (Cayston) to fight lung infections in cystic fibrosis patients.
While getting into the lungs to fight infections is desirable, Cardeas doesn’t expect its drug will be the silver bullet for ventilator-associated pneumonias. The Cardeas drugs will likely be given in combination with intravenous antibiotics that circulate throughout the bloodstream, which have a better chance of killing infectious bugs outside the lungs, Montgomery says.
So far, Cardeas has found its combination is safe in animals and kills all the nasty bugs it intends to kill in the petri dish. It has done much of that early spade work—formulation, toxicology testing—with a lean team of just six people and a network of contractors, Montgomery says. “When you’re doing a virtual company, you really need experienced people. It’s taken us six months to do what it took Corus Pharma (his previous startup) 19 months to do,” Montgomery says.
The next step is to run an initial clinical trial in 16 patients in hospital ICUs at a single site in Australia, where Montgomery says it is easier to get through regulatory steps to get the study up and running. Since ventilator-associated pneumonia is a short-term illness, the trial only needs to look at how patients do on 10 days of therapy, and doesn’t require long-term follow-up. While the main goal of this initial phase study will be to assess safety and tolerability, Cardeas will also be able to measure how much of its antibiotics are getting into sputum secretions from the lungs, which offers a hint of whether the drug has a good chance of clearing future efficacy hurdles.
One competing product, from Bayer and Nektar Therapeutics, is an aerosol form of amikacin for ventilator-associated pneumonia, Montgomery says. But that approach is limited, he says, because amikacin only works against gram-negative bugs, not MRSA. Bayer touted the program at a medical meeting in May 2008, but hasn’t said much publicly about this program since that I could find. Nektar lists the product on its website as in Phase II development. “It’s good, but not good enough,” Montgomery says. “They did a Phase II study about four or five years ago. I’ve heard they are trying to get the delivery system fixed.”
These are still clearly early days at Cardeas, and a lot of work will need to be done to figure out what kind of proof the company will need from Phase II and Phase III clinical trials to pass muster with FDA and European Union regulators. But even though it’s still years from getting that far, much less into negotiations with health insurers over reimbursement, Montgomery says he’s picked this program partly because it shouldn’t have a problem getting paid for it.
Essentially, when health economic studies say the condition costs $40,000 or more per episode and an extra seven to nine days in the hospital, a new drug that reduces the time people spend in the hospital would be valuable, because it prevents a lot of those bad things that are bound to happen when people stay too long.
“If this thing does become the standard of care in intensive care units, then there are a lot of patients out there to treat. And even if you price it so the hospital gets a significant return on investment, it’s still a billion-dollar drug,” Montgomery says.
