CombinatoRx is coming to one of those defining moments where it will either vault into becoming an emerging biotech industry player or it will take a big leap backwards. The Cambridge, MA-based company (NASDAQ: CRXX) will find out within the next four weeks whether its experimental combination drug for arthritis is likely to become a multi-billion dollar product, or a big, fat zero.
If a clinical trial of Synavive succeeds, “it certainly would mean we would pop the champagne,” says Gina Nugent, the company’s vice president of investor relations. If not, “it wouldn’t really be a clean-out-your-desks moment, but it may be that you’d have to take a shot of tequila. Maybe cry a little,” she says.
CombinatoRx was founded back in March 2000, has no marketed products, and has spent $220 million through the end of June on building a pipeline of drug candidates—so this first major clinical trial counts for a lot. The company’s medicines are unusual, because instead of developing new drugs from scratch, it uses computer screening methods to find novel treatments that combine conventional pharmaceuticals in new ways to improve their effectiveness. Its lead candidate at the moment is Synavive for osteoarthritis, the painful joint disease that affects an estimated 20 million people in the U.S., according to the National Institutes of Health. This is the form of arthritis traditionally associated with old age, degeneration of the joints, and for which people still mostly take over-the-counter pain meds, or possibly Pfizer’s Celebrex.
Synavive is designed to take a common generic immune-suppressor, prednisolone, in a very low dose, and combine it with dipyridamole, an anti-blood clotting agent. The idea is that by going to a low dose of the immune suppressor, patients can avoid some of its nasty side effects, like increased risk of osteoporosis and cataracts, while the dipyridamole activates it in such a way that it retains its full anti-inflammatory pain relief action.
The drug is currently in a 279-patient clinical trial of patients with arthritic knees, called Comet-1, says John Randle, the company’s senior vice president of corporate development. The main goal is to show improved pain relief compared with a placebo after three months of treatment, with a secondary goal of showing the combination is better than just plain low-dose prednisolone by itself. Results are expected in October, Randle says.
CombinatoRx was encouraged to go this far by earlier trials. One suggested its combo could help almost two-thirds of patients achieve a 20- percent reduction in symptoms of rheumatoid arthritis after six weeks, compared with about one-third who did that well on placebo. Another study of patients with osteoarthritis in the hands found that patients on Synavive had a 31 percent average reduction in pain, compare with 7 percent on a placebo.
There was a catch here, though, with patients complaining of headaches in the earlier trials. About half of patients had headaches, and about one fourth dropped out of the earlier studies, Randle says. That problem has been addressed by changing the trial design to allow the drug to be taken with food, and allowing an over-the-counter pain med in the ongoing study for headaches. A new formulation of the drug is designed to slow down the absorption of dipyridamole, to stop it from causing headaches, Randle says. The dropout rate in the ongoing study has fallen considerably, he says.
Another change: dosing. Earlier studies required that patients take multiple pills of prednisolone and dipyridamole twice daily, while the ongoing Comet-1 study combines them into a single capsule that is taken twice daily. The company is now working on another formula for a capsule that could allow the medicine to be taken once daily. CombinatoRx CEO Alexis Borisy (an Xconomist) likes to call these various formulations “Good, Better, and Best,” says Nugent.
If the Comet trial succeeds in October, then CombinatoRx will rev up talks with big drugmaker partners who can help it run the pivotal clinical trials needed to get Synavive approved by the FDA, Randle says. CombinatoRx, with just 160 employees, doesn’t have the capital or human resources to run such trials, which require thousands of patients to demonstrate safety. The partner will also have to have marketing muscle, and an interest in extending Synavive’s reach to patients with rheumatoid arthritis, asthma, and chronic obstructive pulmonary disease, Nugent says. Pricing of the drug will probably be similar to the Cox-2 inhibitors, like Celebrex, at about $1,500 to $1,800 a year, per patient, Randle says.
One irritating aspect of this trial is the timing. The results are coming out past the deadline for the American College of Rheumatology meeting in San Francisco, and the next big meeting on the calendar where CombinatoRx wants to present the data is The European League Against Rheumatism, which isn’t coming until June. So that means that CombinatoRx could release some of the basic results in a press release to investors in October, but we may all have to wait nine months for the full details to come out in public. I guess we’ll have to speculate how good the data really is by reading between the lines in the coming months, if and when a big drugmaker writes CombinatoRx a big check for a piece of Synavive.
If Synavive flames out, then CombinatoRx will have to turn to three other drugs in early-stage clinical trials for dermatology conditions and diabetes. Not all biotechs have that many fallback options, so life will go on at CombinatoRx. But like Nugent says, it would certainly give investors, employees, and patients a reason to down a tequila shot or two.