West Coast Editor
CombinatoRx Inc.'s low-dose pairing of prednisolone and dipyridamole, CRx-102, proved positive in preliminary data from a Phase II trial that tested the compound in patients with osteoarthritis of the hand - the first time one of the firm's combo drugs has hit statistical significance.
"It's a big deal for us, because all of the products in our portfolio are home grown," said Alexis Borisy, president and CEO of Boston-based CombinatoRx. The company's stock (NASDAQ:CRXX) closed Monday at $12.48, up $1.87, or 12.6 percent.
Comparing CRx-102 to placebo, the six-week trial's primary endpoint was pain relief in subjects with hand osteoarthritis, as measured by the AUSCAN pain subscale index. AUSCAN stands for the Australian-Canadian Scale for Hand Osteoarthritis, a visual analogue scale developed specifically for the condition.
Analysis showed the mean change from baseline in the CRx-102 group was -102.4 mm (a 33 percent improvement in pain) compared to the mean change from baseline in the placebo group of -30.9 mm (a 10 percent improvement), thus reaching a statistically significant outcome (p=0.0006).
CRx-102 was generally well tolerated with no serious adverse events. The most common adverse events were headache and nausea, which are known side effects of one of the two components that make up the drug.
Secondary endpoints include the patient's global assessment, the AUSCAN physical function subscale, pain relief of joints of the hand and biomarkers.
At four Norwegian study centers, 83 subjects were enrolled who had moderate to severe hand osteoarthritis as determined by American College of Rheumatology criteria and a minimum score on the AUSCAN scale. CRx-102 was dosed using 3 mg of prednisolone and two different doses of dipyridamole, with patients getting the first ratio for the initial week of treatment, and the second ratio for the following five weeks.
"We're finding special pairs [of drugs] that you could never have found a priori," Borisy said, noting that the average researcher would not have considered putting a low-dose steroid (so low that it's considered "sub-active") with an anti-platelet drug for osteoarthritis and other indications.
High-throughput screening and other technologies come into play, he said.
"This is not as simple as putting an asthma drug with an asthma drug to make another asthma drug," Borisy said. "They have to be at the right place at the right time to get this synergistic effect. We have to adjust the pharmaceutical property so they are aligned appropriately."
The result is a new drug that is not substitutable by generics, which is strongly protected by patent, working by a unique mechanism of action.
Two other Phase II trials with CRx-102 are under way, one in rheumatoid arthritis and another in a systemic inflammatory disease model of chronic adult periodontitis. The compound is one in a portfolio of seven at the Phase II level, and Borisy said CombinatoRx expects to report data from 11 Phase II trials this year.
CRx-102 is not partnered but probably will be, given the size of the markets targeted.
"Certainly with the resources the company has today, you would have to make that assumption," Borisy told BioWorld Today. "We can afford to do the Phase IIb [trials] ourselves," but likely would seek a partner for certain compounds before Phase III or shortly after starting trials.
"It's very hard to make predictions" about which of the drugs might be partnered in which indications, he added, calling the chances "very unlikely that all of them will succeed, and very unlikely that all of them would fail." If "five or six come back with fantastic data," the company could not proceed with all of them without partners, he said.
"Some we will retain all the way to market, and others we will partner after the clinical value has been established," Borisy said. Although "where that value explodes depends on the product," a deal involving a small royalty stream is "not what investors care about in the long run," and CombinatoRx can afford to wait for clinical proof.
Alex Hittle, analyst with A.G. Edwards in St. Louis, initiated coverage in mid-January with a "buy" rating, and wrote in a research note at the time that "if at least two or three" of CombinatoRx's Phase II compounds show strong enough data to justify Phase IIb trials, then "market perceptions of [the firm] could change from its current platform company with a pipeline' to a pipeline company with a platform.' In the meantime, the company has about $113 million heading into 2006, which we believe could carry the company at least two years before it needs to raise additional capital."
CombinatoRx, which went public in November, raising $42 million, has made deals worth a total potential of about $600 million over the past year, including a multiyear research and licensing agreement last fall with Vancouver, British Columbia-based Angiotech Pharmaceuticals Inc. valued at up to $500 million. (See BioWorld Today, Nov. 10, 2005, and Oct. 5, 2005.)
The Angiotech deal includes a $27 million up-front license payment, as well as a $15 million equity investment, entitling Angiotech to license up to 10 CombinatoRx compounds.