Coming up with drugs that belong on the radar - and prescription pads - of primary-care doctors is "a challenge that biotech is treading carefully on," as Peter Hecht, CEO of Microbia Inc., told BioWorld Financial Watch last week, but Hecht's firm made a major footfall into the zone with its potential $330 million deal with Forest Laboratories Inc.
The targeted indication is a tricky one: irritable bowel syndrome (IBS), which accounts for 12 percent of adult visits to doctors, and is the most common disorder diagnosed by gastroenterologists. Costs associated with the complaint surpass $25 billion every year, and IBS patients fall into three subgroups: constipation-predominant (IBS-C), diarrhea-predominant (IBS-D) and alternating (IBS-A). By far the most common type is IBS-C, which afflicts 30 percent to 40 percent of all patients, making up a market pool of about 9 million.
IBS-C is the target, along with chronic constipation, of linaclotide, a 14-amino-acid peptide undergoing Phase IIb trials that are expected to enroll about 700 patients, with 400 in IBS and the remainder in chronic constipation. Microbia expects to offer data from the trials in the first half of next year. If they are favorable, Phase III studies would begin in the second half. "They will be separate Phase III programs, running in parallel," Hecht said. "For each [indication], we'll need a pair of studies."
Although Microbia has been working on the indication for much longer, companies with strong candidates for IBS-C began drawing particular interest from investors earlier this year, when Novartis AG withdrew Zelnorm (tegaserod) because of concerns regarding possible cardiovascular side effects.
"I think it's been clear for a long time, the number of patients unsatisfied with current therapies," Hecht said, and the eager acceptance of Zelnorm before problems arose was an indicator.
Other companies with IBS-C programs in the works include Sucampo Pharmaceuticals Inc., which also had news last week, saying that the FDA accepted its supplemental new drug application for lubiprostone, a chloride channel activator already approved under the brand name Amitiza for chronic idiopathic constipation - the only such prescription drug approved by the FDA. Phase III trials are testing the compound in opioid-induced bowel dysfunction, as well.
Ryuji Ueno, Sucampo's chairman and CEO, pointed out that Microbia's research so far has been "very small scale. We're not confident whether [linaclotide] can be a candidate." Twice-daily Amitiza, though, can cause nausea, a side effect Hecht said has not shown up with linaclotide, a once-per-day capsule.
Determining what is IBS and what's not is "problematic," said Brad Fackler, vice president of commercial operations for Sucampo. "It's not like blood pressure. There's no quantitative diagnostic test for this."
Therapies invented until now have targeted serotonin in various ways and were designed to work against diarrheic IBS, Hecht said.
Another company's IBS work to make headlines last week: Ocera Therapeutics Inc., which started a Phase II trial with AST-120, an oral adsorbent compound, at four centers in Belgium in patients with non-constipating IBS. Already used in more than 200,000 patients in Japan, the compound also is being tried in a pivotal Phase III study in fistulizing Crohn's disease in North America and Europe. The drug absorbs toxins and mediators of inflammation from the gastrointestinal tract, preventing local toxicity and systemic absorption.
Microbia's linaclotide, also limited to the lining of the intestine, acts as an agonist of the guanylate cyclase type-C receptor - a "completely different mechanism than any current or previous therapy," Hecht noted.
Under the terms of the Forest deal, Microbia is getting $125 million of the possible $330 in the near term, Hecht said, and the $125 million includes an immediate $70 million license fee. The two firms will split U.S. development and marketing costs as well as profits, and Microbia stands to get royalties from sales in Mexico and Canada, where Forest holds exclusive rights.
Of biotech deals involving primary-care products, "there are so few examples," Hecht said, "really only a handful." He cited Amylin Pharmaceuticals Inc. and Eli Lilly and Co., which brought the world Byetta (exenatide), an injectable for Type II diabetes that sold $152.1 million in the second quarter of this year. It was approved in the spring of 2005. Lilly also was the partner for Cialis (tadalifil), the erectile dysfunction drug developed through a joint venture with ICOS Corp., which Lilly bought in the fall of last year for $2.1 billion.
"Now Sepracor is trying with Lunesta, and Forest has a bunch of primary care products - but that's it," Hecht said. Earlier this month, Sepracor Inc. entered a potential $155 million deal with GlaxoSmithKline plc covering the insomnia drug Lunesta (eszopiclone) in Europe and elsewhere. Sepracor gets $20 million up front and up to $135 million more in potential milestone payments, as well as escalating double-digit royalties on resulting sales.
Microbia's officials, Hecht said, tried to learn and take the best from each of the agreements they studied. "We think we have it right with this deal," he said.
The arrangement brings another, critical benefit, enabling Microbia's longer-term strategy, he said. "Together with the equity we've raised [since inception] - $230 million from some super private and public investors - we can cover our portion of the costs of the drug, invest in building U.S. commercial capability, and invest in the pipeline," Hecht said. "We have a number of things coming behind [linaclotide] in pain, asthma and so on."