Opko Health Inc. - the result of a recent three-way merger involving Acuity Pharmaceuticals Inc., Froptix Corp. and eXegenics Inc. - initiated a Phase III trial of siRNA drug bevasiranib in wet age-related macular degeneration (wet AMD).
Sam Reich, executive vice president of ophthalmology at Miami-based Opko, likened the trial design to fixing a leaky basement. All patients will receive initial pre-treatment with three injections of Lucentis (ranibizumab, Genentech Inc.), which "mops the water off the floor" by antagonizing existing vascular endothelial growth factor (VEGF), he said. Patients then will be randomized to treatment with Lucentis every four weeks, bevasiranib every eight weeks or bevasiranib every 12 weeks.
By using siRNA to prevent production of VEGF, the hope is that bevasiranib will "repair the leak," Reich said.
Enrollment in the 330-patient trial, known as COBALT (Combining Bevasiranib And Lucentis Therapy), is expected to take about 12 months. The study will continue for two years, although data on the primary endpoint of non-inferiority in visual acuity compared to Lucentis are expected after one year, or around mid-2009.
Reich noted that the trial is designed so that "if [bevasiranib] were to be superior, that would be shown," although the drug could be commercialized based on equivalent efficacy to Lucentis.
Aside from its potentially complementary mechanism of action, bevasiranib has the lure of less-frequent injections, which may resonate with the elderly and often less-mobile wet AMD patient population.
Lucentis has dominated the wet AMD market since its mid-2006 launch, generating $211 million in the first quarter and marginalizing many of its competitors. OSI Pharmaceutical Inc. is planning to divest its eye disease business, including its VEGF inhibitor for wet AMD, Macugen (pegaptanib sodium), which earned $103 million in 2006. Visudyne (verteporfin), the wet AMD drug from QLT Inc. and Novartis AG, managed $61.2 million in global sales in the first quarter of 2007, a 42.7 percent decrease from the same quarter in 2006. And Genaera Corp. discontinued development of its wet AMD drug Evizon (squalamine lactate) after Lucentis's launch.
Opko isn't the only company to think an RNAi approach to wet AMD might be able to grab significant market share. Allergan Inc. is conducting a Phase II wet AMD trial with the siRNA drug AGN211745 (previously known as Sirna-027), while Pfizer Inc. is conducting a Phase I/II wet AMD trial with an RNAi drug licensed from Quark Biotech Inc. and Silence Therapeutics plc. Another company not giving up on wet AMD is Regeneron Pharmaceuticals Inc., which is gearing up to start a Phase III trial with partner Bayer Healthcare AG using its VEGF trap approach.
As data from Opko's Phase III trial become available, Reich said the company may be "open" to considering a partnership. "I think we'll have plenty of opportunities," he added.
If recent activity in the RNAi space is any indication, Opko should have no shortage of suitors. Earlier this month, Alnylam Pharmaceuticals Inc. signed a potential $1 billion nonexclusive RNAi deal with Roche Holding AG, and Silence inked a potential $403 million RNAi deal with AstraZeneca plc. And who can forget Sirna Therapeutics Inc.'s $1.1 billion take-out by Merck & Co. Inc.? (See BioWorld Today, Nov. 1, 2006, July 9, 2007, and July 10, 2007.)
Investors as well as partners seem to be keen on RNAi. Last month, Cequent Pharmaceuticals Corp. closed a $9 million Series A financing to support its Transkingdom RNAi work. Earlier in the year, CytRx Corp. raised $37 million in a PIPE, nearly half of which will go to its RNAi subsidiary, RXi Pharmaceuticals Corp. (See BioWorld Today, April 19, 2007, and June 27, 2007.)
Shares of Miami-based Opko (AMEX:OPK) rose 5.4 percent, or 18 cents, to close at $3.54 Wednesday.
Although bevasiranib is Opko's lead product, privately held Acuity and Froptix provided several other preclinical and clinical programs for ophthalmic indications such as dry AMD and retinitis pigmentosa, as well as complementary diagnostic products. EXegenics served as a shell, providing access to public markets and $16 million in cash. (See BioWorld Today, March 28, 2007.)
Reich said Opko also has considered the applicability of bevasiranib in oncology, looking at both local and systemic delivery options. Yet he doesn't anticipate facing the pricing issues Genentech has dealt with around Lucentis and its less expensive cousin, the cancer drug Avastin (bevacizumab).
"We see Avastin and Lucentis as similar to each other while bevasiranib is a significant step forward," he said.