Lpath Inc., a small biotech based in San Diego, saw its shares tumble in heavy trading following the release of news that its phase IIa single-agent, open-label study of Asonep, an anti-sphingosine-1-phosphate (S1P) antibody formulated for systemic administration, did not meet the primary endpoint of statistically significant progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC).

The PFS significance hinged on at least 25 out of 39 patients needing to be progression-free at two months of treatment. However, only 15 patients achieved PFS past two months, explained Dario Paggiarino, chief development officer of Lpath, in an investor update conference call.

The overall median time to progression was less than two months.

The study involved RCC patients who had previously failed treatment with at least one anti-VEGF agent such as Sutent (sunitinib, Pfizer Inc.) and no more than one mTOR inhibitor such as Afinitor (everolimus, Novartis AG). That patient population is considered to be "last line," with cancer progression extremely rapid within a one- to two-month time frame.

If patients did manage to be progression-free past two months, they remained so for a considerable period, explained Paggiarino. Seven patients, in fact, were progression-free for at least six months, with three patients progression-free for more than 20 months. Six patients from the trial currently continue to receive weekly infusions of Asonep.

While the study was not successful in that cancer indication, S1P has been implicated in cancer progression, which is why the company has analyzed the expression profile of the S1P pathway from a genetic database of thousands of cancer patient genomes with the goal that "there could be a rationale for Asonep in other cancer types where S1P pathway dysregulation suggests a stronger pharmacological rationale," said Paggiarino.

The company said it plans to explore those other opportunities with a potential partner when the RCC trial ends.

Lpath does have other shots on goal, which is one of the reasons the Aronsep trial miss was probably less dramatic on the company's share value than it could have been.

While Asonsep is a systemic formulation of a humanized antibody designed to bind and neutralize the bioactive lipid, S1P, the company is also developing an ocular formulation of sonepcizumab, Isonep, which was also discovered using its ImmuneY2 drug-discovery engine that generates therapeutic antibodies that bind to and inhibit bioactive lipids that contribute to disease.

Isonep is being investigated in a phase II trial (designated Nexus) in patients with wet age-related macular degeneration (wet AMD).

In December, enrollment was completed. The multicenter trial included wet AMD patients who have not responded well to existing anti-VEGF therapies, including Lucentis (ranibizumab, Roche AG), Avastin (bevacizumab, Roche AG) and Eylea (aflibercept, Regeneron Pharmaceuticals Inc./Bayer AG). The primary endpoint of the Nexus study is a mean change in best corrected visual acuity (BCVA) at 120 days. Secondary endpoints include measurements of retinal thickness, neovascular lesion size and safety, among others

In 2010, Lpath entered an agreement with Pfizer Inc. providing the New York-based big pharma with an exclusive option for a worldwide license to develop and commercialize Isonep.

According to Paggiarino, the top-line study results are expected to be available in the second quarter.

The company's shares (NASDAQ:LPTN) closed Wednesday at $2.52, down 23 percent.