BioWorld Today Correspondent

Shares in Santhera Pharmaceuticals AG gained almost 11 percent Wednesday on news that the company plans to file for approval early next year for idebenone (Catena) in Leber's hereditary optical neuropathy (LHON), following a Phase II trial, which indicated that it improves vision in patients.

The study was conducted in centers in the UK, Germany and Canada. But Liestal, Switzerland-based Santhera aims to file for approval in both Europe and the U.S. on the strength of the data.

"In the course of the summer, we will not only want to meet with the CHMP but also the FDA," Chief Scientific Officer Thomas Meier told BioWorld Today.

If it obtains fast-track designation in the U.S., it could potentially reach the market before year-end, said CEO Klaus Schollmeier, whereas the European approval process would take about 10 to 11 months.

As yet, the product is unpartnered. The company's strategy all along has been to commercialize the product in the U.S., and to seek a partner for Europe and the rest of the world. "At the moment I see no reason to change this," Schollmeier said.

The so-called RHODOS (Rescue of Hereditary Optic Disease Outpatient Study) trial was the first-ever randomized, placebo-controlled study in LHON, a hereditary disease that can lead to loss of central vision in young adults and, ultimately, blindness.

It is caused by mutations in genes encoding the enzymes the comprise Complex I, the first component of the electron transport chain in mitochondria.

The study was originally designed to assess the efficacy of the drug in newly diagnosed patients at high risk of vision loss. However, because of recruitment difficulties arising from the paucity of patients in this category, the protocol was adapted to include those with advanced disease as well.

In the intent-to-treat analysis (n = 82), the drug failed to reach statistical significance on its primary endpoint, "best recovery" (p = 0.291), or on a key secondary endpoint, "best acuity" (p = 0.078). However, company officials were upbeat on the overall data package, which clearly differentiated Catena from placebo.

Moreover, according to scientific advice and protocol assistance it received from the British Medicines and Healthcare Regulatory Agency and the European Medicines Agency's Committee for Medicinal Products for Human Use, respectively, a "standard interpretation" of p-values may not be required to demonstrate that the drug offers a positive risk-benefit profile in this indication.

Best acuity will be the key measure on which the drug's efficacy will be assessed, as it provides a measure of a patient's overall ability to see. Best recovery, which refers to an improvement in either eye, "does not necessarily result in best vision for the patient," Meier said. That's because a large improvement in the more severely affected eye may not contribute to an overall improvement in vision.

In the intent-to-treat analysis of the best acuity measure, patients who received the drug (n = 53) were able to read five more letters on a standard ophthalmology chart than those on placebo (n = 29).

The gap consisted of a one-letter improvement in the treatment group and a four-letter deterioration in the control group.

On the best recovery measure, the difference was three letters. On a third endpoint, "acuity in both eyes," which measures both eyes together, the improvement of drug over placebo was four letters (p = 0.026).

"We have in this study two populations," Schollmeier said. "What you see in these endpoints is a blend of both," he added. "They are all consistent and all point in the same direction," Meier said.

Catena did attain statistical significance - and higher levels of efficacy - in subgroup analyses of patients who were legally blind and of patients at highest risk of vision loss.

"It's clear that patients at highest risk responded the best to Catena," Meier said on an analyst conference call. Further subgroup analyses are ongoing.

Santhera's stock (ZURICH:SANN) closed Wednesday at CHF8.96 (US$7.95), up CHF0.88.

The company's share price has plummeted since Catena missed the primary endpoint of a Phase III trial in Friedreich's ataxia. It is now valued at just under CHF28 million, little more than half the CHF53.3 million in cash it reported at the end of 2009.