Dual-filing feat a rarity for little guy

February 17, 2010 – 2:18 pm by Michael Christel

You may have read recently about a small biotech outfit in New Jersey having successfully submitted simultaneous regulatory filings in the United States and Europe for Luveniq, a new oral treatment for non-infectious uveitis, an inflammatory condition of the eye that can lead to blindness (see the release here). You may have also wondered how a company of this size – in this case, Lux Biosciences and its staff of 22 – was able to pull off such a feat, especially given the still-sputtering biotech-funding market and the traditionally resource-challenged environment for small biotechs.

Curious myself, I caught up with Lux’s president and CEO, Dr. Ulrich Grau, to find out more about the dual-filing achievement. While the R&D veteran told me Lux has received about $100 million from venture capital investors since he helped found the company in 2006, what was apparent from our conversation is the complex scope of the Luveniq program, from preparing the new drug applications to current execution and timeline commitments with FDA and EMA during the review process.

Check out these numbers for proof:

• While about 80% of the U.S. and European dossiers were overlapping and could be cloned, 20% were not.

“There’s actually still quite a bit of work that goes into that 20%,â€� Dr. Grau says.

• Luveniq was a full submission, with chemistry, manufacturing & controls information and non-clinical and clinical data included. Total size of file: 20 gigabytes.

“If you had to print it out, which obviously we don’t, it was around a million pages,� Dr. Grau tells me. “So that was a large submission by any measure.�

Including that of e-submission vendor Octagon Research Solutions, which worked with Lux on the assembly and publishing activities associated with the filing. According to Dr. Grau, Octagon’s average file size for new drug applications typically ranges between 10 and 20 gigabytes.

• Lux has collected promising data from 450 patients at 56 sites in seven countries since launching the Luveniq uveitis clinical program in 2007. The drug’s mechanism, voclosporin, is also being studied in psoriasis by Lux’s partner Isotechnika Inc., which originally developed the molecule and licensed it to Lux for ophthalmic use in 2006.

U.S. and European regulators allowed Lux to include psoriasis data in its submission materials for the unveitis indication, giving the company a safety database of 2,110 subjects. Luveniq, an oral calcineurin inhibitor, has orphan-drug designations from FDA and EMA and fast-track status from FDA. Lux has also requested priority review from FDA.

“It’s a challenge for a small organization like ours to orchestrate that properly,� Dr Grau says of the simultaneous submissions. “We’re working in a semi-virtual environment whereby we have 22 employees inside the company and we develop from a large network of consultants and advisors and contractors. We had also support and significant contributions from our partner Isotechnika. All the preclinical work at the time was done by Isotechnika.�

• Lux now faces a daunting series of timeline milestones in the coming months as regulators evaluate Luveniq. According to Dr. Grau, the U.S. program includes reviews at days 45, 74, and 120, while in Europe, there are reviews at days 80 and 120.

“I needed to look downstream and see whether as a small team, can we handle all the questions when they come in, rather than just be able to answer, let’s say, FDA questions and not having the time and resource to work on EMA questions,� Dr. Grau says. “Overall, if you sketch it out, it is a tense schedule. But by the same token, I’m pretty confident that we’ll be able to handle it.�

Lux’s uveitis filing is the first for voclosporin in any indication, in any country. Clinical data has shown that Luveniq, also known as LX211, at the recommended dose of 0.4 milligrams per kilogram twice daily, provides clinically meaningful efficacy and enables preservation of vision in treated patients. Dr. Grau says there is significant unmet medical need in uveitis, a relatively rare eye condition in which corticosteroids are the only approved treatment.

“For the most severe forms we are targeting, which involve the back and the intermediate part of the eye, you cannot treat topically, and you need systemic treatment,� Dr. Grau notes.

As a result, he says, patients are often given systemic oral steroids at levels that can trigger major downstream morbidities.

“What the community is trying to do is to reduce steroids to a level under 10 milligrams a day and then bring in some other drug to help control inflammation,� Dr. Grau says.

Uveitis affects more than 300,000 people in the United States, almost 10% of which go blind every year. The majority of patients are first diagnosed under 40 years of age, making the socioeconomic burden of the disease greater than other serious eye conditions such as age-related macular degeneration and diabetic macular edema.

“Many [uveitis] patients are in the prime of their lives,� Dr. Grau says.

With potential access to two huge markets in the near future, Lux leaders are mulling commercial partnering options for Luveniq.

“Although clearly we could launch the product as a small company and build a franchise around it and perhaps develop a full-fledged ophthalmic company, the fact is the public markets have been very difficult lately,� Dr. Grau says. “Maybe they’re opening some now, but the public-market absence is obviously a determinant in terms of our financing needs.�

Tags: biotechnology, eye disease, Luveniq, regulatory