Flexion Phase II data for FX005 gives clinical PoC in arthritis pain
This article was originally published in Scrip
Flexion Therapeutics reported topline data from a Phase II proof-of-concept study that showed that its lead anti-inflammatory drug candidate FX005 was well-tolerated, provided sustained pain relief and improved joint function for patients with moderate osteoarthritis in the knee.
FX005, a sustained-release analgesic administered with an intra-articular injection, is positioned as a second-line therapy following steroids injected at the site of knee joint pain. Flexion CEO Michael Clayman said the Phase II data validated the company's approach to osteoarthritis, which is focused on local-acting agents that minimize systemic side effects.
Flexion claims that the clinical trial was the first-ever study to demonstrate the efficacy of a p38 MAP kinase-inhibitor in osteoarthritis patients, but the Woburn, Massachusetts-based company does not plan to release detailed data until a future medical conference.
In the randomized, double-blind, placebo-controlled Phase II study, the 104 patients who received FX005 or a placebo via intra-articular injection were evaluated at two, four, eight and 12 weeks using the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. FX005 demonstrated significant pain relief compared to placebo at four weeks as well as prolonged relief and increased joint function throughout the study's 12 weeks.
"Intra-articular steroids work very well in osteoarthritis, but they only work for a few weeks and you can only get injections every three months," said Dr Clayman.
He said the Phase II data for FX005 is "very-gratifying," since many anti-inflammatory drugs do not provide functional improvements for osteoarthritis patients.
There are 27 million US adults and 100 million people worldwide with osteoarthritis and the numbers are rising quickly due to the aging and increasingly obese population as well as a rise in sports injuries that eventually lead to arthritis.
Dr Clayman said there is a significant unmet medical need for a local-acting agent that minimizes systemic effects on the body. Because in addition to the short duration of pain relief from steroids injected at the site of joint pain, he said oral osteoarthritis drugs also have limited efficacy and their labels list several cardiovascular, liver and gastrointestinal side effects as well as black box warnings about serious adverse events.
FX005 is just one of three local-acting novel drug candidates in Flexion's pipeline for mild, moderate and severe osteoarthritis pain. The initial focus is pain relief, but both FX005 and FX006 have the potential to be "disease-modifying," because of their impact on joint function.
FX006 is a novel, proprietary, sustained-release formulation of triamcinolone acetonide for mild to moderate osteoarthritis of the knee. The drug, which is entering into a Phase IIb dose-ranging study, is being developed under the US FDA's 505(b)2 approval pathway for medications that rely on previously reviewed clinical trial data.
The preclinical FX007 is a novel, proprietary antagonist of TrkA, a neuronal receptor in the articular tissues. The drug will be developed to treat advanced osteoarthritis with pain that is refractory to available treatments.
Both orthopaedists and rheumatologists are on the hunt for more and better treatments for osteoarthritis pain.
In relation to FX005, Timothy McAlindon, chair of rheumatology and professor of medicine at Tufts Medical Center, said in a statement from Flexion that: "Physicians and patients need targeted treatments for osteoarthritis that are more effective and longer lasting. These [Phase II] results represent a significant advance in that direction, so we will eagerly monitor development of this new treatment."
After injections with corticosteroids, such as Kenalog, and hyaluronic acids, such as Genzyme's Sinvisc (hylan G-F 20), doctors have few options aside from knee replacement therapy.
"New and more effective pain relief could logically lead to a delay in the need for surgery," Dr Clayman said. "We are not pursuing FX005 as an alternative to knee replacement, but doctors are interested in it, because it could delay the need for it."
The next step for FX005 is a Phase IIb dose-ranging study in preparation for Phase III testing. Dr Clayman said Flexion has a group of investors who have provided enough funding to take the private company into early 2013, but it likely will raise new cash before then.
"We're confident this data will facilitate those financing activities," he said.
Flexion raised $33 million in a Series A round led by Versant Ventures in 2009 (scripintelligence.com, 20 October 2009) and added $9 million from Pfizer to the Series A funding in 2010 (scripintelligence.com, 1 February 2010).