Etoricoxib and Riquent filed for approval in US

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Jan 13, 2002

Etoricoxib and Riquent filed for approval in US

Rockville, MD - Several companies have reported on progress with drugs

destined for the rheumatology marketplace over the past few weeks. In the

US, Merck & Co has refiled its new drug application (NDA) for etoricoxib

(Arcoxia®) and La Jolla Pharmaceuticals has filed an NDA for RiquentTM

(abetimus) in lupus. Separately, Isis Pharmaceuticals has reported positive

data from a phase 2 clinical trial in rheumatoid arthritis with its

antisense TNF inhibitor ISIS-104838 and Human Genome Sciences has begun a

phase 2 study in RA with Lymphostat-B, a human monoclonal antibody to the

B-lymphocyte stimulator BLyS.

Etoricoxib, Merck & Co's second-generation selective COX-2 inhibitor,

following on from rofecoxib (Vioxx®), is already available in many European

countries and elsewhere. In the US, however, the company withdrew the

original NDA for etoricoxib in March 2003, and the FDA requested further

information about acute pain indications and cardiovascular safety. The new

NDA covers use of the product in osteoarthritis, rheumatoid arthritis,

chronic low back pain, acute pain, dysmenorrhea, acute gouty arthritis, and

ankylosing spondylitis. This label is broader than that for any existing

coxib, as none of the others is approved for chronic low back pain, acute

gouty arthritis, or ankylosing spondylitis.

However, in Europe, an originally broader labeling, approved for etoricoxib

in the UK in April 2002, was curtailed during the European mutual

recognition procedure, when the indications of chronic low back pain, acute

pain in dental surgery, and dysmenorrhea were removed, as previously

reported on rheumawire.

Riquent (abetimus, previously known as LPJ 394) is La Jolla Pharmaceutical's

lead product candidate and is destined for use in the treatment of systemic

lupus erythematosus (SLE) patients at risk of renal disease. The drug

targets antibodies to double-stranded DNA (dsDNA). The company says its NDA

submission is based primarily on data from a phase 3 trial involving 298

lupus patients and also a previous phase 2/3 trial involving 189 patients.

The company says: " We believe these studies show that patients treated with

Riquent experienced reductions in the levels of antibodies to dsDNA and that

reductions in these antibodies were associated with fewer renal flares.

These results were seen even though many patients were on immunosuppressive

drug therapies. "

However, as previously reported by rheumawire, the pivotal phase 3 trial

failed to meet its primary end point of reducing the time to renal flare,

and while the company emphasizes the link between antibodies to dsDNA and

lupus and kidney disease, there is still some debate about this association

within the scientific community. One expert told rheumawire that dsDNA

antibodies are not yet accepted as a surrogate marker for the disease and

commented that the effects seen in the clinical trials with Riquent are

interesting but modest.

Progress in RA clinical trials

Separately, progress in clinical trials in rheumatoid arthritis has been

reported with 2 novel approaches to therapy.

Human Genome Sciences announced that in addition to starting a phase 2

clinical trial in 230 patients with rheumatoid arthritis with LymphoStat-B,

it already has a phase 2 study ongoing in patients with SLE. These studies

represent the most advanced clinical testing in this new research field,

opened up by the discovery of the B-cell stimulator BlyS (also known as

BAFF) in 1999. It's an approach that has generated quite a bit of

excitement, as previously reported on rheumawire, as it involves targeting

the autoimmunity at the root of both diseases. " Emerging clinical and

preclinical evidence suggest that B-cell antagonists, such as LymphoStat-B,

have the potential to reduce autoantibody levels and help reduce disease

progression, " says Human Genome Sciences.

Isis Pharmaceuticals is a genomics-based drug development company

specializing in antisense products, which intervene at the level of RNA to

prevent the production of proteins involved in disease. The company has

already commercialized 1 such product (for the ophthalmology market) and is

working on several others, including an antisense TNF- inhibitor, ISIS

104838, for use in rheumatoid arthritis. Last week, the company announced

positive data from a phase 2 trial in 176 RA patients, saying that patients

in the 2 highest dose groups showed improved ACR20 scores compared with

those on placebo (although the difference was not statistically significant)

and also had fewer swollen and tender joints. A previous study has shown

that the product accumulates in a dose-dependent manner in the synovial

tissue and that it reduced TNF- mRNA levels. Although the product currently

in trials is an injectable, the company is working to develop an orally

active formulation.

Zosia Chustecka