Friday, February 15, 2013

ARRY-797 at the ACR2012 in Washington

There has been a late breaking abstract on ARRY-797 about ... osteoarthritis. ARRY-371797 is a p38 inhibitor. There have been some studies on the way:
• A Study of ARRY-371797 in Patients With Rheumatoid Arthritis
• A Study of ARRY-371797 in Patients With Active Ankylosing Spondylitis
These studies had been completed by July 2012, but nothing has been published at the EULAR 2012 meeting in Berlin or at the ACR 2012 meeting in Washington. And then a late breaking poster on osteoarthritis. What does it mean? My guess is that p38 inhibition isn’t working in RA and AS, but the producer (Array BioPharma) is looking desperately for an indication to put the drug on the market. OK, let’s have a closer look, if ARRS-797 is a candidate to treat osteoarthritis.

Alan J. Kivitz and colleagues presented the following study [Abstract No. L1]: “A Randomized, Placebo-Controlled Phase 2 Study of ARRY-797 in Patients with Osteoarthritis Pain Refractory to NSAID Treatment Showed Statistically Significant Improvements in WOMAC Pain and in Biomarkers of Bone and Cartilage Degradation.” Conclusion: “ARRY-797 treatment resulted in durable, statistically significant improvement in OA pain and in reduction of circulating biomarkers of both cartilage and bone degradation in this 4-week study. Further evaluation of the efficacy of this non-opioid analgesic and the potential for disease modifying activity are warranted.”

Wait a Minute! Let’s have a closer look at the results of the WOMAC Pain Score!

Change from Baseline in WOMAC Pain (0-10 NRS)
Study Visit    ARRY-797    Placebo    Oxy ER
Week 1            1.6*             0.9           2.0*
Week 2            1.7              1.3           2.0*
Week 3            2.1              1.7           2.0
Week 4            2.4*             1.6           1.9
BOCF/LOCF. * p _0.05 (2-sided) versus Placebo

“Durable improvement” – ARRY-797 is significantly better than placebo only at week 1 and week 4. The pain reduction of ARRY-797 at week one is equal to placebo at week 4. At best ARRY-797 reduces the pain better than placebo by 0.8 on the NRS. Let’s put the initial pain score at 8.5, placebo would reduce this to 6.9 and ARRY-797 to 6.1. Big deal! Even the much criticized study of L.A. Crofford on pregabalin in fibromyalgia worked with a pain reduction of at least 50% against baseline. ARRY-797 is very far from this goal.

The authors also listed some adverse events in patients treated with ARRY-797: “mild to moderate skin-related disorders, dizziness, diarrhea and stomatitis. Transient increases in CK and mild prolongations in the QTc interval were also noted.”

Well, I don’t think ARRY-797 is a good candidate for a drug on treating osteoarthritis. ARRY-797 hasn’t yet shown so much efficacy to warrant already noticed risks and expected costs.

Nothing new on ARRY-797 at the EULAR Meeting 2013 in Madrid. But according to the homepage of Array Biophama the project isn't abandoned. Not working in RA and AS, and only mild effects in OA. It seems strange that the company ran for a late breaking poster and doesn't publish more now. I don't see ARRY-797 on the market.

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