Rheumatology Drug Updates: Opioid CR845 for OA Pain; RA Treatments in Development

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CR845—an oral, peripherally selective kappa opioid agonist—is currently in Phase 2 trials for the treatment of pruritus, and acute and chronic pain.¹ Eighty patients with hip osteoarthritis (OA) or knee OA were randomized to receive treatment with 0.25 mg, 0.5 mg, 1.0 mg or 5.0 mg CR845 twice daily for two weeks. Safety assessment, pharmacokinetics and drug efficacy were evaluated. Joint pain efficacy was evaluated as a change from baseline in the Numeric Rating Scale (measured daily) and the change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), measured at the end of Weeks 1 and 2. Change from baseline in the use of rescue medications and Patient’s Global Assessment was also evaluated.

The mean joint pain score showed a dose-related reduction from baseline: 25% for patients treated with 0.25 mg CR845 and up to 34% for patients treated with 5.0 mg CR845. Half of the patients in this latter group had at least a 30% reduction in their mean pain score and a higher mean reduction in the joint pain score compared with the other treatment groups. In addition, these patients had an 80% decrease in the mean rescue medication use. Fifty-nine percent of these patients had not used rescue medication by Week 2. WOMAC scores were significantly improved in all four treatment groups. The patients treated with 5.0 mg CR845 had a 38% improvement in WOMAC scores compared with baseline.

Olokizumab to Treat RA

Olokizumab (OKZ)—a humanized, anti-interleukin-6 monoclonal antibody—is being developed to treat moderate to severe rheumatoid arthritis (RA).² The efficacy and safety of OKZ were assessed in 12-week randomized, controlled trials in patients who had previously failed treatment with anti-TNF therapies. In these trials, the primary study objective was to assess the long-term safety of OKZ. The secondary objective was to assess its long-term efficacy using a change from baseline in the Disease Activity Score 28 C-reactive protein (DAS28 [CRP], four variable).

Patients received placebo or 60 mg, 120 mg or 240 mg OKZ subcutaneously every two or four weeks in one study. In the second study, patients received 240 mg OKZ every two weeks or 8 mg/kg tocilizumab intravenously every two weeks. Patients who completed the trials were eligible for an open-label extension, in which all participants received 120 mg OKZ subcutaneously every two weeks plus methotrexate (12.5–25.0 mg a week to Week 12, after which the dose could be decreased).

The two studies were to be carried out for five years, but both were stopped prematurely at Week 90 and Week 89, respectively. Patients who received OKZ for six or more months in the open-label extension were considered to have completed the studies. Measures of efficacy improved in the open-label extension for patients who switched from placebo to OKZ. Disease activity in each treatment group decreased.

Treatment-emergent adverse events occurred in 88–95% of patients in both studies. Reactions included upper respiratory and other infections, arthralgia, diarrhea, stomatitis, cough and injection site pain. OKZ was tolerated, with an expected safety profile, and reductions in disease activity were sustained to Week 48.

Secukinumab Receives 2 New Approvals: PsA & AS

Secukinumab (Cosentyx) was approved by the FDA in January for the treatment of adults with active ankylosing spondylitis (AS) and active psoriatic arthritis (PsA).³

Secukinumab was initially FDA approved in 2015 to treat adult patients with moderate to severe plaque psoriasis. Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. It is administered as a subcutaneous injection.

These two new approvals are based on the safety and efficacy outcomes from four placebo-controlled Phase 3 trials in more than 1,500 adults with AS or PsA. Patients were either biologic treatment-naive or had an inadequate response or were intolerant to anti-tumor necrosis factor alpha (TNF-α) therapies. Primary study endpoints in these trials were achieving statistically significant improvements (vs. placebo) in the signs and symptoms of PsA and AS, measured by a 20% reduction in the American College of Rheumatology (ACR 20) response criteria at Week 24, and by at least a 20% improvement in the Assessment of Spondyloarthritis International Society criteria (ASAS 20) at Week 16, respectively.

More than 9,600 patients used secukinumab in the clinical trial programs for many uses, with more than 15,000 psoriasis patients treated post-marketing. No new safety signals have been identified. The most common adverse reactions in clinical trials were diarrhea, nasopharyngitis and upper respiratory tract infection.⁴

Cosentyx is available as a 150 mg/mL solution for injection in a single-use Sensoready pen, as 150 mg/mL solution for injection in a single-use prefilled syringe and as 150 mg in a lyophilized powder for injection in a single-use vial for reconstitution for healthcare professional use only.

Dosing Recommendations for Cosentyx

AS: With a loading dose, administer 150 mg SC at Weeks 0, 1, 2, 3 and 4, and every four weeks thereafter. Without a loading dose, administer 150 mg subcutaneously every four weeks.

PsA: With concomitant moderate to severe plaque psoriasis, administer 300 mg subcutaneously at Weeks 0, 1, 2, 3 and 4, and then 300 mg every four weeks thereafter (the plaque psoriasis dosing). For some patients, a lower dose of 150 mg may be acceptable.

PsA (other): Secukinumab may be administered with or without a loading dosage. With a loading dose, administer 150 mg subcutaneously at Weeks 0, 1, 2, 3 and 4, and every four weeks thereafter. Without a loading dose, administer 150 mg subcutaneously every four weeks. If PsA persists, consider using the higher dosage of 300 mg.

Secukinumab (Cosentyx) is to be used under the guidance and supervision of a physician. When deemed appropriate after proper training in subcutaneous injection technique, patients may self-administer using the Sensoready pen or prefilled syringe. The lyophilized powder is for healthcare provider use only. The drug should be administered at a different anatomic location (such as upper arms, thighs or any quadrant of the abdomen) than the previous injection and not into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis.

Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Barber J. Cara Therapeutics reports positive mid-stage data for CR845 in osteoarthritis. FirstWord Pharma. 2016 Dec 9.
2. Genovese MC, Fleischmann R, Tanaka Y, et al. Long-term safety and efficacy of olokizumab in patients with moderate-to-severe rheumatoid arthritis who have previously failed anti-TNF treatment. Arthritis Rheumatol. 2015 Oct; 67(suppl 10).
3. Novartis receives two new FDA approvals for Cosentyx to treat patients with ankylosing spondylitis and psoriatic arthritis in the US. Novartis press release. 2016 Jan 15.
4. Cosentyx (secukinumab) product labeling. Novartis. Updated January 2016.