FDA Approves New Drugs for Pain

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FDA Updates

Belbuca, buccal-administered buprenorphine, has received U.S. Food and Drug Administration (FDA) approval for treating severe chronic pain.¹ The dosage form is a dissolving film that is absorbed through the inner lining of the cheek for chronic pain management. It’s expected to be commercially available in the first quarter of 2016. Seven dosage strengths will be available for flexibility. Doses will range from 75 μg to 900 μg to be administered every 12 hours.

The FDA has approved meloxicam capsules (Vivlodex) for managing osteo­arthritis (OA) pain.² It will be available in 5 mg and 10 mg doses for once-daily usage. This formulation uses low-dose pro­prietary SoluMatrix Fine Particle Technology with submicron meloxicam particles that are approximately 10 times smaller than their original size, resulting in faster dissolution. The Phase 3 clinical trial, from which the data that support the approval of this formulation were derived, was a 12-week multicenter, double-blind, placebo-controlled study of patients aged 40 and older (n=402) with OA pain of the knee or hip.

Lesurinad, a selective uric acid reabsorption inhibitor (SUI), was recommended for approval by an independent panel of FDA advisors for treating gout in a vote of 10 to 4.³ For primary issue, two doses were tested: 200 mg and 400 mg. The 400 mg dose was more effective at treating gout, but was also associated with more renal and cardio­vascular adverse events.

The manufacturer submitted only the 200 mg dose for approval, which was granted on Dec. 22, 2015, under the brand name Zurampic.⁴ The approved indication is for use in combination with a xanthine oxidase inhibitor, for treating hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.

There are still safety concerns with the 200 mg dose. The FDA safety profile vote resulted in a slim margin of approval: Seven to six, with one abstention. Zurampic carries a boxed warning related to acute renal failure with recommendations to monitor renal function throughout treatment. In addition, the agent should not be used as monotherapy.

The FDA has granted tentative approval for extended-release, abuse-deterrent oxycodone capsules (Xtampza ER) to manage pain severe enough to require around-the-clock, long-term opioid treatment for patients who find alternative treatments inadequate.⁵ The FDA determined that this product meets all the required safety, quality and efficacy standards for approval, but the approval is tentative due to ongoing litigation with Purdue Pharma (filed in March 2015). The product has received an automatic 30-month stay or availability hold. The FDA can provide final approval for the drug only if the litigation is resolved prior to the expiration of the 30-month period.

DETERx technology manufactured the product, which addresses common methods of abuse, including chewing, crushing and/or dissolving, and then snorting, injecting or taking it orally.

Obinutuzumab for Lupus Nephritis

Obinutuzumab, a CD20-directed cytolytic antibody that is FDA approved for treating chronic lymphocytic leukemia along with chlorambucil, is being investigated to treat lupus nephritis.⁶

The study, a Phase 2 clinical trial known as NOBILITY, will compare the safety and efficacy of 1,000 mg obinutuzumab in combination with corticosteroids and mycophenolate vs. corticosteroids and mycophenolate with placebo in patients with International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2003 Classification of Lupus Nephritis Class III or IV proliferative lupus nephritis. The primary outcome measure of NOBILITY is the percentage of patients who achieve complete renal response at Week 52.

Sub-Q Belimumab for SLE

BLISS-SC is a Phase 3 multicenter, randomized, double-blind, placebo-controlled, 52-week study to evaluate the efficacy and safety of belimumab administered sub­cutaneously to patients with active auto­antibody-positive systemic lupus erythematosus (SLE) receiving standard therapy.⁷ In this study, 200 mg belimumab (Benlysta) administered weekly and subcutaneously plus standard of care were shown to have significantly greater reductions in disease activity compared with placebo plus standard of care (61% vs. 48%).

The primary efficacy end point was the Systemic Lupus Erythematosus Responder Index response rate at Week 52.⁸ The belimumab regimen also met the secondary end point of delaying the time to severe flare (170 days) vs. placebo and standard care (117 days). Additionally, 18% of patients were able to reduce their steroid dose by 25% or more (for those taking >7.5 mg prednisone daily) compared with 12% of patients receiving the placebo and standard care regimen, which was not statistically significant.

Etanercept Biosimilars

In a 52-week clinical study, an investigational biosimilar for etanercept, SB4, showed lasting efficacy (including radiographic progression), immunogenicity and safety.⁹ This trial was a randomized, double-blind study in adults with moderate to severe rheumatoid arthritis (RA), despite methotrexate treatment.

Five hundred ninety-six patients were randomized to receive either SB4 (n=299) or Enbrel (etanercept; ETN) (n=297). The ACR20 response rate was 81% in patients who received SB4 vs. 82% in those who received ETN. Additionally, the ACR50 and ACR70 response rates were slightly higher for SB4 compared with ETN.

The safety profiles were also comparable. One treatment-emergent adverse event occurred in 59% of SB4-treated patients vs. 60% of ETN-treated patients; and injection-site reactions occurred in 4% vs. 18% of SB4- and ETN-treated patients, respectively (P<0.001). At Week 52, at least one anti-drug antibody result occurred in 1% and 13% of SB4- and ETN-treated patients, respectively (P<0.001). The serious infection, tuberculosis and malignancy rates were all comparable.

CHS-0214 is another investigational ETN biosimilar. The treatment met its primary endpoints in a confirmatory, double-blind, randomized, controlled, two-part Phase 3 study evaluating its efficacy and safety in patients with moderate to severe chronic plaque psoriasis.¹⁰ The efficacy endpoints were based on a 12-week assessment of Psoriasis Activity Severity Index (PASI) scores. The primary endpoints were the mean percent change in PASI from baseline and the proportion of patients achieving 75% improvement in PASI from baseline. These results met the pre-specified limits for demonstrating an equivalence to ETN. No clinically meaningful differences were noted in the safety profiles of the two products evaluated.

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. News release: U.S. FDA approves Belbuca (buprenorphine) buccal film for chronic pain management. 2015 Oct 26.
2. Iroko Pharmaceuticals LLC. New release: Iroko Pharmaceuticals receives FDA approval for Vivlodex—first low-dose SoluMatrix meloxicam for osteoarthritis pain. 2015 Oct 23.
3. Gray N. FDA cautiously recommends approval of AZ’s gout drug. BioPharma Dive. 2015 Oct 25.
4. U.S. Food & Drug Administration. Highlights of prescribing information [ZURAMPIC]. 2015 Dec.
5. Collegium Pharmaceutical Inc. News release: Collegium announces FDA tentative approval for Xtampza ER, a novel abuse-deterrent analgesic for chronic pain. 2015 Nov 9.
6. Genentech. News release: Genentech has announced the initiation of a phase 2 clinical trial investigating the use of obinutuzumab. 2015 Nov 2.
7. GlaxoSmithKline. News release: GSK announces positive results from phase 3 BLISS-SC study of Benlysta (belimumab) administered subcutaneously in patients with systemic lupus erythematosus. 2015 Nov 7.
8. McKee S. GSK’s lupus drug Benlysta hits PhIII targets. PharmaTimes. 2015 Nov 9.
9. Encovsky J, Sylwestrzak A, Leszczyñski P, et al. A phase 3, randomized, double-blind clinical study comparing SB4, an etanercept biosimilar, with etanercept reference product (Enbrel) in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy (52-week results). Arthritis Rheumatol. 2015 Sep; 67(9, suppl 10).
10. Coherus BioSciences Inc. New release: Coherus and Baxalta announce CHS-0214 (investigational etanercept biosimilar) met primary efficacy endpoints in phase 3 psoriasis clinical study (RaPsODY). 2015 Nov 10.