Rheumatology Drug Updates, Trials, Safety Data

Biosimilar Update

In early April, Delaware became the first state to pass a biosimilar law, allowing a retail pharmacist to substitute or interchange a biosimilar product for an originator biological product if the prescriber did not prohibit a substitution.¹ The law requires the pharmacist to record information on the label and dispensing record of the substitution, inform the patient of the substitution and also notify the prescriber of the substitution within 10 days of doing so. All related pharmacy records must be kept for at least three years.

Key points of the legislation include transparency and open lines of communication between patients, prescribers and other members of the healthcare team (e.g., pharmacists). The Biotechnology Industry Organization and the Delaware BioScience Association support the legislation; however, the Biologics Price Competition and Innovation (BPCI) Act of 2009 conflicts with the new legislation because it states that an interchangeable biological product may be substituted for the reference product without healthcare provider intervention. The Generic Pharmaceutical Association believes that because the Food and Drug Administration (FDA) has yet to pass final biosimilar guidance, individual state legislation (such as this) is not currently necessary.

Colorado, Florida, Indiana and North Dakota have all passed similar legislation.^2,3 The BPCI Act became law in 2010 and established an abbreviated approval pathway for biological products that are confirmed to be “highly similar” to (biosimilar) or “interchangeable” with an FDA-approved biological product.⁴

Six states have failed to pass biosimilar legislation (i.e., Arizona, Arkansas, Maryland, Mississippi, Texas, Washington), and five states (i.e., California, Colorado, Illinois, Massachusetts and Pennsylvania) are considering legislation.

In the U.S., only around 5% of the total volume of top biological products are distributed by retail pharmacies. As previously noted (see the February 2014 article on biosimilars in this publication), other countries are much further ahead of the U.S. in relation to biosimilar approvals. Most recently, on April 17, the Russian Ministry of Health approved Biocad’s biosimilar rituximab (AcellBia; BCD-20) to Roche Laboratories MabThera/Rituxan.⁵

Pipeline & Drug Approvals

Celecoxib (Celebrex) may see its U.S. debut later this year due to a patent settlement between Teva Pharmaceuticals generic division and Pfizer Inc.⁶ The branded product continues to have blockbuster status, having U.S. sales greater than $2 billion in 2013.

Gevokizumab, a once-monthly, antiinflammatory, monoclonal antibody injection in Phase 2 clinical trials for the treatment of erosive osteoarthritis of the hand, will no longer be studied for this indication due to weak efficacy results.^7,8 Gevokizumab currently has orphan drug status for treating pyoderma gangrenosa, Behçet’s uveitis and noninfectious uveitis. Other indications are being sought.

The five-year clinical efficacy, radiographic and safety findings of subcutaneous golimumab (Simponi) in treating adults with active psoriatic arthritis were recently reported.⁹ ACR20 responses after Week 252 occurred in 63–70% of patients that received once weekly 50 mg or 100 mg subcutaneous golimumab with or without methotrexate. Additionally, there was a greater than or equal to 75% improvement in the Psoriasis Area and Severity Index scores for 61–72% of patients with at least 3% of body surface area involvement. ACR50 responses were obtained in 43–51% of patients, and ACR70 responses were seen in 31–36% of patients. Among 267 patients who received methotrexate and had both baseline and five-year radiographs obtained, progression (radiographic) appeared to be slightly reduced. No new safety signals were identified.

Although the controversy around hydrocodone bitartrate extended-release (Zohydro ER) continues, a new hydrocodone bitartrate product with abuse-deterrent features moves closer to obtaining regulatory approval.¹⁰ Purdue Pharma’s hydrocodone bitartrate tablet is hard to crush and snort or inject, but Zohydro ER has no abuse-deterrent features. The not-yet-FDA-approved product is being investigated to treat low back pain, and it would likely be used for other types of pain if needed (off-label) once gaining approval. Hydrocodone-based products are some of the most widely prescribed drugs in the U.S. The FDA continues to tighten prescribing restrictions on opioid analgesics to help curb abuse, diversion and addiction.

If you were thinking, “Do we need another NSAID or a new formulation for one?” think again. The newest product is a lower dose indomethacin capsule, Tivorbex, in 20 mg and 40 mg strengths.¹¹ It is approved for treating mild to moderate acute pain in adults and carries the same warnings as other NSAIDs, as well as the same adverse effects of other indomethacin products.

The generic of Aciphex 20 mg tablets, rabeprazole sodium delayed-release tablets, is now available.¹²

The generic of Evista 60 mg tablets, raloxifene tablets, is now available.¹³ Teva Pharmaceuticals has market exclusivity until September 2014. At that time, additional generics should become available, and the price should decrease.

Drug Safety

Epidural corticosteroid injections, including betamethasone, dexamethasone, hydrocortisone, methylprednisolone, triamcinolone and others, carry the risk of rare, but serious neurologic problems.¹⁴

This new FDA warning, although not related, brings back unfortunate memories of the 2012–2013 New England Compounding Center debacle related to cases of meningitis and patient deaths due to contaminated corticosteroid injections. The FDA warns that epidural corticosteroid injections may result in rare but serious adverse events, including paralysis, vision loss, stroke and death. The FDA states that the effectiveness and safety of epidural corticosteroid administration has not been established and is not FDA approved for this indication. New information is now required in the Warnings section of drug labels for injectable corticosteroids describing these risks.

Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York, a pharmacist at New York Presbyterian—Lower Manhattan Hospital, and adjunct faculty at Touro College of Pharmacy.

References

1. Delaware passes biosimilars substitution law. Generics and Biosimilars Initiative (GaBI). April 25, 2014. http://gabionline.net/Policies-Legislation/Delaware-passes-biosimilars-substitution-law?utm_source=GONL4&utm_campaign=1bd991b2c7-GONL+V14D25-4&utm_medium=email&utm_term=0_c68e980169-1bd991b2c7-111320173 certain restrictions. Last accessed April 25, 2014.
2. Indiana biosimilars substitution becomes law. Generics and Biosimilars Initiative (GaBI). March 28, 2014. http://gabionline.net/Policies-Legislation/Indiana-biosimilars-substitution-bill-becomes-law. Last accessed April 25, 2014.
3. Biosimilars bills move on in two states. Generics and Biosimilars Initiative (GaBI). March 15, 2013. http://www.gabionline.net/Policies-Legislation/Biosimilars-bills-move-on-in-two-US-states. Last accessed April 25, 2014.
4. US state legislation on biosimilars substitution. Generics and Biosimilars Initiative Journal (GaBI Journal). 2013;2(3):155–156. Available at http://gabi-journal.net/us-state-legislation-on-biosimilars-substitution.html.
5. Biosimilar rituximab approved in Russia. Generics and Biosimilars Initiative (GaBI). April 25, 2014. http://gabionline.net/Biosimilars/News/Biosimilar-rituximab-approved-in-Russia?utm_source=GONL4&utm_campaign=1bd991b2c7-GONL+V14D25-4&utm_medium=email&utm_term=0_c68e980169-1bd991b2c7-111320173. Last accessed April 25, 2014.
6. George J. Teva and Pfizer settle Celebrex patent dispute. Philadelphia Business Journal. April 17, 2014. http://www.bizjournals.com/philadelphia/blog/health-care/2014/04/teva-and-pfizer-settle-celebrex-patent-dispute.html?surround=etf&ana=e_article. Last accessed April 25, 2014.
7. Xoma to halt development of Gevokizumab in osteoarthritis indication. Genetic Engineering & Biotechnology News. March 5, 2014. http://www.genengnews.com/gen-news-highlights/xoma-to-halt-development-of-gevokizumab-in-osteoarthritis-indication/81249581. Last accessed April 25, 2014.
8. Manocha V. Xoma to stop testing drug as arthritis treatment; shares plunge. Reuters. March 5, 2014. http://mobile.reuters.com/article/idUSBREA241IP20140305?irpc=932. Last accessed April 25, 2014.
9. Kavanaugh A, McInnes IB, Mease P, et al. Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: Results from a long-term extension of a randomised, placebo-controlled trial, the GO-REVEAL study. Ann Rheum Dis. 2014 April 19. doi: 10.1136/annrheumdis-2013-204902. http://ard.bmj.com/content/early/2014/04/26/annrheumdis-2013-204902.full.
10. Armstrong D. Purdue pill may force Zogenix’s rival drug off market. Bloomberg. March 12, 2014. http://mobile.bloomberg.com/news/2014-03-12/purdue-pill-may-force-zogenix-s-rival-drug-off-market.html. Last accessed April 25, 2014.
11. Iroko Pharmaceuticals receives FDA approval for Tivorbex. Iroko Pharmaceuticals. Feb. 24, 2014. https://www.iroko.com/press-releases/iroko-pharmaceuticals-receives-fda-approval-for-tivorbex. Last accessed April 25, 2014.
12. Chavis R. Kremers Urban launches rabeprazole sodium tablets. Drug Store News. Feb. 20, 2014. http://www.drugstorenews.com/article/kremers-urban-launches-rabeprazole-sodium-tablets. Last accessed April 25, 2014.
13. Chavis R. Teva approved for generic Evista. Drug Store News. March 4, 2014 http://www.drugstorenews.com/article/teva-approved-generic-evista. Last accessed April 25, 2014.
14. Epidural corticosteroid injection: Drug safety communication—Risk of rare but serious neurologic problems. U.S. Food and Drug Administration. April 23, 2014. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm394530.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Last accessed April 25, 2014.