You Might Also Like
Explore This IssueFebruary 2014
Also By This Author
Biosimilars are currently coursing through clinical trials in the U.S. with the hopes of garnering approval by the Food and Drug Administration (FDA) in coming years. At present, Europe is ahead of the U.S. regarding biosimilar guidelines and biosimilar products.1 To-date, 14 biosimilar products for human use have received marketing authorization by the European Medicines Agency (EMA). The European biosimilar guideline was released in 2006, and updates were posted online on October 6, 2013, for a six-month public consultation. Subsequent to this, the guideline will be formally available.
In the U.S., adalimumab is set to lose its patent in December 2016.2 A few manufacturers have already stepped up to develop biosimilars to this blockbuster agent that had annual U.S. sales (in 2012) of more than $9 billion.
- A phase I, double-blind, randomized, parallel-group, single-dose, three-arm study has enrolled healthy volunteers to receive PF-06410293 (Pfizer’s adalimumab biosimilar) compared to U.S. and European sourced adalimumab (Humira) in the REFLECTIONS B-538-01 trial.3 This study aims to show equivalent pharmacokinetic parameters to adalimumab over 43 days. Female and male patients aged 18 to 55 years received 40 mg/0.8 mL administered by subcutaneous injection with a single-use prefilled syringe during the course of this investigation.
- Boehringer Ingelheim’s adalimumab biosimilar, BI 695501, completed a phase I trial involving 193 healthy male subjects aged 18 to 55 years.4 This trial was completed in July 2012; no results have yet been reported, and the status of this investigation is not currently known.5
- Further along in the potential biosimilar approval process is Amgen, with its version of an adalimumab biosimilar, ABP 201.6 ABP-501 is being investigated in a multicenter, randomized, double-blind, active-controlled, parallel-group, 24-week efficacy study in 500 patients aged 18 years and older with moderate to severe rheumatoid arthritis (RA). Equivalent efficacy to branded adalimumab is being evaluated with the ACR20. The study is expected to take 11 months to complete.
- Finally, Sandoz, a division of Novartis that produces generic drugs, has begun a phase III clinical trial of its biosimilar version of adalimumab to demonstrate similarity, equivalent efficacy, and immunogenicity to branded adalimumab in patients with moderate to severe plaque psoriasis.7
Sandoz has also commenced phase III clinical trials for an etanercept biosimilar, GP2015, also to treat moderate-to-severe plaque psoriasis.8 Sandoz may have chosen moderate to severe plaque psoriasis rather than RA to evaluate due to the possibility of being able to better extrapolate psoriasis data to other etanercept indications once approved. The etanercept study is expected to be completed in November 2015, with subsequent U.S. and European regulatory filings.
Etanercept had U.S. sales of more than $4.2 billion, making it a lucrative biosimilar target, with many potential postapproval indications.9 The following companies all have etanercept biosimilars in clinical development: Biocon/Mylan, Celltrion, Daiichi Sankyo/Coherus Bioscience (CHS-0214), and Mycenax (TuNEX, Phase 3).8-10 The Daiichi Sankyo/Coherus Bioscience (CHS-0214) etanercept biosimilar has shown comparable pharmacokinetics to etanercept in a pivotal clinical study.8 In its current collaborations, Coherus plans on pursuing further etanercept biosimilar development in order to gain approvals in the U.S. and abroad.
Other potential biosimilars to rheumatologic products such as rituximab and infliximab are also being sought.2,11 At least one rituximab biosimilar (PF-05280586) is currently in phase II trials.
Pipeline and Drug Approvals
Afrezza, an inhaled form of insulin powder, has been submitted to the FDA for treating types 1 and 2 diabetes mellitus.12 The FDA received the New Drug Application for Afrezza, a drug–device combination, in October 2013. In early 2011, the FDA informed Afrezza’s maker, MannKind, that it needed more efficacy and safety proof using an improved version of the inhaler device (earlier studies used a previous version of the device). The Prescription Drug User Fee Application date is April 15, 2014, and the FDA’s advisory panel will be meeting in advance of that date.
CF101, an oral A3 adenosine receptor (A3AR) agonist, led to ACR20 response by three months in 49% of patients, versus 25% of placebo-treated patients.13 ACR50 and ACR70 improvements were noted in 19% of treated patients, compared to 9% of placebo-treated patients, and 11% of treated patients compared to 3% of placebo-treated patients, respectively. This was a phase IIb study in 79 RA patients who all had elevated A3 adenosine receptor biomarker levels at baseline.
In late December, the FDA approved the first generic of duloxetine (Cymbalta).14 The branded product is FDA approved to treat chronic musculoskeletal pain, fibromyalgia, generalized anxiety disorder, diabetic neuropathic pain, and major depressive disorder.
Dr. Kaufman is a freelance medical writer based in New York City, a pharmacist at New York Presbyterian–Lower Manhattan Hospital, a certified geriatric pharmacist, and adjunct faculty at Touro College of Pharmacy.
- Revised guideline on biosimilars containing biotechnology-derived proteins published for pubic consultation. Published October 6, 2013. www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001811.jsp&mid=WC0b01ac058004d5c1. Accessed December 27, 2013.
- Pfizer to start trial for biosimilar adalimumab. Published June 21, 2013. www.gabionline.net/Biosimilars/News/Pfizer-to-start-trial-for-biosimilar-adalimumab. Accessed January 2, 2014.
- Study of PF-06410293 and adalimumab in healthy subjects (REFLECTIONS B538-01). Published January 1, 2014. http://clinicaltrials.gov/ct2/show/NCT01870986?term=to+PF-06410293&rank=1. Accessed January 2, 2014.
- Pharmacokinetics and safety study of BI 695501 in healthy subjects. Published December 12, 2012. http://clinicaltrials.gov/ct2/show/NCT01505491?term=BI+695501&rank=1. Accessed January 2, 2014.
- Boehringer Ingelheim pipeline. Published January 2, 2014. www.boehringer-ingelheim.com/research_development/drug_discovery/pipeline.html. Accessed January 2, 2014.
- Amgen to start phase III trial for biosimilar adalimumab. Published September 27, 2013. http://gabionline.net/Biosimilars/News/Amgen-to-start-phase-III-trial-for-biosimilar-adalimumab. Accessed January 2, 2014.
- Sandoz begins Phase II clinical trials for biosimilar adalimumab. Published December 19, 2013. www.biosimilarnews.com/sandoz-begins-phase-iii-clinical-trial-for-biosimilar-adalimumab. Accessed January 2, 2014.
- Sandoz to start Phase III etanercept trial Published May 24, 2013. http://gabionline.net/Biosimilars/News/Sandoz-to-start-phase-III-etanercept-trial. Accessed January 2, 2014.
- Etanercept biosimilar has comparable pharmacokinetics to Enbrel. Published November 15, 2013. http://gabionline.net/Biosimilars/Research/Etanercept-biosimilar-has-comparable-pharmacokinetics-to-Enbrel/%28highlight%29/coherus%20enbrel. Accessed January 2, 2014.
- Company to pursue next stage of development as part of collaboration with Daiicho Sankyo and Baxter. Published October 29, 2013. www.coherus.com/newsroom/recent-news. Accessed January 2, 2014.
- Walsh N. Biosimilar of Remicade holds up at 2 years. Published October 29, 2013. www.medpagetoday.com/MeetingCoverage/ACR/42551. Accessed January 2 2014.
- White RD. MannKind is seeking approval of diabetes inhaler system by spring. Published December 8, 2013. www.latimes.com/business/la-fi-stock-spotlight-mannkind-20131209,0,7194142.story#axzz2nNJI30ZM. Accessed December 13, 2013.
- Walsh N. Oral RA drug shows promise in early trial. Published December 26, 2013. www.medpagetoday.com/Rheumatology/Arthritis/43582. Accessed December 27, 2013.
- Cassels C. FDA okays first Cymbalta generics. Published December 11, 2013. www.medscape.com/viewarticle/817689. Accessed January 2, 201