Humira during 2014 remained the world’s best-selling prescription medicine; Sovaldi vaulted into second place in its first full year on the market; Harvoni is challenging Humira for the 2015 sales crown.
The precipitous patent cliff of 2012 assaulted Big Pharma to the tune of up to $53 billion worth of prescription drug sales potentially lost to patent expirations. 2015 represents the next highest total since then, with a projected figure of $44 billion in sales that could be lost due to expired patents. This time, however, the brunt is expected to be much less widespread than the 2012 impact as more than sixty percent of the sales are tied to biotechnology drugs that are not yet facing biosimilar competition in the United States and in some other major markets despite losing exclusivity in 2015. As a result, generics have been forecasted to erode $16 billion in prescription-drug sales this year.
With most blockbuster biotech brands expected to continue to thrive in the near term minus significant biosimilar competition, the pharma/biotech industry is experiencing a substantial growth period. Global prescription drug sales have been projected by various industry analysts to continue growing, at nearly a five percent rate annually until 2020. Aiding the growth rate is a new wave of first-in-class blockbuster products and a recent increase in research and development productivity. A total of 41 new molecular entity and new therapeutic biological products were approved by the U.S. Food and Drug Administration during 2014, the second-highest total ever (there were 53 new drug approvals by FDA in 1996). Also contributing to the yearly Rx drug growth is a massive sales eruption from new hepatitis C treatments that began in fourth-quarter 2013 and continues to surge during 2015.
Humira leads the pack
For the third consecutive year, Humira was the top-selling prescription medicine. During 2014, the biologic therapy generated global sales of about $12.86 billion between marketers AbbVie Inc. and Eisai Co. Administered as a subcutaneous injection, Humira (adalimumab) is approved for a variety of autoimmune diseases. The medicine stems from the anti-tumor necrosis factor alpha monoclonal antibody drug class.
Launched in the United States during January 2003, Humira is available in more than 87 countries including Japan, China, Brazil, and Australia. The product is used for treating over 850,000 patients across 13 globally approved indications.
In North America and the European Union, the drug is marketed for rheumatoid arthritis (moderate to severe), psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, plaque psoriasis (moderate to severe), and juvenile idiopathic arthritis. In the United States, Humira is available for ulcerative colitis (moderate to severe), axial spondyloarthropathy, and pediatric Crohn’s disease (severe). Humira is also approved in the EU for pediatric enthesitis-related arthritis. According to AbbVie’s second-quarter 2015 report, the company recently received clearance from the EMA for a new Humira formulation specifically designed to reduce injection pain and reduce injection volume.
Also during first-half 2015, AbbVie announced results from VISUAL‑I, a Phase III trial investigating the efficacy and safety of Humira in adult patients with uveitis. Results demonstrated that the drug significantly lowered patients’ risk of uncontrolled uveitis or vision loss. AbbVie has gained orphan drug designation from U.S. regulators for the investigational treatment of certain forms of non‑infectious uveitis with Humira. U.S. and EU regulatory filings are expected during second-half 2015, following positive results from the second pivotal study.
For first-half 2015, AbbVie reported Humira global sales of $6.65 billion. January-June 2015 international sales rose almost 9 percent on an operational basis. Strong U.S. growth for Humira continued throughout second-quarter 2015, spurred by double-digit growth across all three major market categories: rheumatology, dermatology and gastroenterology.
The U.S. composition of matter patent covering adalimumab is scheduled to expire during December 2016. The equivalent EU patent is slated to run its course in the majority of those countries by April 2018.
Despite those compound patent expirations in 2016 and 2018, Humira sales are expected to continue thriving on a global scale due to the lack of biosimilar competition in most major markets. Analysts from EvaluatePharma have projected that Humira worldwide sales will approach $14 billion in 2020.
Hepatitis C drugs produce unprecedented launches
Coming in at the No. 2 spot among the world’s top-selling Rx medicines for 2014 is Sovaldi, which temporarily accounts for the best 12-month opening performance ever for a prescription product. To put this drug’s remarkable market ascension in perspective, the Gilead Sciences Inc. chronic HCV infection medicine was not even approved for use anywhere worldwide when Med Ad News last published this special report during July 2013. FDA marketing clearance came in December 2013 and EU regulatory approval arrived the following month. By the end of 2014, Sovaldi had produced worldwide sales of $10.28 billion. Only a handful of prescription drugs have ever topped $10 billion in annual sales, and none of them accomplished the feat in such quick fashion.
Containing the main ingredient sofosbuvir, Sovaldi is marketed in 40-plus countries for treating chronic hepatitis C (CHC) virus infection. By year-end 2014, over 170,000 chronic HCV patients had been treated with a Sovaldi-containing regimen since the drug’s first approval about one year earlier. The medicine is classified as a once-daily nucleotide analog polymerase inhibitor.
Marketing clearance in Japan arrived during March 2013 for Sovaldi, making it part of the first all-oral treatment regimen for genotype 2 patients in that country. Mainly because of HCV, Japan has one of the highest rates of liver cancer of any industrialized nation. Other marketed therapies in Japan for genotype 2 HCV infection involve 24-48 weeks of injections with pegylated interferon, which may not be suitable for many patients.
Sovaldi is truly emerging as a global brand. During September 2014, deals were established with seven Indian pharmaceutical manufacturers that enable the manufacturing of Sovaldi for distribution in 91 developing countries in which an estimated 100 million people are infected with hepatitis C. The drug has been approved for marketing in India, Mongolia, and Pakistan and marketing authorization applications have been submitted in at least 10 other emerging and developing countries.
According to Gilead, Sovaldi has patent protection until 2028 in the European Union and 2029 in the United States. During the first six months of 2015, Sovaldi sales – while still thriving at blockbuster status – were down significantly compared to the one-year-earlier period because of competition from a fellow Gilead HCV drug known as Harvoni. For January-June 2015, Sovaldi global sales reached $2.26 billion versus the first-half 2014 total of $5.76 billion.
Based on first-half results, Harvoni could eclipse Humira as the world’s top-selling prescription drug for calendar-year 2015. Harvoni sales for January-June 2015 amounted to $7.19 billion. Containing the active ingredients ledipasvir (90 mg) and sofosbuvir (400 mg), Harvoni received green-light marketing status in the United States on Oct. 10, 2014, and in the European Union on Nov. 18, 2014. During that brief period of market availability in fourth-quarter 2014, Harvoni sales registered at an impressive $2.13 billion, placing the drug at No. 51 amongst all Rx medications ranked by full-year 2014 sales.
As of July 2015, more than 180,000 U.S. and EU patients had been treated with Sovaldi or Harvoni. Besides their sibling rivalry, other direct market competition comes from Olysio/Sovriad (simeprevir) via Johnson & Johnson. Including sales from Medivir AB, Olysio/Sovriad’s worldwide sales totaled $2.33 billion during 2014. Olysio is relatively new to the hepatitis games as well, having been approved by U.S. regulators in November 2013 and EU health authorities during May 2014.
Olysio was additionally approved by the U.S. FDA during November 2014 in combination with sofosbuvir for adults with genotype 1 chronic hepatitis C infection as a 12-week treatment for patients without cirrhosis or a 24-week treatment regimen for patients with cirrhosis. During July 2015, J&J unit Janssen Therapeutics announced the U.S. filing of a supplemental NDA for all-oral, once-daily Olysio in combination with Gilead’s sofosbuvir. Janssen is seeking approved labeling to reflect the Phase III OPTIMIST-1 and OPTIMIST-2 studies that evaluated 12 and eight weeks of therapy for treatment-naïve and treatment-experienced genotype 1 CHC adult patients without cirrhosis, and 12 weeks of therapy for treatment-naïve and treatment-experienced genotype 1 CHC adult patients with cirrhosis.
According to J&J, Olysio/Sovriad worldwide sales for first-half 2015 were down 58 percent year-over-year due to the market arrival of competitive hepatitis C products. Global sales declined from $1.19 billion in January-June 2014 to $498 million for first-half 2015.
Further proof that the hepatitis arena is a volatile one due to intense and continually improving new competition was demonstrated by the market performance of Vertex Pharmaceuticals Inc.’s Incivek. Launched in the United States during May 2011, Incivek (telaprevir) went on to produce what at the time was the top-selling Rx drug launch ever. Vertex reported that the protease inhibitor’s sales for May-December 2011 reached about $951 million, peaking in the fourth quarter of that calendar term. But the market entry of the likes of Olysio and Sovaldi dismantled Vertex sales of Incivek, which plummeted from $1.16 billion during 2012 to $24 million for 2014.
Biologics for inflammatory diseases continue to excel
The anti-tumor necrosis factor alpha (TNFa) MAb Remicade ranked No. 3 in global sales during 2014. Composed of the active ingredient infliximab, the biologic therapy generated sales of roughly $9.83 billion worldwide across marketers J&J, Merck & Co., and Mitsubishi Tanabe Pharma Corp. Introduced in the United States during September 1998, Remicade has received FDA approval for Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, and ankylosing spondylitis. Merck markets the medicine in Europe, Russia and Turkey, with Mitsubishi Tanabe handling sales activity in Japan.
First-half 2015 sales for Remicade as reported by J&J totaled $3.27 billion, down from $3.41 billion during the same period one year earlier. The company reported lower 2Q 2015 sales in Europe, reflecting the weakening of the euro, loss of exclusivity in Europe and a change in customer inventory levels. The patents for Remicade in certain European countries lost protection during February 2015. Biosimilar versions have been launched in certain non-U.S. markets, leading to a reduction in sales of Remicade in those markets. This activity was reflected in Merck’s first-half 2015 sales for Remicade, which were down 21 percent year-over-year to $956 million.
U.S. sales for Remicade are expected to remain strong for years to come though due to the expected lack of U.S. biosimilar competition. EvaluatePharma projects the drug will produce U.S. sales of $4.28 billion in 2020 compared to $4.16 billion during 2014.
Another anti-TNF agent that treats inflammatory diseases, Enbrel, reached the U.S. marketplace in November 1998 two months after Remicade. Commercialized globally by Amgen Inc., Pfizer Inc. and Takeda Pharmaceutical Co., Enbrel sales improved from $8.7 billion during 2013 to $8.88 billion for 2014.
Amgen reported Enbrel (etanercept) sales of $2.46 billion for the first two quarters of 2015, compared to $2.23 billion for January-June 2014. Pfizer sales for the biologic outside the United States and Canada dropped from $1.89 billion in the first half of 2014 to $1.58 billion during first six months of 2015.
According to Pfizer reports, Enbrel will lose patent protection and/or market exclusivity in Europe during August 2015 and in Japan during September 2015. EvaluatePharma projects that Enbrel will rank No. 6 in worldwide Rx sales during 2020 at $7.22 billion, with U.S. sales coming in at $4.23 billion.
During June 2015, Merck and Samsung Bioepis Co. announced that pivotal Phase III trials for the investigational biosimilars SB4 (Enbrel/etanercept) and SB2 (Remicade/infliximab) met primary endpoints. SB4 and SB2 showed equivalence to the originator medicines in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. The two companies have a collaboration consisting of five biosimilar candidates, including SB5 (Humira/adalimumab), undergoing late-stage development. Each of the biosimilar candidates are expected to be submitted for approval with health authorities around the world within the next two years.
Biosimilar competition for the world’s leading insulin brand
The sales and units leader amongst anti-diabetes medicines is Lantus, which is marketed around the globe by Sanofi. Lantus generated sales of EUR6.34 billion ($8.44 billion) during 2014, representing 18.8 percent of Sanofi’s consolidated revenue for that year. For first-half 2015, Lantus worldwide sales came in at EUR3.29 billion, down 5.4 percent at constant exchange rates and 9.6 percent on a reported basis versus the January-June 2014 time frame.
Lantus is a long-acting human insulin analog indicated for once-daily subcutaneous administration in treating adult patients with type 2 diabetes mellitus who require basal insulin for controlling hyperglycemia. Lantus is additionally available for adult and pediatric patients aged 2 years for type 1 diabetes mellitus. Marketed in 120-plus countries, the drug is the most studied basal insulin with more than 10 years of clinical evidence in diabetes treatment.
Lantus’ compound patent lost protection in the United States during August 2014, and in Europe and Japan during November 2009. U.S. pediatric regulatory exclusivity for the Lantus compound expired during February 2015. A patent-term extension granted in Japan ended in November 2014. A pediatric extension expired in major European countries in May 2015. Other patents protecting the Lantus formulation and its devices are in litigation and expire between 2023 and 2028.
Eli Lilly and Co. and Boehringer Ingelheim GmbH gained European approval for their biosimilar version of Lantus during September 2014. Abasaglar is the first insulin ever approved through the European Union’s biosimilar pathway. Abasaglar is a basal insulin indicated to treat diabetes in adults, adolescents and children aged 2 years and older. The copycat version, reportedly priced as much as 20 percent less than Lantus, was introduced in some small Eastern European markets during July 2015 and is expected to reach the rest of Europe by the end of this year. The drug is to be promoted under the trade name Basaglar in the United States, but Sanofi has blocked that market arrival through the court system until June 2016.
EvaluatePharma trackers project Lantus global sales of $4.94 billion (including $3 billion in U.S. sales) for 2020, which would represent a nine percent decrease in compound annual growth rate from 2014.
The next-generation version of Lantus, branded as Toujeo, was approved for U.S. marketing on Feb. 25, 2015. The once-a-day long-acting basal insulin improves glycemic control in adults with type 1 and type 2 diabetes. Toujeo is available in a disposable prefilled pen that requires one-third of the injection volume used to deliver the same amount of insulin units as compared to Lantus SoloStar.
Toujeo was approved by the Food and Drug Administration during late February 2015, and EU marketing clearance was granted about two months later. During July 2015, the Ministry of Health, Labor and Welfare in Japan approved the drug under the brand name Lantus XR. Extension studies in Japan demonstrated that in patients treated for 12 months, Toujeo maintained similar blood sugar control with fewer people experiencing night-time low blood sugar events, compared to Lantus. Toujeo was additionally cleared for marketing in Canada during May 2015 and in Australia one month later.