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`Top 200 Medicines — Special Report
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`Andrew
`Humphreys
`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.
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`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.
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`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.
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`Humira leads the pack
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`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.
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`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.
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`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.
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`Also during first-half 2015, AbbVie announced results from VISUAL‑I, a Phase III trial investigating the efficacy and
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`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.
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`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.
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`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.
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`Hepatitis C drugs produce unprecedented launches
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`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.
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`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.
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`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.
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`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.
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`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.
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`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.
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`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.
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`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.
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`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.
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`Biologics for inflammatory diseases continue to excel
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`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.
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`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.
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`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.
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`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.
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`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.
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`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.
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`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.
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`Biosimilar competition for the world’s leading insulin brand
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`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.
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`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.
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`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.
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`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.
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`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.
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`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.
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`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.
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`Copyright
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`© 2015 PharmaLive and Outcomes LLC
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