22nd Annual Report 2013

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Top 100 Biotechnology Companies

Biotech industry growth is bolstered by increased R&D spending, an upswing of approved first-in-class medicines, elevated Wall Street valuations, and continued forging of pipeline alliances with Big Pharma.

The top 100 revenue-generating public biotech companies featured in this annual compilation garnered 2012 revenue of $113.34 billion versus $100.61 billion in the prior year, a 12.7 percent improvement. R&D expenditure for the same 100 companies also rose 12.7 percent, from $26.94 billion during 2011 to $30.38 billion for last year. The employee count for the leading biotechnology players additionally increased year over year, growing 4.1 percent.

The top 10 biotech revenue producers of 2012 each posted sales increases compared to 2011. The 10 companies combined for $93.01 billion in biotech/biopharma revenue in 2012 versus $82.96 billion during the prior calendar term, accounting for 12.1 percent growth. The leading 10 R&D spenders also each increased their expenditures from 2011 to 2012, growing 14.7 percent from a combined $20.77 billion in 2011 to $23.81 billion for last year. The work-force totals for the 10 largest biotech entities also each climbed higher, coming in at a collective 3.9 percent uptick from two years ago to 2012.

Biotech stocks and market caps continue to soar

The valuations of listed biotech companies have recovered to reach heights not seen since before the global financial crisis and economic recession. For full-year 2012, the Nasdaq Biotechnology Index improved by 32 percent compared to the previous calendar term. Also in 2012, the AMEX Biotechnology Index rose 42 percent and the Deutsche Borse AG’s DAXsubsector Biotechnology Index increased 37 percent versus 2011.

The impressive growth has continued through 2013 for companies of all sizes and market values. As of May 17, the Burrill Select Indice was up 34.6 percent versus the end of 2012, the Burrill Large Cap grew 35.4 percent, the Burrill Mid-Cap advanced 23.6 percent, and the Burrill Small Cap rose 18.9 percent since Dec. 31, 2012. According to a Burrill report, the four leading biotech companies – Amgen, Biogen Idec, Gilead Sciences, and Celgene – each ended first-quarter 2013 trading at all-time highs.

Market-cap values for many biotech entities have climbed high during the past year and a half as well. For long-time biotech leader Amgen, the company’s market capitalization grew nearly 30 percent from 2011 to 2012, and another 20 percent from year-end 2012 through late May 2013. After more than tripling in value during 2012 to $16 billion, Regeneron Pharmaceuticals’ market-cap value stood at $25.58 billion as of May 20, 2013. Gilead’s market cap as of that date came in at $84.34 billion, after almost doubling in value during 2012. Gilead’s May 2013 market value was higher than Big Pharma players such as AstraZeneca, Bristol-Myers Squibb, and Eli Lilly.

Additionally, the financing environment for biotech entities has improved compared to previous years, though it remains difficult overall.

M&A biotech activity headlines 2012’s top healthcare industry deals

Three of the four healthcare industry’s largest merger and acquisition deals of 2012 involved biotech players. The largest biotech company to be purchased during the past year was San Diego-based Amylin Pharmaceuticals, a former top 20 revenue generator on Med Ad News’ top public biotechnology company lists. Bristol-Myers Squibb of Princeton, N.J., completed the acquisition of Amylin during August 2012 for $31 per share in cash for an aggregate purchase price of $5.3 billion. The total value of the deal, including Amylin’s net debt and a contractual payment obligation to Eli Lilly of about $1.7 billion, reached $7 billion. Amylin now operates as a wholly owned subsidiary of Bristol-Myers Squibb.

Amylin has been committed to the discovery, development and commercialization of innovative medicines for patients with diabetes and other metabolic diseases. Amylin’s primary concentration has been on the R&D and commercialization of a franchise of GLP-1 agonists for treating type 2 diabetes. That franchise included two type 2 diabetes treatments available in the United States and European Union – Byetta (exenatide) injection and Bydureon (exenatide extended-release for injectable suspension/exenatide 2 mg powder and solvent for prolonged release suspension for injection) – and a life-cycle management pipeline with delivery devices and formulation improvements.

The addition of Amylin’s GLP-1 franchise complements Bristol-Myers Squibb’s diabetes franchise and created a comprehensive disease management platform. BMS in recent years has been undergoing a transformation into a next-generation biopharmaceutical company.

The third-largest industry deal of 2012 involved another multi-billion dollar biopharma company acquisition completed in August 2012: Human Genome Sciences was purchased by pharmaceutical giant GlaxoSmithKline. All outstanding shares of Rockville, Md.-based HGS were acquired for $14.25 per share in cash, amounting to $3.6 billion on an equity basis or $3 billion net of cash and debt. The lead medicine in the HGS portfolio was Benlysta (belimumab), which in March 2011 was the first FDA-approved treatment for lupus in more than 50 years. Pipeline assets included the type 2 diabetes drug albiglutide (awaiting FDA approval) and the atherosclerosis treatment darapladib (U.S. Phase III).

GSK managers said the HGS acquisition was well-aligned with the London company’s long-term strategy of delivering sustainable growth, simplifying GlaxoSmithKline’s business model, enhancing R&D returns and deploying capital with discipline. Through complete ownership of Benlysta, albiglutide and darapladib, GlaxoSmithKline expected to simplify and optimize R&D, commercial and manufacturing operations to advance these products most effectively and efficiently while securing the full potential long-term value of the assets. GlaxoSmithKline anticipated achieving at least $200 million in cost synergies to be fully realized by 2015.

Valued as the fourth-biggest industry transaction of 2012 was Dainippon Sumitomo Pharma’s $2.6 billion purchase of Boston Biomedical. One of Japan’s leading pharma players, Dainippon Sumitomo in April 2012 acquired Boston Biomedical. BBI is a Cambridge, Mass.-based biotech company developing a new generation of targeted cancer therapeutics.

BBI is regarded as an industry leader in the creation of drugs that are designed to target cancer stem cells. CSCs are a sub-population of cancer cells that are highly malignant and are believed to be fundamentally responsible for cancer growth, recurrence, drug-resistance and metastasis. Cancer stem cells are highly resistant to existing chemotherapies and targeted agents. Targeting CSCs represents significant promise for fundamentally advancing cancer treatment. The drug candidates BBI608 and BBI503 may become the first marketed anticancer products in the world targeting cancer stem cells. Dainippon Sumitomo plans to commercialize the two small molecular oral drugs in 2015 or later.

2013 biotech M&A movement

“Nothing like Gilead’s $11bn swoop on Pharmasset at the tail end of 2011 emerged in 2012, so 2013 could well follow as a muted year for multiples,” noted EvaluatePharma’s publishing arm, EP Vantage, in its 2012 Biotech and Pharma Year in Review report. “But with biotech valuations sky high, it is clear that any acquirer will have to be prepared to pay top dollar to access many of the drug developers that investors have become so excited about.”

Top 15 biotech company Elan in May 2013 rejected a revised tender offer from the privately held investment firm Royalty Pharma. According to Elan execs, Royalty Pharma’s revised offer to acquire all of the Dublin, Ireland-based company’s shares for $12.50 per share via its shell subsidiary Echo Pharma Acquisition substantially undervalues Elan. The first offer to acquire all Elan shares for $11.25 was turned down during April 2013.

May was a very busy month for Elan in addition to rejecting the Royalty Pharma revised tender offer. On May 20, the company announced a variety of transactions to transform and advance Elan for years to come. Elan announced the acquisition of AOP Orphan – a private, orphan disease company based in Vienna, Austria – as well as 48 percent of Newbridge Pharmaceuticals – a private Africa, Middle East & Turkey (AfMET) company with headquarters in Dubai, UAE. Elan also revealed the divestment of ELND005 into Speranza Therapeutics – a private and independent Irish company. ELND005 is undergoing clinical development for bipolar, agitation/aggression in Alzheimer’s disease, and Down syndrome. Additionally, Elan announced debt issuance of $800 million to optimize full potential of capital structure and markets, as well as a share repurchase of $200 million – consistent and systematic return of capital to shareholders.

Elan agreed to purchase a participation interest in potential future royalty payments related to four respiratory programs partnered with GlaxoSmithKline on May 13: Relvar Ellipta/Breo Ellipta, Anoro Ellipta, MABA (Bifunctional Muscarinic Antagonist-Beta2 Agonist) monotherapy (GSK961081, or MABA ‘081), and vilanterol (VI) monotherapy. Elan was responsible for a one-time cash payment of $1 billion to Theravance in exchange for a 21 percent participation interest in the potential future royalty payments from the four programs when, as and if received by Theravance.

During early April 2013, Elan announced the closing of the Tysabri (natalizumab) collaboration transaction with Biogen Idec. This deal represented the largest M&A activity for the pharma/biotech arena during first-quarter 2013. Elan gained $3.25 billion in cash and will receive double-digit tiered royalty payments, on all indications, for the life of the complete Tysabri asset. For the first 12 months Elan will receive 12 percent royalties on in-market sales of Tysabri. Then Elan will receive 18 percent royalties on in-market sales up to $2 billion and 25 percent royalties on in-market sales exceeding $2 billion. For 2012, in-market sales of the multiple sclerosis drug amounted to $1.6 billion.

According to Elan, the totality of the strategically driven decisions announced on May 20 along with the Theravance royalty participation deal and dividend pass through as well as the Tysabri transaction, will form a dynamic and unique business foundation for Elan in the years ahead. “Upon approval and closing of this set of transactions (from May 20), the Elan business would be comprised of very high net margin, multi asset and long term revenue streams (within Multiple Sclerosis and Respiratory), an orphan disease platform, and a strong regional commercial presence,” says Elan Chief Financial Officer Nigel Clerkin. “All of these are underpinned by a strong balance sheet as well as a highly efficient and strategically advantageous tax structure.”

The top M&A transaction of first-quarter 2013 was Gilead’s license pact with MacroGenics. MacroGenics is a privately held biotech company that develops next-generation antibody therapeutics. On Jan. 7, the two companies agreed on deal for the development and commercialization of Dual-Affinity Re-Targeting (DART) products directed at up to four undisclosed targets. MacroGenics’ DART technology is a proprietary, bi-specific antibody platform in which a recombinant molecule can target two different antigens.

The DART technology allows for the generation of highly stable antibody-based therapeutics that can simultaneously target two separate antigens. According to MacroGenics, DART therapeutics can accommodate virtually any variable region sequence in a “plug-and-play” fashion. They are highly potent and have very favorable manufacturing properties. DARTs may be engineered with short or extended serum half-life to support different applications in various disease areas. In one particular configuration, the proteins can redirect the body’s cell-destroying, immune effector cells against tumor cells.

MacroGenics has engineered more than 100 different DART proteins developed for internal pipeline programs and external collaborators. The Rockville, Md., venture-backed company intends to file an IND for its first DART product candidate in late 2013.

MacroGenics could receive up to $30 million in license fee payments and an additional $85 million in pre-clinical milestones across the four DART programs. Gilead holds exclusive global rights for three of the programs. For the other, MacroGenics retains development and commercialization rights outside of North America, Europe, Australia and New Zealand, which covers multiple major markets including Japan, China, Korea, Brazil, Russia and others. Gilead will fully fund MacroGenics’ research activities for each program. MacroGenics could receive up to $1 billion in clinical, regulatory and commercialization milestone payments if every program achieves the requisite milestones. MacroGenics may be the recipient of tiered (up to low double-digit) royalties on future net sales.

Gilead completed its acquisition of the drug development company YM Biosciences in February 2013. YM has mainly concentrated on advancing its lead product candidate CYT387, an orally administered inhibitor of the JAK1 and JAK2 kinases. These kinases have been implicated in a variety of hematological and immune cell disorders such as myeloproliferative neoplasms and inflammatory diseases, as well as particular cancers. Gilead landed YM for $2.95 per share in cash, with a transaction value of $510 million.

Shire was the only biotech company to account for a top 10 industry acquisition during the first three months of 2013. Kicking off the year eight days into it, Shire announced a deal to purchase Cambridge, Mass.-based Lotus Tissue Repair. The privately held biotech company has been developing the first protein replacement therapy being investigated for treating dystrophic epidermolysis bullosa. DEB is a devastating orphan disease for which there is no available treatment option other than palliative care.

Lotus Tissue Repair’s ABH001 is an engineered, human fibroblast-derived dermal substitute. ABH001 is generated by culturing human neonatal dermal fibroblasts onto a bioresorbable polyglactin mesh scaffold. The PGLLA mesh serves as the scaffolding onto which fibroblasts are grown; they secrete dermal collagen, other extracellular matrix proteins, growth factors, and cytokines, producing a three-dimensional human tissue containing metabolically active living cells. The final product includes a well-developed dermal matrix and evenly dispersed neonatal dermal fibroblasts.

New potential blockbuster drugs

The biotech industry has produced a variety of first-in-class medicines during 2012 and 2013 that each could generate more than $1 billion in peak annual sales.

Perjeta (pertuzumab) is approved for marketing in the United States and European Union for treating people with HER2-positive metastatic breast cancer who have not received prior therapy for their metastatic disease. The Roche medicine is designed specifically to prevent the HER2 receptor from pairing with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process believed to play a role in tumor growth and survival. Binding of Perjeta to HER2 may additionally signal the body’s immune system to destroy the cancer cells. The combination of Perjeta, the established mega-brand Herceptin and chemotherapy is thought to provide a more comprehensive blockade of HER signalling pathways. Industry analysts have estimated global sales of nearly $2 billion for Perjeta during 2016.

Another Roche medicine recently cleared by U.S. regulators is Kadcyla (trastuzumab emtansine or T-DM1). This is the first FDA-approved antibody-drug conjugate (ADC) for the treatment of HER2-positive mBC, an aggressive form of the disease. An ADC is a new type of targeted cancer medicine that can attach to certain forms of cancer cells and deliver chemotherapy directly to them. The drug consists of the antibody trastuzumab and the chemotherapy DM1, which are combined using a stable linker. Kadcyla unites the mechanisms of action of trastuzumab and DM1. This is the first ADC to result from Roche and Genentech’s 30 years of HER2 pathway research and the third medicine Roche has developed for the treatment of HER2-positive breast cancer.

Similar to Herceptin, Kadcyla binds to HER2-positive cells and is believed to block out-of-control signals that make the cancer grow while calling on the body’s immune system to attack the cancer cells. Once Kadcyla is taken up by those cells, the drug is designed to destroy them by releasing the DM1 inside the cells.Roche licenses technology for Kadcyla via a deal with ImmunoGen. EvaluatePharma analysts have projected 2018 global sales of $1.65 billion for the anti-HER2 (ErbB-2) MAb-DM1 maytansinoid conjugate.

Xeljanz (tofacitinib) is a novel medicine marketed by Pfizer for the treatment of rheumatoid arthritis. The drug is available in the United States, Japan and Russia for treating adults with moderate-to-severe active rheumatoid arthritis with previous treatment history. Xeljanz is the first approved RA treatment in a new class of drugs called Janus kinase (JAK) inhibitors.

Ariad Pharmaceuticals’ kinase inhibitor Iclusig (ponatinib) was cleared for marketing by FDA in December 2012 via an accelerated approval process. The new medicine is indicated for treating adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia that is resistant or intolerant to prior tyrosine kinase inhibitor therapy. Iclusig represents the first medicine to reach the marketplace for Ariad, a worldwide oncology company concentrated on the discovery, development and commercialization of cancer drugs.

Iclusig could reach yearly sales of $800 million for patients for whom previous treatments have failed, and that sales amount could nearly double with approval of additional use against new cases. Iclusig is also being studied in clinical development by Ariad for newly diagnosed chronic myeloid leukemia, lung cancer (FGFR), AML (FLT3), gastrointestinal stromal tumors (C-KIT), and lung cancer (RET).

Biotech entity Vertex Pharmaceuticals received the green light from U.S. regulators at the end of January 2012 for Kalydeco (ivacaftor). The chemical-based, non-biotech drug is indicated for treating cystic fibrosis in patients 6 years old or older with the G551D mutation in the CFTR gene. This product represents a breakthrough therapy for cystic fibrosis because the already-existing therapies only treat the symptoms of this genetic disease.

Kalydeco sales for 2012 totaled $172 million. During January 2013, Kalydeco gained FDA Breakthrough Therapy Designations for: monotherapy for potential additional indications beyond the current approval for CF patients 6 and older with the G551D mutation; and in combination therapy with lumacaftor (product code VX-809). Vertex’s CFTR corrector lumacaftor is undergoing Phase II trials for the treatment of cystic fibrosis. Industry analysts have projected 2016 worldwide Kalydeco sales of more than $1 billion.

Tecfidera (dimethyl fumarate) is another chemical-based entity that was developed and is marketed by a biotech powerhouse. Tecfidera is manufactured by Biogen Idec of Weston, Mass., in capsule form. The drug may decrease a person’s white blood cell count (lymphocytes). Lymphocytes aid in protecting the body from infection and low counts can raise the risk of infection, although no significant increase in infections was evident in patients taking Tecfidera in clinical studies.

The immunomodulator gained U.S. regulatory clearance during late March 2013 for the treatment of relapsing-remitting multiple sclerosis and was launched shortly thereafter. The new first-line oral treatment has been clinically proven to significantly reduce important measures of disease activity, including relapses and development of brain lesions. The drug also has been demonstrated to slow disability progression over time, while showing a favorable safety and tolerability profile. Impressive late-stage data revealed that Tecfidera could cut the yearly multiple sclerosis relapse rate by about half. The twice-daily dosage was associated with a decrease in new or expanded lesions by 71 percent to 99 percent, with a 38 percent reduction in progression to disability.

Tecfidera is undergoing regulatory review by health authorities in Australia, Canada and Switzerland. On March 22, 2013, the Committee for Medicinal Products for Human Use issued a positive opinion recommending that the European Commission provide marketing authorization for the drug in the European Union as a first-line oral treatment for adults with RRMS. The European Commission decision is anticipated during second-quarter 2013. Backed by recently granted 15-year U.S. and EU patent protection lasting until 2028, more than $3 billion in sales on an annual basis are projected for Tecfidera.

Another potential blockbuster for Biogen Idec – this one of biotech nature – is Plegridy (peginterferon beta-1a). The pegylated subcutaneous injectable candidate for relapsing forms of multiple sclerosis (RMS) is awaiting FDA clearance as of May 2013. Plegridy represents a new-generation version of Biogen Idec’s long-standing blockbuster MS medicine, the glycoprotein Avonex (interferon beta-1a).

The U.S. regulatory filing for Plegridy was based on the results from the first year of the two-year worldwide Phase III ADVANCE study. The data showed that the drug met all primary and secondary endpoints by significantly reducing disease activity such as relapses, disability progression and brain lesions versus placebo. The new molecular entity additionally demonstrated favorable safety and tolerability profiles at one year.

With Plegridy, interferon beta-1a is pegylated to extend its half-life and prolong its exposure in the body, allowing for study of a less frequent dosing schedule. “We believe that based on the efficacy and safety Plegridy has demonstrated, in addition to its less frequent dosing schedule, it has the potential to become a preferred interferon treatment option,” stated Douglas E. Williams, Ph.D., Biogen Idec’s executive vice president of Research and Development.

As of late May 2013, Biogen Idec intended to file a Marketing Authorization Application (MAA) for Plegridy to the European Medicines Agency within the coming weeks.

Approved by FDA in August 2012, the HIV medicine Stribild has been predicted to approach $3 billion in 2018 global sales. Marketed by Gilead, the complete once-daily single tablet regimen is intended for HIV-1 infection for treatment-naïve adults. Stribild unites four drug compounds in one daily tablet: the integrase inhibitor elvitegravir, the pharmacoenhancing agent cobicistat, and the nucleoside analog reverse transcriptase inhibitors emtricitabine and tenofovir disoproxil fumarate.

Near-term prospects emerging from the pipeline

The U.S. Food and Drug Administration approved for marketing about 40 novel biologic or small-molecule agents during 2012. Last year represented the highest amount of FDA approvals for novel drugs since 1997. More than half of the 2012 approvals were marked by FDA priority review or orphan drug designations.

One of the most-anticipated new product launches in 2013 could be BioMarin Pharmaceuticals’ BMN-110 for MPS IVA (Morquio A Syndrome). The inherited, autosomal recessive disease results from a deficiency of a particular lysosomal enzyme, N-acetylgalactosamine-6 sulfatase (GALNS). Deficiency of the enzyme leads to excessive lysosomal storage of keratan sulfate in many tissues and organs. This accumulation causes systemic skeletal dysplasia, short stature and joint abnormalities, which restrict mobility and endurance. Thorax malformation impairs respiratory function, and malformation of neck vertebrae and ligament weakness results in cervical spinal instability and potentially cord compression. Other symptoms can consist of hearing loss, corneal clouding, and heart valve disease.

BMN-110 is enzyme replacement of GALNS, which is anticipated to result in clearance of keratan sulfate from the lysosome. As a result, progression of the disease would be halted and may lead to amelioration of some symptoms.

“There are only about 3,000 patients diagnosed with the rare lysosomal storage disorder Mucopolysaccharidosis Type IVA, also called Morquio A Syndrome” notes analysis from FierceBiotech. “The condition, the result of an enzyme deficiency, triggers a host of skeletal and bone disorders. But a number of drug developers in the rare disease area have proven time and again that a successful enzyme replacement drug that can control these conditions can earn a significant amount of revenue, with payers of every stripe willing to foot huge bills for these treatments.”

As mentioned earlier in this article, albiglutide is a glucagon-like peptide-1 receptor agonist awaiting FDA approval for the treatment of type 2 diabetes. GlaxoSmithKline announced the U.S. regulatory filing for the investigational once-weekly subcutaneous treatment in January 2013 and the EU submission two months later. The biological drug was previously developed by Human Genome Sciences, which was acquired by London’s GlaxoSmithKline.

GLP-1 is a peptide normally secreted from the gastrointestinal tract during a meal, which in turn aids in the release of insulin to control blood sugar elevations after eating. For individuals with type 2 diabetes, GLP-1 secretion in response to a meal is reduced or absent. GLP-1 is quickly degraded while albiglutide has been developed to have a longer duration of action by comprising two copies of modified human GLP-1 fused in series to human albumin.

Though not a first-in-class medicine and it will be joining a crowded diabetes marketplace if approved, albiglutide does represent yearly billion-dollar sales potential.

Pharma power Sanofi is seeking global marketing approval of Lemtrada (alemtuzumab) for treating multiple sclerosis. The monoclonal antibody selectively targets CD52, which is a protein abundant on T and B cells. Treatment with alemtuzumab leads to the depletion of circulating T and B cells that are believed to be responsible for the damaging inflammatory process in multiple sclerosis. Alemtuzumab has minimal effect on other immune cells. The acute anti-inflammatory effect of the drug is immediately ensued by the onset of a distinctive pattern of T and B cell repopulation that continues over time. This process rebalances the immune system in a way that potentially reduces MS disease activity.

Alemtuzumab came to Sanofi through its acquisition of Genzyme, which maintains the global rights to alemtuzumab. Genzyme holds primary responsibility for the drug compound’s development and commercialization in multiple sclerosis. Bayer HealthCare retains an option to jointly promote alemtuzumab in MS, which the German company plans to carry out. Upon regulatory approval and marketing, Bayer would receive contingent payments based on sales revenue.

Methodology

To be included in this biotechnology report, companies have to be publicly traded; have to research and develop human therapeutics deriving from a naturally occurring substance or a biological substance – either human, animal, or plant; have to apply genetic engineering or recombinant DNA technology; and their therapeutic products have to be intended for sale through prescription.

Companies considered for this report are involved in genetic technology, molecular biology, structural chemistry, and/or rational drug design. In addition to researching and developing human therapeutic products, some companies market therapeutic products and others market diagnostic and agricultural products. Excluded from this report are companies that are dedicated entirely to developing assay technologies, high-throughput screening technologies, biotechnology testing equipment, or naturally derived OTC products.

The companies included in this special report have been ranked based on revenue generated in calendar-year 2012 or fiscal-year 2012.

To be considered for the rankings, companies must publish their financial information. For companies reporting on a fiscal year, available figures from the most-recent fiscal year as of this magazine’s press time are used. Companies that were successfully acquired during calendar-year 2012 are excluded from this year’s rankings. The information in this report was gathered from company-provided documents, including annual rep)orts, Form 10-Ks, quarterly reports, and press releases.

For biotech companies with non-U.S. headquarters, Med Ad News used year-end average exchange rates listed by the Federal Reserve Board to convert financial figures to U.S. dollars. The conversions were made for the purposes of convenience and comparison only.

So that the percentage changes in financial information reflects the actual increase or decrease in the company’s home-country currency, Med Ad News used a constant rate of exchange for 2012 and 2011, reflecting the increase or decrease reported by the non-U.S. company.

For certain non-U.S. companies that reported financial figures in U.S. dollars, those figures may have been used by Med Ad News editors rather than the year-end average exchange rates from the Federal Reserve Board to convert local currencies.