“The elite of the Americas”, “The European giant” and “The Indian God” seem to have become the must-haves for the big names in the US generic market today, but there is also a mysterious visitor from the desert behind the strongest teams.
The audacious Arab world’s big brother Hikma, with his Baxford Sword and Roxward Shield, set off a strong West Asia whirlwind in a bloody, exotic world and successfully interpreted the Middle Eastern version of the ambitious event. Perhaps the blade has not yet been invincible, and perhaps the Aegis is not as strong as a rock. However, Hikma has never stopped on the persistent and relentless rise.
Founded in 1978 in Amman, Jordan, Hikma currently has more than 8,000 employees, 29 production sites in 11 countries, and 6 R&D centers. It is the pharmaceutical company with the 5th largest market share in the Middle East and North Africa (2015 market share). About 4%, the top four are Sanofi, Novartis, GSK, and Pfizer, respectively).
The company is mainly engaged in R&D, production and sales of generic pharmaceutical products and provides partial contract processing services. Its business scope covers more than 50 countries around the world, mainly in the Middle East and North Africa, the United States, and Europe. It is divided into brand drugs, injections and generic drugs. The three major modules.
The brand drug module is responsible for selling branded generic drugs and some patented drugs that are authorized for introduction in the Middle East and North Africa and other emerging countries; injection module is responsible for the worldwide sales of injection generic drugs; the generic module is responsible for other dosage forms other than injections in the U.S. market Sales.
The U.S. market business is mainly operated by Westward, its subsidiary in Eatontown, New Jersey. After completing the acquisition of Bedford and Roxane in the last two years, it has become the sixth largest generic pharmaceutical company in the United States (by sales) and the third largest. Injection generic company (in terms of sales volume).
From 1996 to 2014, Hikma’s global income maintained a sustained growth trend, with a compound growth rate of 18% in the past five years. In 2015, Hikma’s global sales revenue was US$1.44 billion, a decrease of 3.3% over the previous year (eg, at a constant exchange rate, which represents a 1.7% increase over the previous year). The revenues of branded drugs, injections, and generics were 5.7, respectively. Billion dollars, 710 million dollars and 151 million dollars, accounting for 40%, 49% and 10%, respectively.
From a regional perspective, in 2015, the US market sales revenue was 697 million U.S. dollars, accounting for 48% of the company’s total revenue. The Middle East and North Africa market sales revenue was 656 million U.S. dollars, accounting for 46%. The sales revenue in Europe and other countries was US$87 million, accounting for only 6%.
In the first half of 2016, Hikma’s global sales revenue was US$882 million, an increase of 24.4% compared to the same period of last year. Revenues of branded drugs, injections and generic drugs were US$264 million, US$357 million and US$257 million, respectively. It is 30%, 40% and 30% respectively.
From a regional perspective, US market sales revenue was US$529 million, which accounted for 60% of the company’s total revenue. Market sales revenue in the Middle East and North Africa was US$304 million, accounting for 34%, and European and other countries’ market sales revenue was US$49 million. The dollar, accounting for 6%. The incorporation of Roxane has resulted in a significant increase in revenue for both the generics module and the U.S. market. It is expected that revenue for 2016 will be around US$2 billion.
a. Generic drugs
The generic part of Hikma’s US market mainly includes the U.S. portion of its global injection module and the generic drug module.
As of the end of June 2016, Hikma’s sales of generic products in the US market included 163 chemical molecules and compound combinations, of which 134 were single dosage forms and the remaining 29 contained two or more dosage forms.
From the dosage form, there are 77 tablets, 62 injections, 22 oral liquids, 20 capsules, 10 suspensions, 4 nasal sprays, 2 drops, 1 surface solution, and 1 lozenge tablet. The two major dosage forms of injection and injection were 40% and 32%, respectively.
From the sales point of view, there are 3 molecules 15 years of sales exceeded 100 million U.S. dollars, 41 molecules have 15 years of sales between 10 million and 110 million U.S. dollars, and 71 molecules have 15 years of sales of 1 million. Between 10 million US dollars. In 2015, 17 molecules sold in products were no longer sold in 2016.
It is estimated that the market size of global injection generic drugs will exceed 70 billion U.S. dollars by 2020, and the compound growth rate between 2013 and 2020 will be around 10%. A series of brand injection products with a total sales volume of US$15 billion will lose patent protection between 2015-2018.
From 2011 to 2015, the U.S. injection market continued to expand and the compound growth rate was close to 5%. In 2015, the size of the U.S. injection market was US$133.6 billion (not included in biological, insulin, and hormonal products), of which generic injections were generic drugs. Nearly 9 billion U.S. dollars is expected to continue to grow at an annual rate of 6% in the coming years.
In recent years, both Hikma and U.S. injections have maintained a growth trend. In 2015, Hikma’s injection revenue in the U.S. market was 546 million U.S. dollars, accounting for nearly 80% of its global injection revenue.
The expansion of Hikma’s U.S. injection business began with the acquisition of the Baxter injection generic drug module in 2010 and was further strengthened through the acquisition of Bedford in 2014 (see the section on “M&A”).
At present, Hikma’s US injection module strategy is to continue to promote the transfer and integration of income Bedford products, through the re-listing of the part of the product and newly approved products continue to optimize the existing product line; on the other hand through its own research and development to accelerate the pre-installed New packaging forms, large quantities of out-of-stock products, and complex injections with multiple barriers.
In addition to its original products that were sold and pending approval in the city, more than 40 of the suspensions of the acquisition of Bedford products have been transferred to three other bases in the United States and Europe, and they are planned to be listed on the market in 2015-2017. 20.
As of June 2016, Hikma accounted for 12.3% and 5.3% of the volume of sales and sales of the generic pharmaceutical injection market in the United States. Ranked third in sales, behind hospira (36.7%) and APP (13.5%); ranked sixth in sales, ranked in hospira (19.1%), APP (13.3%), Sandoz (8.7% ), Mylan (5.7%) and Teva (5.5%) afterwards. In 2011, Hikma ranked second and fourth in terms of sales volume and sales share respectively. The decline in rankings also reflected the increasingly fierce competition in the injection market.
From the perspective of sales channels, nearly 90% of Hikma’s US injection products are sold through the GPO channel represented by Novation, 8% through the wholesaler channel represented by TOP3, and the remaining 2% directly into the hospital network.
The good relationship with each channel greatly promotes the sales of Hikma injection products.
In 2011, Hikma’s strength in non-injection generics in the United States was still relatively weak. At that time, only 50 approved products containing 122 specifications were used, and almost all were ordinary tablets and capsules produced by West-Ward Base Camp. There are only 405 people.
The integration of Roxane in 2015 has enabled Hikma’s strength in this area to grow by leaps and bounds. The number of employees and the number of approved products have grown to 1,454 persons and 107 (including 357 specifications), and they have entered the ranks of non-injection generic drugs TOP10. .
The acquisition of Roxane’s former Hikma’s non-injectives consisted of ordinary oral solid preparations. The incorporation of Roxane products brought a variety of other non-injectable formulations such as oral liquids, sprays, and suspensions, which enriched and improved Hikma’s non-injections. Product line, while increasing the product type and quantity, it is more important to obtain matching R&D and production capabilities accordingly.
Roxane’s pending approval and R&D product line includes a number of differentiated products that contain technology and drug-governance barriers, of which patent-challenged products account for a significant portion of the total.
In the future, Hikma’s strategy in the non-injection field will continue to follow Roxane’s previous idea. It will use its current R&D team and facilities to develop a differentiated product group that includes patent-challenged products, and further develops itself through acquisitions and acquisitions. Fill gaps in existing product areas and dosage forms, improve product development efficiency, and introduce more new products in the shortest time.
b. NDA brand drugs
As of June 2016, Hikma had a total of 7 NDA brand drugs in the city’s products. Except Mitigare, the rest of the products were approved 2,000 years ago.
From the dosage form, 5 out of 7 products are injections, and one tablet and one capsule; from the NDA category, including a new chemical entity NDA and new dosage forms, etc. 505(b)(2) NDA.
In terms of sales, only two products with annual sales of more than 2 million have very limited profits. ROBINUL and ROXICET, two NDA products with sales of only a few thousand US dollars in 2015, are no longer sold in 2016, and it is expected that there will continue to be withdrawal of limited-profit NDA products in succession.
Hikma has 29 production sites in 11 countries in the world, of which 21 are located in the Middle East and North Africa and the remaining bases are in the United States, Italy, Portugal and Germany. Reasonable distribution and strong production capacity ensure good product supply in all regional markets around the world.
The three US production sites are located in Eatontown, New Jersey, Cherry Hill, and Columbus, Ohio. The Eatontown base (304,000 square feet) and the Cherry Hill base (378,000 square feet) are responsible for oral solid preparations, respectively. (tablets and capsules) and the production of sterile injections, and the Columbus base (1 million square feet) obtained through the acquisition of Roxane is larger in terms of productivity and coverage, and has oral liquids in addition to oral solid preparations. The ability to produce a variety of other dosage forms such as inhalers.
In addition to the above three production bases, Hikma also owns a distribution center in Memphis, Tennessee, acquired through the acquisition of the Baxter injection generics business. It is also the only distribution center in the United States and plays a major role in its product supply chain. In May 2015, Hikma leased a site adjacent to the site for the expansion of the transit warehouse scale. The total area of the distribution center has reached 150,000 square feet.
Taking into account factors such as production costs and production capacity, Hikma is also actively producing products for the US market in other regions outside the United States. In addition to the United States’ three production bases, production bases in Jordan, Saudi Arabia, Portugal, and Germany also passed FDA inspections and assumed the tasks of supporting production in some US market products, of which Germany and Portugal’s production bases are mainly used for anti-tumor. Production of cephalosporins and injections, while production sites in Saudi Arabia and Jordan are mainly used for the production of non-injectable products.
The Eatontown and Portugal bases in the United States received FDA warning letters for GMP issues in 2012 and 2014, respectively, and have been successfully resolved. Many out-of-stock conditions in the U.S. market are actually caused by the suspension of production by major suppliers due to the warning letter. Out-of-stock caused by non-compliance of production of plants and products accounted for nearly 70% of all out-of-stock, relative to the number of competitors. The field of less injections is particularly evident.
In recent years, with the FDA’s efforts in many aspects such as pre-notification of drug companies, most of the FDA’s shortages were reported in advance to avoid success, and the number of FDA officially released stocks showed a declining trend. In 2015, the FDA issued a total of 26 out-of-stock notifications, of which 15 were injections, which accounted for 57% of all products, and this figure was 73%, 72%, 80%, and 68 respectively in the four years from 2011 to 2014. %.
The phenomenon of out-of-stock is unfavorable to public health benefits, but it is also a rare opportunity for some pharmaceutical companies on the other. It is of great significance to use the period of time when competitors are out of stock to expand their advantages or reduce the gap before.
Hikma performed particularly well in this area, taking targeted measures to seize opportunities on the basis of active research on the dynamics of stock-outs. Eurohealth, a Portuguese subsidiary responsible for the production of some of its US injection products, received FDA-sold out of stock in 2016. The aid award has become one of the three companies that have so far won the award.
Research and development
Hikma has seven R&D centers worldwide, located in the United States, the Middle East and North Africa. The two R&D centers in the United States are located in Bedford, Ohio and Columbus.
The Bedford Research Center (100,000 square feet) was acquired through the acquisition of the Ben Venue site in 2014 and currently has more than 40 R&D personnel. It is mainly used for the research and development of Hikma’s US market for aseptic injection products; Columbus R&D Center passed 2015 The acquisition of Roxane has obtained more than 180 R&D personnel, mainly for the research and development of Hikma’s non-injector generics in the US market.
In the injection module, as of September 2016, Hikma’s follow-up product line consists of 43 products awaiting approval and 91 products in the R&D process, from the level of differentiation (patent-challenged products, complex processes, difficulties in procurement of bulk drugs, etc. In terms of one level each), 95% of products have at least one level, and about half of them are antitumor products.
In the non-injection module, as of October 2016, Hikma’s follow-up product line consists of 25 pending approval products (17 patent-challenged products) and 71 products under development (32 patent-challenged products, of which 22 Owns the first filing opportunity).
From the perspective of differentiated levels, all 96 products have at least one level; from the product type, 25 products are high protection measures, 12 are control products, 11 are controlled release products, and 11 are Submit products to FDA for risk assessment requirements.
In addition to its own R&D, Hikma is also actively seeking new product listing opportunities in the U.S. market through cooperation with R&D partners such as Skyepharma. Apart from R&D, it has acquired and licensed generic ANDA (especially differentiated products) generic drugs. The introduction is also an important part of its strategy to increase product quantity.
Before the completion of the Roxane acquisition in 2015, Hikma’s annual R&D investment was US$36 million, accounting for less than 3% of the Group’s total revenue. After the acquisition of Roxane, the total R&D expenditure in the first half of 2016 was US$57 million, which was in the Group’s total revenue. Accounting for 6%.
Roxane is also a good player in patent litigation based on its strong patent-challenge product R&D capabilities. The acquisition by Hikma is a good complement to Hikma’s relatively weak strength in the field of patent challenges.
Statistics on the Newport database are summarized. At present, the cumulative number of patent challenges ANDA in Hikma’s name has reached 53, of which Roxane has contributed 42 and 4 out of 11 have been acquired from the Bedford business. The other 7 have come from before. Hikma’s own submission before acquiring Bedford and Roxane.
From the point of patent challenge product formulations, oral solid preparations accounted for 74% of all products. Among all 53 products, there were 33 tablets and 6 capsules, followed by injections, suspensions and oral solutions. Below 6; From the number of competitors that challenge the same product for patents, 70% of products are between 0-9, 45% of products are under 5, of which 4 are exclusive challenges, and overall competition is lower than average. .
From the dosage form, there are 2 tablets, 6 injections, 3 capsules, and 1 suspension; from the perspective of treatment, they are distributed in many places such as anti-tumor, cardiovascular and anti-infection, and are relatively scattered, with no obvious advantages. field.
In terms of sales, the highest performing Alosetron hydrochloride tablets have annual sales of nearly US$20 million, aspirin dipyridamole sustained-release capsules also exceed US$10 million, and the remaining products are between tens of thousands to millions. Wait. The products listed in 2015 have already exceeded 3 million US dollars in the first half of 2016.
M & A
Hikma’s American road is also a merger and acquisition road. Through four clear and well-defined moves on Westward, Baxter “multi-source”, Bedford, and Roxane, Hikma has become a professional leader from the beginning to the next, and later becomes a professional leader. Big rivers and lakes.
If we summarize the entire process, it should be “a keen insight, decisive action, gradual and orderly action, clear goals, and freedom of action.” The simple and clear process is worth learning and drawing lessons from.
Like other foreign might, the newly arrived King of the Middle East generic medicine will inevitably need to find a local younger brother to attend class. In 1991, Hikma smashed West-ward’s revenue due to a narrow range of products in a loss crisis, as a stepping stone to open the door to the US generic market. Through the reorganization of the company and the implementation of a series of effective management measures, West-ward’s operating conditions gradually improved in the late 1990s and further expanded its scale through several expansions in 1995-2005. As an American spokesperson for Hikma, West-ward is solely responsible for the specific operations and operations of Hikma in the US market, covering the entire industrial chain including R&D, production and sales. After the acquisition of Bedford and Roxane businesses in recent years The strength of West-ward has been further strengthened and has now become the largest contributor to the overall performance of Hikma.
In October 2010, injection giant Baxter sold its US injection generic drug module “multi-source” to Hikma for US$112 million. Baxter’s move is mainly aimed at concentrating superior resources into its more value-added patented product business, so as to better implement its differentiated product strategy. Through this acquisition, Hikma obtained a total of 41 injection products including various controlled products, Chery Hill injections production base in New Jersey and a warehouse and distribution center in Memphis, Tennessee, from the US injection market ten The younger brother who has opened up has become the second largest brand in the overall sales volume of more than 15%, second only to Hospira. He successfully performed the perfect counterattack for foreign residents.
All 41 products are either Ampoules or vials of injections, covering more than 150 specifications and 23 therapeutic areas. In 2009, the company’s overall sales were US$170 million. Hikma’s US market operations and global injection business have thus doubled and are under control. The share of injections has also risen to second place behind Hospira.
In addition to the rich product line’s contribution in sales, another major significance of this acquisition is to enable Hikma to obtain the ability to produce injections in the United States, laying a preliminary foundation for its US injection business. The acquisition includes 41 generic products covering the vast majority of Baxter’s original “multi-source” modules, but Baxter still retains 6 products such as cyclophosphamide for injection. In response to the principle of fair competition, Hikma transferred two injectable products, phenytoin and promethazine hydrochloride, to X-Gen, a generic pharmaceutical company based in New York, at the request of the Federal Trade Commission.
Ben Venue is a subsidiary of German pharmaceutical giant Boehringer Ingelheim (BI) in the United States. In addition to operating its own injections, it also undertakes the production of some contract processing projects. It has a large-scale injection production base in Bedford, Ohio. It consists of four injection production plants and a quality R&D center.
In August 2011, the Canadian Food and Drug Administration issued an announcement that it believes Ben Venue’s Bedford base has a series of problems that do not comply with GMP. It will temporarily suspend the use of the remaining drugs other than those used for serious diseases. import. Subsequently, the FDA conducted an on-site inspection of the Bedford site and found many problems, causing the base to suspend production and rectification in November 2011.
In the following two years, BI invested US$350 million to improve the venue, but it was not effective. Then if the pre-judgment continues, it will lose 700 million U.S. dollars in the next five years. After comprehensive consideration, BI announced that it will shut down the base in 2013 and gradually start layoffs in 2014.
At the critical moment, two lawmakers from Ohio, Sherrod Brown and Marcia Fudge, stood and actively urged BI to seek buyers for Bedford as soon as possible. On the other hand, they communicated with the FDA to seek temporary approval for some serious diseases. Key production licenses for out-of-stock drugs.
Hard work pays off, and both have quickly achieved results: In March 2014, the FDA approved Ben Venue to manufacture the out-of-stock anti-tumor product doxorubicin; in May 2014, Hikma and Ben Venue reached an agreement of 300 million. The U.S. dollar first acquired the U.S. injection generic drug business operated by its subsidiary Bedford Laboratories, including existing products (84 approved products, 16 pending products, and 11 R&D products), related intellectual property, stock materials, and drugs involved. Government, sales, BD and other multi-sector employees. From the therapeutic perspective, anti-cancer products accounted for more than half of the products approved for this acquisition, followed by anti-infective, cardiovascular, anesthetic, and labor pains.
In July 2014, Hikma agreed to continue to acquire Ben Venue Bedford Base and complete the acquisition in September. Through this acquisition, Hikma has successfully surpassed Fresenius and Hospira in number of approved generic injection products in the United States. Injection pipelines, production and R&D capabilities have been further enhanced after the acquisition of Baxter injection generics business. In the next three years, it will first re-list about 20 Bedford products that had been discontinued at the time.
At the time, Hikma had two FDA-inspected bases in Portugal and Germany in addition to the Cherry Hill production base in the United States. The production capacity of its own injections was already adequate. In addition to the production base at Ben Venue, the quality R&D center of the pilot plant was included. The other four factories outside that part actually have a general interest and have no plans to regroup. After completing the acquisition, Hikma gradually transferred some of the major equipment from Bedford’s products and production bases to the above-mentioned other existing production bases. The Bedford Base has been stagnating until it was acquired by the award-winning Danish drug company Xellia. Buy at the end of 2015.
In addition to harvesting products, equipment, and research and development, Hikma also established a good relationship with BI through this acquisition, laying the foundation for the subsequent acquisition of BI’s Roxane. While once again sighing with the importance of product quality for pharmaceutical companies, the efforts of the two US congressmen for public interest are also worthy of praise. In response to the principle of fair competition, Hikma transferred five injections of acyclovir sodium, diltiazem hydrochloride, famotidine, chlorphenazine ethanedisulfonate, and sodium valproate to the Federal Trade Commission. Amphastar, a generic pharmaceutical company based in California.
After the acquisition of Bedford, Hikma has already had strong strength in the field of generic injections for injections in the United States, but it is still difficult to shake up the positions of Fresenius and Hospira in the short term. Hikma, who is lofty, still hopes to further enhance the company’s imitation in the United States. The strength of the pharmaceutical market, it is natural to strengthen the non-injector generic module as the next move. Just at this time, Roxane was put on the shelf by German brother BI.
Originally known as Columbus, Roxane was founded in 1885. It is a United States-based generic pharmaceutical company that integrates R&D, production, and sales. In 1978, it was acquired by BI as its US generic module and changed its name to Roxane. Although Roxane was not yet a giant level, he was also a master around the TOP10.
Seen from the product line, Roxane features differentiated generic products, 88 products are sold, covering a variety of non-injectable formulations such as slow-release solid formulations, nasal sprays, and oral liquids, of which 75% are competitors. 3 or less, 80% of the products contain at least one level of differentiation barriers, 90% of the products have the top three market share.
From the perspective of R&D and drug administration, Roxane has a research and development team of more than 180 people and a follow-up product line of 89 products. It is also a good player in the field of patent challenges. Thirty-two out of 89 products have been declared, of which 24 are patent-challenged products. Of the 57 products in the research, 33 are patent-challenged products, with an average of 8 applications each year and 9 new products on the market.
From a production perspective, Roxane has a 875,000-square-foot base in Columbus, with sufficient production capacity to support self-produced multiple non-injection formulations. There have been no critical defects and warning letters in the official audit history of the past 10 years.
In the face of such a good target, Hikma quickly reached an agreement with BI in the form of “1.18 billion US dollars in cash + stocks.” Roxane greatly enhanced the strength of Hikma in the field of non-injection, and the combined Hikma stepped into the ranks of the top 10 giants of generic drugs in the United States. The comprehensive level achieved a qualitative leap.
The good relationship with BI supports this healthy acquisition, and even now there are many American generic drugs, rivers and lakes, even if there is no Teva “I am the rich” domineering or Sandoz “My dad is rich” luck, can have A reliable affluent brother is also very gratifying, after all, many times the key moments are always good.
In response to the principle of fair competition, Hikma transferred two products: prednisone tablets and lithium carbonate capsules to Renaissance, a Pennsylvania-based pharmaceutical company, at the request of the Federal Trade Commission, and returned the commercial sales rights of fluocinamide tablets to The Indian partner Unimark.
Establish a good cooperative relationship with customers, pay close attention to market trends and needs, and strive to promote the rapid launch of high value-added products.
Through internal R&D, joint development, and mergers and acquisitions, we will continue to expand our existing product lines, differentiate differentiated products as future development priorities, develop non-injector generic drugs at the same time as consolidating the advantages of injections, and continue to increase our overall strength.
Through continuous investment, we accelerated development, strengthened the maintenance and improvement of existing plant facilities, and gradually expanded our production scale through new construction and acquisitions. At the same time, we increased investment in R&D and used Roaxne as an opportunity to rapidly increase our research and development level.
Improve production efficiency, while ensuring quality and speed, strictly control costs and expenses, and maximize profits.
Pay attention to personnel training, strengthen training, and build a high-quality, high-level professional team.
As the only Middle Eastern manufacturer in the United States generic drug giant, Hikma has been working on this land for more than 20 years. Since the acquisition of the Baxter injection generic drug business in 2010, Hikma has gradually started accelerating mode, through its own development combined with strategic mergers and acquisitions. In six years, it has achieved stability and counterattacks.
After acquiring Roxane, Hikma has perfected the layout of non-injectives based on the early start of injections, and quickly improved its overall strength while developing more balanced.
However, in the ranks of the giants must also see the current fierce and cruel competition in the US generic market, after Top3 each master show their supernatural powers, but at present there is no absolute strength to completely suppress the strong.
For Hikma, its strength in the field of injections is undoubted, but it is still more to the point than volume, and it is not dominant in overall sales. With the lowering of the threshold for injections, many pharmaceutical companies represented by Dr Reddy have achieved rapid development in this field with low-cost strategies, and continuously narrowed the gap with the traditional injection giants, while the gap between Hikma and Hospira and Fresenius remains the same. It’s not small, it’s hard to shake with current strength.
The grim situation with strong enemies before and after the pursuit of soldiers also put forward higher requirements for Hikma’s subsequent development in the field of injections. In the more competitive non-injection field, Roxane’s incorporation is not enough to make Hikma sit back and relax. In the top ten, Hikma also faces the chase of rivals from nearly ten players behind him.
Hikma’s current differentiated product strategy guarantees its own follow-up competitiveness to a certain extent. However, the strategy still has a lot of room for improvement in the application of injection product lines. At the same time, as differentiation continues to be a trend, this kind of competition The advantages are also bound to be weakened. It will be particularly important for Hikma to increase the added value of follow-up product lines, especially injection products, and the number of differentiated products faster and better by accelerating the development of new products and further acquisitions.