hot topic operational challenges for biosimilar studies

01 HOT TOPIC Operational Challenges in Biosimilar Studies

04 REGULATORYFRAMEWORK UPDATES

05 ARTICLES & REPORTS OF INTEREST

HOT TOPICOperational Challenges for Biosimilar Studies by Hazel GorhamDirector, Biosimilars Development, Scientific Affairs

A number of top-selling biological products in key therapeutic areas such as cancer, diabetes, and rheumatoid arthritis are due to lose patent protection over the next few years. IMS Health estimates

that US$67 billion in global sales will come off patent by 2019. This “patent cliff” together with public healthcare budget cuts, advances in technology for the manufacturing of biologics, and many countries now having developed legal and regulatory pathways for the approval of biosimilars, has fuelled the race for pharmaceutical companies to get their biosimilar products to market.

This article explores some of the unique operational challenges associated with the development of a biosimilar product, and how these issues can be addressed from the outset with strategic planning.

1 . Reference Product Like the manufacturers of an origina-tor reference product, biosimilar man-ufacturers must demonstrate a prod-uct’s quality, efficacy, and safety. The difference between biosimilars and an originator product is that approval is based on a demonstration of similarity to the previously approved originator reference product1 (Figure 1).

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B I O S I M I L A R S N E W S L E T T E RVolume 5 , January 2015

Welcome

Welcome to the fifth edition of Biosimilars Newsletter, a quarterly publication dedicat-ed to keeping you updated on current biosimilars news, including the global regulatory landscape, biosimilars articles and reports, and company news as reported in the com-pany press releases.

This edition's "hot topic" explores some of the unique operational challenges as-sociated with the development of a biosimilar product and how these issues can be addressed from the outset in strategic planning.

INSIDE THIS ISSUE:

01. Biosimilars NewsletterWelcomeHot Topic

04. Regulatory Framework UpdateEuropeUnited States Rest of World

04. Approved & Under ReviewEuropeUnited StatesRest of World

04. Regulatory Meetings

05. Articles & Reports of Interest

06. Company News

07. Company News

Next Edition

PHASE IV

PHASE II I

PHASE I

PRE-CLINICAL

EXTENSIVE MOLECULARCHARACTERIZATION PROGRAM

Post-marketing surveillance and ongoing safety monitoringplanned post approval

Demonstrate efficacy with comparable safety profile in patients – the most sensitive modelCompare immunogenicity

Comparable pharmacokinetics and pharmacodynamics

In vivo and in vitro assays confirm biosimilarity in terms of pharmacodynamics and toxicity

Comparability demonstrated with regards to proteinstructure and product quality

Figure 1. The stepwise approach to demonstration of biosimilarity between a biosimilar and the originator reference product

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BIOSIMILARS NEWSLETTER | Volume 5, January 2015

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Figure 2. An Example of Batch to Batch Varability of Biological Activity of a Biologic Drug Substance

Schneider, C.K.: Biosimilarity: A better definition of terms and concepts. 25th Annual DIA EuroMeeting, 04-06/03/2013, Amsterdam

Figure 3. Comparison of the Different Pre- and Post-change Batches of Rituxan/Mabthera

Comparability with the reference product starts at the beginning of the devel-opment of a biosimilar product when the “goal posts” are established for its development. The EMA guideline EMA/CHMP/BWP/247713/2012 (revision 1)2, refers to this as determining the Quality Target Product Profile or QTPP. The development of the QTPP and the direct comparative analysis of the biosimilar product under development to the reference product requires the procurement of multiple batches of reference product with differing expiry dates. The reason for the analyses of multiple batches of reference product is to determine the inherent variability of the reference product’s critical quality attributes* (CQA) (Figure 2), including changes due to modifications of man-ufacturing processes 3,4 (Figure 3). The range of each attribute needs to be de-termined when setting the “goal posts” for the development of the biosimilar product. The procurement of multiple batches of reference product with differing ex-piry dates is often problematic. Originator companies only release a limited number of batches of commercial stock with different expiry dates over a giv-en period of time. In view of the observations from Figures 2 and 3, companies pursuing biosimilars development will therefore need to strategically plan ahead to acquire multiple batches of reference product over a significant time period, prior to the start of development and manufacturing activities. Having established a detailed comparative analysis of physiochemical and biological activity of the biosimilar against the reference medicinal product, comparative non-clinical (in vitro and in vivo studies) and clinical studies need to be undertaken. Comparative Phase I pharmacokinetic/pharmacodynamic (PK/PD) studies, designed to demonstrate a similar PK profile of the biosimilar to the refer-ence product with regards to key PK parameters is an essential part of the biosimilar development program. Biosimilar bioequivalence studies are gen-erally large in size and can involve up to hundreds of subjects depending on the molecule. Obtaining large quantities of a single batch of reference product can prove to be extremely challenging. Some variability, be it the biosimilar or reference product, is expected between differing batches of product. Such variability can be detrimental to the outcome of a Phase I PK/PD study; there-fore; it is preferable to use a single batch for the dosing of the subjects and the development/validation of required biological assays. A Phase III comparative efficacy study, designed to determine if the investi-gational therapy is similar to that of reference product with regards to efficacy and safety, requires the procurement of even larger quantities of the reference product. Though the use of multiple batches of reference product is acceptable and preferable within the Phase III setting, ensuring the continued supply of reference product is challenging as the originator companies carefully control the release of commercial supplies. Furthermore, the total cost for purchasing the reference product should also be taken into account, as it can form a sig-nificant part of the overall study budget. In addition to the challenges associated with the procurement of reference product, the release of investigational medical product (IMP) by a Qualified Person and importation of the IMP into many countries within Europe re-quires a Certificate of Analysis (CoA). Obtaining a CoA for commercial sup-plies of reference product can prove difficult. In fact, supportive documenta-tion for reference product purchased from the United States will not include a CoA. If a CoA is not available, the biosimilar developer will need to undertake its own analysis of the reference product to be able to produce a CoA, which could have significant impact on timelines.

* A critical quality attributes (CQA) is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribu-tion to ensure the desired product quality.

2. Blinding of Investigational Medicinal Product (IMP)

Regulators require that every effort should be made to conduct double-blind biosimilar efficacy studies. If the studies cannot be double-blind, then justifi-cation must be provided2. "Usually, it is necessary to demonstrate comparable clinical efficacy of the bio-similar and the reference medicinal product in adequately powered, random-ized, parallel group comparative clinical trial(s), preferably double-blind."

Ideally, the best way to blind a biosimilar study is to have an exact copy of the container, stoppers, seals, etc, as those of the reference product. This is usually extremely challenging for various reasons including the complexity of the drug container such as drug pens and patent protection issues. If an exact matching container is not possible, then consider transferring drug from an existing container to another, and then package and label. Stability data in the new containers for both the reference and biosimilar products will be required. Planning for blinding of the IMP should be instigated early within the product development program (ie, during CMC development). Leaving this activity to the start of the clinical development program can result in significant, pre-ventable delays.

If blinding of the study medication is not possible, then blinded and unblind-ed investigator site staff and study teams need to be set up to ensure the in-tegrity of the data. Processes also need to be put in place to ensure a “firewall” between the unblinded and blinded teams.

Schiestl, M., et al.: Acceptable Changes in Quality Attributes of Glycosylated Biopharmaceuticals. Nature Biotechnology, 29: 310-312, 2011

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[email protected]

3. Background Treatment

Depending on the nature of the biosimilar product under investigation, back-ground treatment may need to be supplied to/costs reimbursed to the sites during the course of the study (eg, cytotoxic drugs in filgrastim biosimilars stud-ies.) One approach is for the hospital/institution pharmacy to buy in supplies of the required chemotherapy drug(s) and for the sponsor to reimburse the costs. However, there are a number of issues with regard to this approach, such as:

• A large number of hospitals/institutions will no longer accept such an agreement due to the administrative and financial burden

• When pharmacies source drug supplies from local suppliers, the brand purchased will be outside the sponsor's which, in turn, could potentially affect the quality of the study data. An alternative strate-gy is to centrally supply chemotherapy drugs to all the sites, thereby ensuring the quality of the drugs provided. This approach will require the procurement of large quantities of drugs, repackaging, and label-ing, and importation and distribution of drug supplies to the sites via regional or a global drug distribution center(s), all of which will need to be carefully monitored to ensure continuity of the supply chain. Furthermore, shelf life should be taken into consideration to mini-mize re-labeling activities and drug wastage.

4. Patient Recruitment

Patient recruitment is the most challenging aspect of the clinical trial process, consuming approximately 30% of the clinical timeline and often leading to trial delays. In addition to the standard clinical trial recruitment demands, biosimilar trials face a new set of challenges, namely the following:

• An awareness of what a biosimilar medicinal product is• Competition against new biological molecules for the same indication• Potential problems arising from changes in the standard of care• Protocol adherence• Lack of incentives for both investigators and patients

4.1 An Awareness of What a Biosimilar Medicinal Product IsTrial site staff/physicians and patient education are critical to the recruitment of patients to biosimilar trials. An ISR report 5 detailing improving patient re-cruitment into biosimilar trials has been presented and addresses a number of recommendations on how to interact and communicate with patients. It also provides strategies on how sites can enhance patient recruitment. Amongst the various recommendations is the importance of investing in both the ed-ucation of the investigators and in their patients so they can understand the potential value of biosimilars, including providing affordable alternatives to innovator specialty medications, thereby increasing patient access to treat-ments that would otherwise be beyond their financial means.

4.2 Competition Against New Biological Molecules for the Same IndicationCompetition for patient populations is fierce. For example, according to clinicaltrial.gov (07 Jan 2015), there are currently 55 actively recruiting Phase III studies for adult rheumatoid arthritis patients of which 2 are for biosimilar products. Although not all of the reported remaining 53 studies will involve new biological molecules, these numbers give an idea of the competition for patients within a single indication. 4.3 Potential Problems Arising from Changes in the Standard of CareTreatment for patients is continually evolving, and over time new treatment therapies/regimens are accepted as the standard of care. Furthermore, differ-ent regimens are used in different countries. For example, several regimens are approved by American Society of Clinical Oncology (ASCO) for breast

cancer treatment. This can prove to be problematic when undertaking an equivalence efficacy study between the biosimilar and reference product. If such concerns exist, then a feasibility study in the countries of interest should be undertaken as soon as possible, to confirm current practices and the accep-tance of the proposed study design.

4.4 Protocol Adherence Differing local practices for treatment by the reference product and/or back-ground treatment can prove to be problematic. Assumptions made by investi-gational site staff based on local practice can lead to protocol deviations. Site support with regard to protocol training and supportive protocol study aids are key in obtaining quality data.

4.5 Lack of Incentives for Both Investigators and PatientsThere can be a lack of incentive for investigators to participate in biosimilar clinical trials compared to studies involving new biological molecules due to a perceived lack of novel study design and scientific interest. Patients may not see any advantage to participating in a biosimilar study. The key to overcoming this issue is the education of the site staff/physicians and patients about the potential value of biosimilars. Patient recruitment can be accelerated by choosing the countries/markets with the greatest unmet need for biosimilars. Although the quality of research can be very high in these countries, experience in the use of the reference product may be limited; therefore, site support is critical.

Conclusion

Biosimilar development programs face a number of unique operational chal-lenges associated with the guiding principle of establishing similarity between the biosimilar and the reference product. As the ”patent cliff” approaches, the race to launch biosimilars products to market will intensify as companies compete to be amongst the first to establish their position within a rapidly evolving marketplace. Careful strategic planning and understanding the op-erational challenges are crucial in minimizing the impact of key issues as-sociated with the development of a biosimilar product and maximizing its commercial potential.

References

1Guideline on similar biological medicinal products, CHMP/437/04 Rev 1, 23 October 2014

2Guideline on similar biological medicinal products containing biotechnol-ogy-derived proteins as active substance: quality issues (revision 1), EMA/CHMP/BWP/247713/2012, 22 May 2014

3Schneider C.K. Biosimilars in rheumatology: the wind of change. Ann Rheum Dis March 2013 Vol 272, No 3 : 315-17

4Schiestl M, Stangler T, Torella C, et al. Acceptable changes in quality attri-butes of glycosylated biopharmaceuticals. Nat Biotechnol 2011;29:310–12

5Industry Standard Research (ISR) Report. Improving Patient Recruitment in Biosimilar Trials September 2012

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Europe EMA Publishes Revised Guideline for Biosimilars

The European Medicines Association (EMA) has finalized and published its long-awaited revised guidelines on biosimilars. The most significant

change within the new guidance is the possibility for developers to use a com-parator authorized outside the European Economic Area (EEA) during the clinical investigation of a biosimilar. This new concept is expected to facili-tate the global development of biosimilars and avoid unnecessary repetition of clinical trials. The revised guideline will come into force as of 30 Apr 2015; however, ap-plicants can apply some or all provisions of this guideline from 29 Oct 2014.Link to EMA: http://www.fda.gov/downloads/Drugs/GuidanceCompli-anceRegulatoryInformation/Guidances/UCM417290.pdf

United StatesFDA Announces List of Guidance Documents for 2015

The Food and Drug Administration (FDA) published a list of guidance documents that will be released during 2015. The 4 documents pertain-

ing to biosimilars are:

• Biosimilars: Additional Questions and Answers Regarding Implemen-tation of the Biologics Price Competition and Innovation Act of 2009

• Considerations in Demonstrating Interchangeability to a Reference Product

• Labeling for Biosimilar Biological Products • Statistical Approaches to Evaluation of Analytical Similarity Data to

Support a Demonstration of Biosimilarity

It is interesting to note that the FDA currently appears to have no immediateplans to issue draft guidance on the naming of biosimilars, a point of conten-tion in the United States and elsewhere.Link to FDA guidance document: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM417290.pdf

Rest of WorldChina Issues Draft Biosimilars Guideline

T he China Food and Drug Administration has issued draft guidance "Guidelines for R&D and Evaluation Techniques of Biosimilars" that

lays down principles for developing biosimilars of biologics already ap-proved in China, including products intended to be extrapolated to mul-tiple indications.

Under the "step-by-step" approach, the agency explains that "subsequent comparability tests may be exempted" once a biosimilar developer can demonstrate "no or little difference" compared to the reference product.

The draft stipulates that biosimilars should have the same amino acid sequences as the reference products, which must already be registered in China. It also notes that special attention must be paid to complex biolog-

Regulatory Framework Updates

ics, such as antibodies and antibody-drug conjugates (ADCs). The document also lists requirements for randomized, double-blinded comparator clinical studies, accessing comparator compounds, establish-ing stability, and identifying immunogenicity. Applicants are also instruct-ed to include pharmacovigilance and risk management plans.

The draft states that the extrapolation of use of a biosimilar from an initial indication to others should be "individually considered" based on indica-tion, target, and dosing.

The document does not mention substitutability or generic naming, nor does it address whether China will establish a separate pathway for biosimilars. Link to unofficial translated translation of draft guideline: http://www.biocentury.com/elearning/Whitepapers/formChinaBiosimi-lars#.VMLlcnDF-md


The FDA's Oncologic Drugs Advisory Committee met on 07 Jan 2015 to dis-cuss the agency's first-ever biosimilars application. Sandoz, a division of

Novartis, filed a biologics license application (BLA) in July for EP2006, a biosim-ilar version of Amgen's top-selling Neupogen (filgrastim).

In documents released by the FDA advisory panel ahead of meeting, agen-cy staff recommended clearance of Novartis' biosimilar version of Amgen's Neupogen (filgrastim). Reviewers said that there were "no clinically meaningful differences" between the 2 drugs, backing approval of Novartis' biosimilar in all 5 indications for which Neuprogen is approved.Link to FDA advisory meeting material: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/oncologicdrugs-advisorycommittee/ucm428782.pdf.

Europe/ Rest of World None reported

Biosimilars Applications Approved & Under ReviewUS / Rest of World

Regulatory MeetingsUS

For the latest FDA report on the number of biosimilar biological product devel-opment* (BPD) Type 1-4 meeting requests received and/or meetings held, follow the link below. As of September, the FDA has received 42 biosimilars meeting requests and held a total of 33 meetings. Link to FDA site:http://www.accessdata.fda.gov/FDATrack/track?program=cder&id=C-DER-RRDS-Number-of-BPD-meetings

Europe/ Rest of WorldNone reported

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maceutical Statistics, 24: 1154–1164, 2014.

A number of top-selling biologic brands in key therapeutic areas

such as cancer, diabetes, and rheu-matoid arthritis are due to lose prod-uct patent protection over the next few years, opening a wealth of oppor-tunities for biosimilar players. IMS Health estimates that US$67 billion in global sales will be off patent by 2019. Keen to be part of the biosimi-lar world, many countries throughout the world have established legal and regulatory pathways that allow devel-opment of biosimilar products for the global market.

This article explores the global regu-latory framework, past and present, and scientific and statistical consid-erations for the development of bio-similars.

Click here to read/locate the article www.ncbi.nlm.nih.gov/

Research & Generic/Biosimilar Industries Call for Integrated Life Sciences Strategy for Europe

European research and generic/biosimilar industry associations

have called for an integrated life sci-ence strategy for Europe ahead of the adoption of the European Commis-sion Work Program.

The European Federation of Pharma-ceutical Industries and Associations (EFPIA) and the European Generic medicines Association (EGA) reiter-ated their joint Europe 2020 strategy submission to welcome Commission President Juncker Commission’s work program for an industrial policy for the globalization era.

The joint submission asserts that the EU pharma sector can compete glob-ally if the EU:

• adopts efficient regulatory mea-

ISR Report European Physicians’ Biosimilar Views: A Primer

In July of 2014, Sandoz announced that it had filed the first ever bio-

similar application in the US with the Food and Drug Administration (FDA) via its 351(k) pathway.

Earlier in 2014, a landmark approval occurred in Europe, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opin-ion recommending approval for In-flectra, a biosimilar medicine to the reference medicinal product, Remi-cade, the first monoclonal antibody to be approved through the European Medicines Agency (EMA) biosimilars regulatory pathway.

So the biosimilar approvals are com-ing, but will physicians prescribe them? To find out, ISR asked 348 board-certified physicians across Spain, Italy, France, and Germany what they thought about prescribing biosimilar products. Topics examined within this article include:

• European physicians’ familiarity with biologic and biosimilar med-icines

• Physician attitudes toward clini-cal development requirements for biosimilar medicines

• Physician views on pharma-cy-level substitutions

• Importance of medication cost when prescribing

• Impact biosimilar pricing has on prescribing recommendations

• Physician concern with safety and efficacy of biosimilar products

• Current and future prescribing behavior for biosimilar medicines

Click here to read/locate the article www.isrreports.com

Biosimilars: Where We Were and Where We Are

Rodeina Challand, Hazel Gorham, and John Con-stant; Journal of Biophar-

Articles & Reports of Interest

sures through open and transpar-ent input from health care stake-holders;

• promotes stable and predictable pharmaceutical markets that sup-port investment in innovation and that stimulate healthy and sustain-able generic and biosimilar medi-cines competition;

• makes Europe an attractive loca-tion for investment in research, development, and manufacturing of pharmaceuticals; and

• cooperates with the industry to ad-dress new health risks and expand its manufacturing capabilities to securely provide for its own med-icine needs.

Click here to read/locate the article www.efpia.eu

Biotechnology Industry Organization Urges FDA to Release Guidance on Biosimilars

B iotechnology Industry Organiza-tion (BIO) has called on the FDA

to release final guidance on processes and scientific criteria for the approv-al of biosimilars, outline its approach to naming and labeling, and clarify its conditions for determining a bio-similar to be interchangeable with its reference biological.

Click here to read/locate the article www.bio.org

Q&A: Rodeina Challand, Executive Director Biosimilar Development on the Naming of Biosimilars - the INN Debate

W ith the publication of the WHO draft proposal for the

naming of biologics, what is the po-tential impact on the business of bi-osimilars?

In this Q&A article, Rodeina Challand gives the background to the naming system and how the system works

for biosimilars. She then discusses the regulatory agencies' positions, whether the proposed WHO naming scheme would, if adopted, result in global harmonization, and, finally, what this means to biosimilars busi-nesses.

Click here to read/locate the article contractresearch.pharmaceuti-cal-business-review.com/

Regulatory & Clinical Con-siderations for Biosimilar Oncology Drugs

Charles L Bennett et. al. The Lancet Oncology Vol-ume 15, No. 13, e594–e605, December 2014.

B iological oncology products are integral to cancer treatment, but

their high costs pose challenges to patients, families, providers, and in-surers. The first wave of oncology bi-osimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, as well as in Australia, Ja-pan, China, Russia, India, and South Korea. Their use is emerging world-wide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approv-al exist. This review article discusses oncology biosimilars and summarizes their regulatory frameworks, clinical experiences, and safety concerns.

Click here to read/locate the article www.thelancet.com


Amgen Files a Lawsuit & a Citizen’s Petition Against Sandoz

Amgen has filed a lawsuit and a citizen’s petition against San-

doz, which is seeking regulatory ap-proval in the United States to market a biosimilar version of Amgen’s med-ication called Neupogen.

The issue is an interpretation of US law – the Biologics Price Competition and Innovation Act – that governs the pro-cedures a company must follow when seeking to win regulatory approval of a biosimilar medicine. In this instance, Amgen charges that Sandoz is not fol-lowing the rules. The outcome may have wider implications for the phar-maceutical industry as biosimilars be-come available in the US.www.regulations.gov

STADA & mAbxience Enter into Negotiations Over Adalimumab Biosimilar

S tada and mAbxience have agreed to negotiate the in-licensing of

an adalimumab (Humira®) biosimi-lar. The letter of intent stipulates that the 2 negotiating parties will come to a decision within the next 6 months. The original product, Humira®, is the world's top-selling biopharmaceutical with a sales volume in 2013 of approx-imately US$10.66 billion.

mAbxience is a biotech company spe-cializing in research, development, and manufacturing of biosimilars. It has 5 products in development and will have a global presence in over 50 countries. mAbxience plans to develop and manufacture the biosimilar adali-mumab at the Genhelix biopharma-ceutical plant located in Leon, Spain.Company Press Release 18 Nov 2014www.stada.com

Momenta Pharmaceuticals Announces Acceptance of a Clinical Trial Application

LG Life Sciences Signed the Contract with Mochida for Humira® Biosimilar

S outh Korea-based LG Life Sci-ences and Japan-based Mo-

chida Pharmaceutical (Mochida) announced that they had signed a deal in which Mochida will have exclusive right for the development and sale of the Humira biosimilar in Japan. After commercialization, LG Life Sciences will supply the drug product to Mochida.

LG Life Sciences is currently carry-ing out a Phase I clinical study of its biosimilar (LBAL) in South Korea, according to ClinicalTrials.gov. The trial is being carried out to study the pharmacokinetics, safety, and tolera-bility of LBAL compared to the orig-inator biological, AbbVie’s Humira (adalimumab) and is expected to be completed in March 2015.Company Press Release 15 Oct 2014www.lgls.com

EPIRUS & Livzon Mabpharm Enter Collab-oration Agreement for China

Epirus has announced the signing of a royalty-bearing, multi-prod-

uct collaboration agreement with Livzon Mabpharm, a Chinese bio-technology company focused on the development, manufacturing, and sale of antibody-based drugs.

Under the terms of the agreement, Epirus and Livzon will work together to develop, manufacture, and com-mercialize up to 5 biosimilar prod-ucts. The first collaborative product is Epirus’ Remicade biosimilar BOW015 (infliximab), which was recently ap-proved in India. Livzon will conduct any additional development work necessary for the approval of BOW015 in China and Taiwan. Livzon will also serve as the preferred supplier of BOW015 in these territories. Company Press Release 25 Sep 2014ir.epirusbiopharma.com

in Europe for M923, a Biosimilar Version of Humira®

M omenta Pharmaceuticals an-nounced the acceptance by the

UK Medicines and Healthcare Prod-ucts Regulatory Agency (MHRA) of a Clinical Trial Application (CTA) to initiate a clinical trial for M923, a bi-osimilar version of Humira® (adalim-umab), in its collaboration with Bax-ter International's biopharmaceutical business. Company Press Release 01 Dec 2014ir.momentapharma.com

Ranbaxy Launches India’s First Biosimilar of Infliximab Drug, Infimab

R anbaxy has announced the launch of InfimabTM (BOW015),

the first Remicade® (infliximab) bio-similar in India.

InfimabTM is being introduced in the Indian market through a licens-ing partnership with Epirus Biophar-maceuticals, focused on the global development and commercialization of biosimilar monoclonal antibodies. The innovator reference product is currently marketed for the treatment of inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis, ulcerative coli-tis, psoriatic arthritis, and psoriasis.Company press release 01 Dec 2014www.ranbaxy.com

Zydus Launches Biosimi-lar Adalimumab in India

Zydus Cadila has announced it has launched its biosimilar of

adalimumab in India. The biosimi-lar version of Abbvie’s Humira® has been approved by the Drug Controller General of India and will be marketed under the brand name, Exemptia to treat autoimmune disorders, includ-ing rheumatoid arthritis, juvenile id-iopathic arthritis, psoriatic arthritis, and ankylosing spondylitis.

Zydus claims that Exemptia is the first biosimilar of Humira® to be launched by any company in the world and is a “fingerprint match” with the orig-inator in terms of safety, purity, and potency of the product. According to Zydus, Exemptia is produced through a non-infringing process and is a novel non-infringing formulation.

The biosimilar of adalimumab is a part of Zydus’ robust biologics pro-gram of 24 biologics, including bio-similars and 3 novel biologics. Company Press Release 09 Dec 2014www.zyduscadila.com

Mylan Commences Phase III Clinical Trials for Its Insulin Analog to Lantus®

INSTRIDE 1 and INSTRIDE 2 are open-label, randomized, multi-

center, parallel-group clinical trials comparing the efficacy and safety of Mylan's insulin Glargine with that of Lantus® in Type 1 and Type 2 dia-betes mellitus patients, respectively. The purpose of both studies is to test whether Mylan's insulin Glargine once daily is non-inferior to Lantus® once daily when administered in combina-tion with other anti-diabetic drugs.Company Press Release 09 Dec 2014www.mylan.com

STADA In-Licenses Teriparatide

S tada has in-licensed teriparatide, thereby expanding the company’s

biosimilar portfolio. The teriparati-de biosimilar is being developed by Richter-Helm and is to be launched under the Stada label throughout Eu-rope following the patent expiration of the original product, Forsteo.

Under the terms of the agreement, in addition to a payment at the signing of the contract, Stada is obliged to make further payments depending on the progress of the project. Stada expects to launch teriparatide on the market in 2019 and will report the

Company News(The information provided is sourced directly from company websites.)

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Company NewsContinued

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resulting sales and make license pay-

ments to Richter-Helm.Company Press Release 13 Oct 2014www.stada.com

CKD Pharmaceuticals of CKD-11101 Achieves Comparable PK, PD, & Tol-erability Profile to that of NESP® (darbepoetin alfa)

In its Phase I pharmacokinetics study of CKD-11101 and NESP® after SC and IV administration in health male vol-unteers, CKD-11101 has shown a com-parable PK, PD, and tolerability profile to that of Kyowa Hakko Kirin’s Nesp® NESP® (darbepoetin alfa). CKD Pharm is planning to start a Phase III clinical study at the end of 2014 and expects to submit NDA for South Korea approval in 2018.Article Dated 18 Nov 2014www.pipelinereview.com

Next EditionLook out for the next edition of the Biosimilars Newsletter due out in April 2015.

Contact Rodeina Challand, Executive Director, Biosimilars Development, Scientific Affairs [email protected]

Hazel Gorham, Director, Biosimilars Develop-ment, Scientific Affairs

[email protected]

PRA Health Sciences4130 ParkLake Avenue, Suite 400 Raleigh, NC 27612 U.S.A.

Phone: +1 (919) 786-8200 Email: [email protected]