Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Portfolio strategies of cytotoxic drugs – current topics of regulatory economy ***

Claudia Keupp (Abschlußjahr: 2009)

Language English

The diagnosis "cancer" concerns many people: in Europe the mortality is about one million people per year or, in other words, in the Western industrial society every fourth death is caused by cancer.

The treatment of cancer includes surgery, radiation and chemotherapy leading to a healing rate of about 40 50 % of all malignancies worldwide. The medication used in anticancer therapy mainly may be divided into the "classic" cytotoxic drugs including for example the alkylating agents, vinca-alkaloids, taxanes and topoisomerase inhibitors and the target drugs where the medicinal products interfere with specific targets involved in carcinogenesis and tumour growth. Signal-transduction inhibitors, monoclonal antibodies and angiogenese inhibitors may be cited as examples for this group. Furthermore other treatment options like biological therapy, photodynamic therapy or laser therapy exist to fight cancer.

Thus it is not surprising that the oncological market may be called a market with a high growth potential in 2007 nearly 50 % of all new active pharmaceutical ingredients in the clinical development were against tumours and for the coming years growth rates of more than 20 % have been predicted.

A company which is operating in the field of oncological drugs has to actualise its portfolio to asset its position among its competitors. Different regulatory aspects however have to be taken into consideration within the management of the portfolio.

Taking the example of a fictitious company the strategic management process illustrates the different portfolio strategies in case of cytotoxic drugs and their correlation to regulatory affairs. The discussion of situation analysis and market needs, self-evaluation of the manufacturer and competitor analysis leads to the conclusion that cost minimisation, product differentiation and market focus respectively market expansion are suitable tools to adjust the portfolio to the economic situation.

The close connection between the marketing & sales department and regulatory affairs is illustrated by discussing the regulatory influence on the portfolio strategies be it the addition of new drugs, the maintenance of existing products or the giving up of non-profitable products whereas the focus is set to the situation in Europe.

According to Reg. (EC) 726/2004 the centralised procedure is mandatory for new anticancer compounds to obtain a marketing authorisation. Yet within the centralised procedure the legislation offers several possibilities as there are accelerated assessment procedure, conditional approval or approval under exceptional circumstances. Additionally to one of these approval procedures the manufacturer of an oncological drug may apply for an authorisation of his medicinal product as orphan drug if the relevant criteria are fulfilled. Finally compassionate use of drugs which are not yet authorised is one treatment option if no satisfactory alternative therapy exists.

With regard to the management of already authorised products especially variations have a high rank in oncology: anticancer treatment continually is evolving. By reason of this there always is the demand for improved pharmaceutical forms, further strengths or additional indications. New possible uses for approved drugs arise or new combinations are found to be effective thus leading to a high percentage of off-label use in the field of anticancer drugs. When a therapy seems to have a higher benefit for the cancer patients oncologists may of course adopt it and treat their patients accordingly though it is not yet approved. The companies however should have the (ethical) obligation to enlarge their authorisations as soon as the off-label use of their products at a respectable grade gets to their knowledge.

Finally the management of non-profitable existing products are discussed. The manufacturer constantly has to reassess his product portfolio to ensure alignment with its strategic focus possibly resulting in the decision to out-license certain products as they begin to lose market share. Reasons for this may be an increasing number of competitive products replacing established products from the market, obsolete therapeutic principles or formerly unknown adverse effects leading to degrading sales figures. Yet another reason for out-licensing may be that a product, though successful, does no longer fit to the companys actualised portfolio.

Considering the guidance documents for the development and authorisation of anti-cancer drugs it may be stated that, in contrast to other therapeutical fields where many guidelines exist, there is only few guidance concerning oncology. In the frame of this master thesis the main guidelines are discussed:

• "Guideline on Nonclinical Evaluation for Anticancer Pharmaceuticals" providing recommendations on the design and conduct of nonclinical studies for patients with late stage or advanced disease
• "Guideline on Strategies to Identify and Mitigate Risks for First-in-Man Human Clinical Trials with Investigational Medicinal Products", shortly "First-in-Man-Guideline", covering non-clinical issues for consideration prior to the first administration in humans and the design and conduct of trials in the initial phase of single and ascending doses during the clinical development
• "Guideline on the Evaluation of Anticancer Medicinal Products in Man" giving guidance on clinical drug development of anticancer medicinal products whereas the compounds are classified into cytotoxic and non-cytotoxic compounds.

Last a new Platinum-based cytotoxic drug of a fictitious company exemplifies the most promising regulatory strategy for the first marketing authorisation via a decision analysis. Due to the compounds efficacy in different tumour entities, common cancer types as well as rare indications, the company has to evaluate the most favourable strategy for positioning its new anticancer drug in the market. The “push marketing-strategy” with the first marketing authorisation in a main indication will establish the new cytotoxic drug in a market where it represents a possible alternative to efficient "state of the art"-therapies. The "pull marketing-strategy" on the other side with the first marketing authorisation in a niche indication will introduce the new compound as an innovative new standard offering new therapy options.

Considering the interests of marketing and regulatory affairs the decision analysis showed that the "pull marketing-strategy", to apply first for a marketing authorisation in a rare indication via conditional approval and additionally authorisation as orphan drug, bears the most advantages for the fictitious company. For the rare cancer type in question actually no gold standard exists and the company will be able to introduce its innovative medicinal product successfully as a new option.

In summary a close connection between the management board, marketing & sales department and regulatory affairs department facilitates the strategic decisions which lead to a companys success. It is important to develop successful portfolio strategies to stand its ground among the competitors, but it is not less important to consider the most suitable regulatory strategy to obtain efficient marketing authorisations.

Pages: 82, Annexes: 2, pages: 2