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Need for speed

Accelerating access to drugs for orphan diseases benefits patients and industry

An illustration of a fast carThere are significant challenges to successfully developing and commercialising an orphan drug. What approaches are pharmaceutical companies using to get a new product through development and approval? What do you do when your drug for an orphan disease has secured central European Medicines Agency (EMA) approval, but it will be months before the drug is available in all EU countries? Such delays could be too long for critically ill patients with limited treatment options.

As the number of effective drugs available in the key therapy areas increases and more generic products become available, pharmaceutical companies are looking to develop orphan drugs both to meet the unmet needs of patients and to achieve a commercial return on their investment.  

With greater focus on areas of unmet patient need, the advantage of 10-year market exclusivity, the opportunity for a company to demonstrate the value of its drug to physicians and health economists from its first use in patients and the potential commercial returns from orphan drugs, this market is increasingly attractive to both pharmaceutical and smaller biotech companies.

However, ensuring an orphan drug reaches the market is a big challenge. There is a significant failure rate during drug development and clinical trials. Data published by P F Dimond in 'Big pharma adopting orphan drug strategy', published in Genetic Engineering and Biotechnology News (December 14, 2009) revealed that, of 1,994 orphan drug designations granted, only 339 actually reached the market.

In research and development, large pharmaceutical companies are increasingly buying in molecules from smaller biotech companies to benefit from their expertise and focus in developing such niche products; in other cases, they are collaborating to bring these molecules from the laboratory and into clinical trials. In turn, smaller biotechs are looking to large pharma for their experience in running clinical trials and their commercial expertise in then getting a product to market. At a time when key stakeholders are increasingly focusing on unmet needs, orphan drugs and the potential benefits they offer both patients and payers, mean that these collaborative relationships will increase.

There is already evidence of a mind shift, with some global companies restructuring internally, adopting a vertical structure in individual therapy areas spanning the spectrum from R&D to commercialisation. In others, orphan drugs are assigned to one dedicated division within a company from which collaborations are undertaken with other research partners and discrete specialised areas, such as diagnostics. 

While collaborations give both sides the best chance of bringing orphan drugs to market, the importance of appropriate clinical data must not be underestimated. Often, smaller biotech companies do not have the experience or the resource to construct and deliver robust clinical trials from a broad patient population, so it is a natural step for them to work with large pharma to achieve this. With a high failure rate and the industry battling for a place in the orphan drug market, clinical trial data that can demonstrate the efficacy and safety of a molecule as early as possible is one of the ultimate product development goals. Adaptive clinical trials that amalgamate phase II and phase III trials are being used increasingly to provide data that demonstrate efficacy and the meeting of clinical endpoints earlier.

Predictive biomarkers, that forecast the likelihood of response to a particular molecule, are now being used. Developing a drug in this way alongside the use of related diagnostics can help with patient selection and treatment decisions, essentially using molecular diagnosis of disease to prescribe the right treatment to the right patient. During drug development and clinical trials, biomarkers can determine drug efficacy better with fewer patients as well as providing early information about unpromising compounds. This targeted and highly selective approach enables companies to abandon their efforts earlier where necessary and reallocate time and resources to other compounds. 

As with all drug development, orphan drugs face the hurdle of getting the molecule into later phase trials with patients, from which data can demonstrate that clinical endpoints have been achieved. When this happens, it is a major breakthrough for patients with unmet needs. The fact that they have access to a clinical trial means they have access to a medicine where they had no other treatment option previously. However, the inclusion and exclusion criteria for clinical trials are so stringent that many patients who may benefit from access to a particular orphan drug are not accepted on to a trial. For some patients with unmet needs, this could potentially mean the difference between life and death and, understandably, patients and their physicians are seeking ways to ensure they are not excluded from access to new treatments.

New options
For patients who are terminally or seriously ill, have exhausted all available therapies and cannot enter a clinical trial, access to an investigational drug or biologic outside the trial setting or prior to launch can represent a new treatment option. In addition, physicians are more aware than ever of the therapy options available to patients with unmet clinical needs, their knowledge sharpened through international medical conferences, web-based information services and social media.

Demand for access can come from a variety of places, but usually physicians are on the front line for receiving access requests from patients, who also have access to a wealth of information through the internet, patient organisations and government sites.

Recognising this situation, governments have established regulations that allow patients with unmet medical needs to gain access to drugs prior to their approval for general marketing. Through global access management solutions, pharmaceutical and biotechnology companies can provide access to drugs in their pipeline to patients with serious or life-threatening conditions including cancer and infectious diseases, as well as rare diseases.

Global access management strategies can be delivered through Expanded Access Programmes (EAPs) in the US and Named Patient Programmes (NPPs) in the rest of the world (also known as early access programmes; named patient supply and compassionate use programmes). 

NPPs are a means of meeting patients' unmet medical needs. They are controlled and restricted access programmes set up by pharmaceutical and biotechnology companies under which physicians and pharmacists can gain access to investigational therapies on a 'named' patient basis.

NPPs provide access to medicines that:

• Are still in clinical development and have yet to be approved
May never be approved, but still have medicinal value for a very small population (for example, some orphan drugs)
Are approved in one country, but not in another
Have been discontinued or withdrawn in a particular market
Are an alternative to a drug discontinued globally.

When considering global access management solutions, companies must make certain that there is adequate supply of the drug to complete registration studies and support the access programme in parallel. Another consideration is the resource needed to establish and run the programme, including processes for handling and vetting requests, the mechanisms to review physicians requesting the drug and procedures to handle adverse event reporting. Another key factor is proper vetting of physicians and pharmacists.

Considering the limited patient numbers, putting a NPP in place for an orphan drug can be effective in providing access to a small patient population that may be distributed across the world. Seeking approval in dozens of countries may be impractical; access management solutions would help companies reach such populations effectively.

Case study: Ceplene for Acute Myeloid Leukaemia
The poor prospects for long-term survival in acute myeloid leukaemia (AML) strongly motivated EpiCept to provide patients with its drug Ceplene in advance of the commercial introduction. Ceplene is the first approved immunotherapy for remission maintenance and prevention of relapse in adult AML patients in first remission. AML is an orphan disease, with about 16,000 to 18,000 new patients diagnosed each year worldwide.

EpiCept made Ceplene available on a named patient basis in Europe and in dozens of other geographies, including Latin America, Asia/Pacific, Australia, Israel and Canada. 

It has been approved in the EU, but regulatory constraints and decentralised reimbursement processes delayed actual launches in individual countries for more than a year. 

As a result of this, and the fact that there is no other therapy that can prevent relapse in AML patients, EpiCept saw the need to make the drug available to patients prior to commercial launch.

Establishing the programme required about 10 weeks. Its initiation in the EU was timed to coincide with the date the drug was ready from a manufacturing standpoint and had complete and final EMA approval and sign-off.

In order to navigate the regulatory and logistical pathways associated with NPPs and remain in compliance with all authorities, EpiCept partnered with specialist in this field, Idis. This allowed EpiCept's functional teams to stay focused on preparing for upcoming commercial launches and approvals.

Practical solution
For patients with life threatening rare diseases, licence approval or commercial launch of an innovative new drug may come too late. Access management solutions like NPPs offer a practical solution, as they enable well-regulated, well-controlled access to potential new treatment options. They can be used by companies of all sizes, from large to emerging, for significant patient populations and rare diseases, for patients in any location.

No matter what their structure, these programmes share an important goal: to help patients with unmet medical needs.

The Author
Simon Estcourt is a senior vice president and director at Idis

To comment on this article, email

12th October 2010


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