Managed Access Plans for orphan drugs can generate meaningful real-world data to support reimbursement and commercialization
By Becky Thompson, Director, Real-World Evidence Solutions, PAREXEL International
With rare diseases, the number of patients enrolled in randomized controlled trials (RCTs) is often small. Managed Access Programs (MAPs) that make orphan drugs available to patients prior to regulatory approval can add valuable real-world data (RWD) to the clinical dossier to support reimbursement. However, it is often small, emerging companies that develop drugs to treat rare or ultra-rare diseases and these firms may find it especially difficult to execute MAPs.
MAPs for rare disease drugs pose unique challenges because:
Very small patient populations are often difficult to locate, even if patient interest is high.
It can be expensive to design and execute a MAP for a small cohort of patients.
Small emerging companies may lack the resources or knowledge to respond in a fair and transparent manner to a barrage of compassionate use requests for which MAPs are designed.
Planning and logistics excellence are key
For a small company with an orphan drug, and limited resources, the number one priority is always achieving regulatory approval and commercial launch. Apart from the commercial imperative, this is the best way to benefit the largest number of patients.
But there is also a humanitarian need to get new drugs to patients who need them expeditiously. Indeed, developers can open themselves up to thorny ethical issues if they don’t have a MAP in place. For example, one CEO of a small company that developed an ultra-rare disease drug recently faced a dilemma when the company finished its Phase II trial with no inventory of its drug left over. A patient who had participated in the double-blind trial was convinced he had been on the study’s active arm and was improving. Once the trial stopped, his condition began to worsen, and he called the CEO every day begging for access to the drug.
Smaller companies can struggle to fulfill such requests especially if a drug is expensive to manufacture and its randomized controlled trial (RCTs) takes top priority.
But driven by the increasing participation of vocal and well-informed patient advocacy groups (PAGs), larger companies increasingly focus on designing and implementing fair and transparent MAPs.
For example, in 2015 Janssen launched a pilot partnership between Janssen and New York University’s Division of Medical Ethics to form the Compassionate Use Advisory Committee (CompAC). After a patient’s physician completed and submitted a request for access to J&J’s unapproved drug for multiple myeloma, daratumumab, requests were reviewed by Janssen for eligibility and then assessed and triaged by the CompAC (comprised of independent, external physicians, ethicists, and patient advocates) from a scientific perspective. CompAC’s recommendations were then considered by Janssen before it made a final decision on distributing daratumumab for compassionate use. After 19 months of operation, 100% of the CompAC’s recommendations were accepted by Janssen and a total of 165 daratumumab requests were approved, leading J&J to expand the pilot program to additional investigative medicines in its portfolio.
How smaller companies can cope
Start thinking about the ability to support a MAP at the start of development
Companies with promising orphan drugs should expect preapproval compassionate use requests. MAPs should be an early planning topic.
2. Consider outsourcing for global distribution
If there is one patient per country in 20 different countries, it’s a huge logistical burden to meet the differing regulatory requirements for each locality, and then distribute an investigational product across the globe in a cost-effective manner. It will be difficult to know where requests will come from. The drug may need to get to, say, Switzerland within a week, which requires both regulatory and import/export knowledge, and logistical nimbleness.
3. Make sure early access programs are science-based and transparent
No company wants to create negative publicity with a MAP that is not fair and transparent. Emulating some of the best practices demonstrated in J&J’s CompAC initiative—such as external expert review, clear eligibility criteria, and science-based decision making—is crucial.
Using MAPs to collect RWD is a particularly valuable way to generate quality data about an orphan drug’s risks and benefits and small companies that plan ahead will benefit, as will the affected patient populations.
 www.janssen.com. (2018). What is CompAC?. [online] Available at: https://www.janssen.com/compassionate-use-pre-approval-access/compassionate-use-advisory-committee [Accessed 26 Nov. 2018].
 Caplan, A., Bateman-House, A., Waldstreicher, J., Fedor, L., Sonty, R., Roccia, T., Ukropec, J. and Jansson, R. (2018). A Pilot Experiment in Responding to Individual Patient Requests for Compassionate Use of an Unapproved Drug. Therapeutic Innovation & Regulatory Science, p.216847901875965.