Tag Archives: FDA

Next Several Weeks of Critical Importance in U.S.

The next several weeks are a period of critical importance for the rare disease community in the U.S.  If Congress isn’t able to reach agreement on a budget deficit reduction plan by January, across-the-board funding cuts of 8.2% will go into effect for FDA, NIH and other federal agencies.  This would have devastating effects on the biomedical research enterprise. (more…)

Report from Washington. The 1st US Conference on Rare Diseases and Orphan Products.


The 1st US Conference on Rare Diseases and Orphan Products, co-organised by NORD (National Organization for Rare Disorders, USA) and the DIA (Drug Information Association), took place in Washington DC from 11 – 13 October 2011. Organised in partnership with the FDA, NIH and EURORDIS, this first conference was a huge success, assembling over 250 attendees who benefitted from discussions on drug development, de-risking investments, challenges in patients’ access, changes in the orphan landscape, the FDA and NIH processes, the US health care reform, changes in insurance reimbursement, off-label issues and compassionate allowance.

Separate tracks for patient advocates and organisations, researchers/drug and device companies, and investors were proposed. A stellar lineup of speakers, including NIH Director, Francis S. Collins, and Social Security Administration Commissioner, Michael J. Astrue, contributed to its impact and importance.

The second event in this new transatlantic series will be the 6th European Conference on Rare Diseases and Orphan Products (ECRD 2012 Brussels) taking place in Brussels, Belgium from 23 – 25 May 2012. Co-organised with the DIA Europe and NORD, this foremost conference on rare diseases will bring together all stakeholders in the European rare disease community at a crucial juncture.

The value of this trans-Atlantic series of conferences with patient-driven agenda partnering with regulators, policy makers, healthcare managers, industry, investors, academic leader is already tangible. Back from Washington, I see three strong points:

  • The converging calls by NORD and EURORDIS for an official policy of flexibility by drug regulatory and health technology agencies for rare diseases and orphan drugs. Francis Collins, NIH, highlight the huge current scientific potential to develop innovative approaches to treat or cure rare diseases. This analysis is shared by Ruxandra Draglia-Akli, Director for Health Research at the European Commission, who initiated the International Rare Disease Research Consortium with the ambitious goal of 200 new therapies for rare diseases by 2020. But the pathway is narrow and obstacles many between development between orphan designation and approval, called the Death Valley. A key leverage to activate is the way regulations are implemented on both side of the Atlantic. Experience shows that the European Medicines Agency (EMA) has a well established track record of flexibility with half of the 70 orphan drugs being approved based on conventional study design and also half being approved at the end of Phase 2. EMA has even adopted few years ago an Official Guideline on Alternative Study Design on Small Populations. An analysis prepared by NORD and FDA and first presented at the Washngton’s Conference on 25 years of experience  shows that out of 135 non-cancer orphan therapies approved for new chemical entities, 45 were “conventional studies”, 32 “administrative flexibility”, 58 “case by case flexibility”. NORD wants that FDA adopt an official policy of flexibility for orphan drugs as FDA did in the past for HIV and Cancer. EURORDIS is considering calling for similar offcial policy of flexibility for orphan drugs by the EMA ( providing opinions) and European Commission (DG SanCo providing decisions). Such official policy of flexibility by the main regulatory authorities for orphan drugs in the world would be particularly relevant and consistant with the objectives 200 new therapies by 2020 of the International Consortium strongly supported by the EU European Commission, US NIH as well as Canada, Japan and others. Although, if these two policies were to be parallel it will not be sufficient : hence my strong call on behalf of EURORDIS at the US Conference for a much closer and real collaboration between FDA and EMA. This transatlantic collaboration works effectively at the stage of the orphan designation, it is exemplary and good but not enough. Collaboration needs now to exist for protocal assistance so to agree on best and most realistic international study design so to generate faster better data for the risk & benefit assessment. We need a rolling-on joint protocol assistance dedicated to orphan drugs, both knowledgeable about the reality of rare diseases and flexible in its regulatory
  • The US Health Care Reform, the USA are confronted with the emergence of health technology assessment and its impact on orphan drugs. Considerations for the need to assess the effectiveness and comparative/relative effectiveness are growing ; In this regards, EU is much more advanced on this debate. The concepts are already clarified and approved as well as core methodology for the assessment. New approaches such as the scientifc assesssment of the Clinical Added Value of Orphan Drug, conditional pricing and reimbursement, and policy of pricing and reimbursement based on data generated are mature policies well on track for implementation. In the fielf of orphan drugs, these new policies are triggered by the dialogue between EURORDIS, industry, EU Member Sttaes autorities and European Commission. NORD has announced in the concluding panel of the Washington’ Conference that it will now look at these new approaches as policies transferable to the USA. Pivotal between the regulatory procedures and the health technology assessment : the marketing autorisation. Here too, new approaches are emerging, from industry and GSK in particular, calling for « Progressive Marketing Approval » one more bridge to link up between data generated for clinical trials and real life use. In all cases, post-marketing obligations or evidence generation plan to generate data on effectiveness, would gain from closer closer collaboration – here too – to generate post marketing evidence on risk, benefits and effectiveness fater with better quality data and increased statistical power. Both previous themes are connected to need to put in place international rare disease registries supporting pre-approval and post-approval research activities.
  • The potential for actual coordination on rare disease registries. In EU several projects are complementing each other to shape policy scenario based on best practices and public health needs (such as the EpiRare project) and to build EU-wide infrastructure for databases, biobanks and registries (recent FP7 Call). This is linked to the Working Group on Registries and Biobanks of the International Consortium which will define common international policies such as minimum data set, standard operating procedures, interoperability, etc. The NIH is supporting similar analysis, exchange of best practices, library of resources on registries. We are not yet there, but almost there. With goodwill on all sides, real resource saving and life saving convergences are at our door step.

Related links:
Updates from the conference (courtesy of NORD): http://rarediseases.org/patients-and-families/patient-meetings/dia-nord-oct-2011
Images from the conference (courtesy of NORD): http://rarediseases.org/news-events/news/2011-summit

Are Rare Diseases Approaching A Tipping Point?


The summer of 2010 saw remarkable activity related to the development of treatments for rare diseases. The U.S. Food and Drug Administration hosted a two-day public hearing for patient advocates, industry, academic researchers and others to voice their views on current procedures and possible ways to improve them.
The Senate HELP (Health, Education, Labor and Pensions) Committee also hosted a hearing, this one focused on rare pediatric diseases and how to accelerate the development of treatments for them.

New legislation introduced in the U.S. Congress this summer included two bills specifically related to rare diseases—one to remove a roadblock that might keep financially strapped patients from participating in clinical trials (the Improving Access to Clinical Trials Act), and the other to enhance incentives for development of drugs and biologics for children with rare diseases (the Creating Hope Act).

These events and actions might seem small and random to some, but I believe they may signal that orphan product development is approaching a “tipping point”—a point at which change becomes inevitable. And with rare diseases, where only about 200 of the nearly 7,000 known diseases have treatments, and many are not even being studied by researchers, change is a good thing.

Consider other current and upcoming events:

  • A Rare and Neglected Diseases Caucus has just been launched in the U.S. Senate.
  • FDA and NIH, with the help of NORD and Duke University, have created a Rare Disease Investigator Training Course to be offered for the first time in October. The course was “sold out” almost immediately after it was announced.
  • NORD hosted focus groups of key stakeholders and found tremendous interest in rare disease research if appropriate ways could be identified to increase transparency and de-risk the process.
  • FDA created an Assistant Director position to focus specifically on rare diseases in its Center for Drug Evaluation and Research.
  • NORD in the U.S. and EURORDIS in Europe announced a partnership to encourage and facilitate global thinking among patients.
  • Several “big Pharma” companies including Pfizer, Novartis and GSK have recently announced their intention to expand involvement in the rare disease space. While innovative small biotechnology companies should be applauded for all they have done to date, patients also welcome the interest of these larger pharmaceutical companies.

Malcolm Gladwell, who made “tipping point” a household word with his book (The Tipping Point: How Little Things Can Make a Big Difference) published 10 years ago, wrote that in any situation, 80 percent of the work will be done by 20 percent of the participants. These 20 percent, he wrote, are people with enormous gifts for communicating and inspiring.

They are also people who are driven by an overpowering sense of the importance and rightness of their cause. And that’s certainly true of those who are promoting progress in orphan product development on the scientific, advocacy, and regulatory fronts today.

I believe we may be approaching a tipping point in rare disease research and orphan product development. And, if that’s true, it’s wonderful news for the millions of people who have rare diseases for which there is currently no treatment.

When Should Patients Be Given Access to Investigational Drugs?

Investigational Drugs

Seriously ill patients who have exhausted all treatment options often seek access to investigational drugs by way of government-sanctioned “expanded access programs”.  Recently, the U.S. Food and Drug Administration (FDA) implemented new regulations to clarify and increase patient access to investigational drugs.

However, even with the new rules, this topic is more complex than it may seem on the surface.  And it has particular relevance to people with rare diseases since most rare diseases have no approved treatment.

To explore the various sides of this issue, NORD recently co-hosted (with Idis Pharmaceuticals) a media briefing on this topic.  Both NORD and Idis are providers of expanded access programs.

Representatives of FDA, patient organizations, industry, and a university bioethics program spoke from their various perspectives.  They raised some fascinating points in this ongoing discussion.  Some of the things the speakers said were:

  • People with rare diseases are highly motivated to try investigational drugs because they have few treatment options. In fact, there is no approved drug for most rare diseases today.
  • FDA considers access to investigational drugs for treatment purposes important and supports it as long as it doesn’t compromise the clinical trial process and gives appropriate consideration to patient safety.
  • Expanded access programs must be set up in a way that is fair and consistent for all patients.
  • The expense of making drugs available through EAPs can be significant, especially for small start-up companies.
  • Companies may be reluctant to enter into such programs because they may fear that an adverse event could jeopardize their product’s approval.
  • Traffic rules, created for the general good, may be suspended in an emergency, such as when an ambulance is speeding someone to a hospital. Many rare diseases should be considered emergencies.