True NORD

The Avastin situation raises a lot of issues – not the least of which is the future of reimbursement for expensive treatments (both on and off label) for not only cancers, but also rare diseases.

First some facts, figures, and definitions:

• A “rare disease” (according to the IOM) is one that affects fewer than 200,000 people (in the United States)
• An estimated 25-30 million Americans suffer from a rare disease
• According to the NIH Office of Rare Diseases, there are more than 6800 “rare diseases”
• 80% of rare diseases are of genetic origin
• 50% of rare diseases affect children
• 85-90% of rare diseases are life threatening

And, most germane to this conversation …

• Only 10% of rare diseases have available treatments

So, what are we doing about it?

Well, of course there’s the Orphan Drug Act of 1983 which:

• Modified the Food Drug and Cosmetics Act to increase market incentives and reduce regulatory barriers for orphan drugs
• Provided the following incentives for industry to research, develop, and manufacture drugs for rare diseases:
• Seven years market exclusivity from the date of marketing approval of a drug with an orphan designation
• Tax credit of up to 50% for clinical research costs of a designated orphan drug
• Grants to support clinical development of products for use in rare diseases
• Waiver of PDUFA fees normally charged to sponsors
• Assistance with trial design for sponsors by FDA staff about nonclinical and clinical studies that could support approval of a rare disease drug

And the FDA Modernization Act of 1997 which:

• Provided additional incentives for industry to develop drugs for serious or life threatening conditions and which potentially address unmet medical needs (not exclusive to orphan drugs) including fast track, accelerated approval, and priority review designed to facilitate the development and expedite the review of new drugs that fall in the above category.

And what have these well-meaning pieces of legislation delivered?

Well, as of January 2011:

• There are 460 rare disease drugs in development in late stage clinical trials or awaiting FDA approval
• More than 350 medicines have been approved to treat rare diseases since 1983 (compared to 10 in the 1970s
• 2,313 medicines have been designated orphan drugs by the FDA
• Between 2000 and 2008:
  • Orphan drugs comprised 22% of all new molecular entities (NMEs) and 31% of all significant biologics (SBs) receiving market approval
  • Orphan drugs receiving priority review status rose from 35% of all orphan NMEs in 2000 to 50% in 2008; orphan SBs receiving priority review status rose from 17% to 67%
  • Big Pharma’s share of orphan drug approvals grew from 35% to 56%
• Average total development time for orphan products dropped by 2.3 months for NMEs and 37.5 months for SBs

Mazel tov. All good things. Solid and important achievements – as intended.

Why the success? Many reasons – not the least is which is that investment in innovation was rewarded.

But now comes the unintended part – reimbursement problems.

Scuttlebutt across the industry is that payers are beginning to, increasingly, question Tier One formulary status for many new drugs designed (and designated on label) to treat rare diseases. And these conversations are, increasingly, taking place well in advance of FDA review. The result is that Big Pharma is (increasingly and not surprisingly) recalibrating go/no-go decisions on rare disease development programs. It’s yet another unintended (and dire) consequence of short term cost-centric care trumping patient-centric medicine.

Stifling for innovation. Worse for patients.

Widows and Orphans is not an option.

Attention must be paid.