The Orphan Drug Act Almost Failed to Clear the Launch Pad Before Achieving so Much for Patients!

January 31, 2023By Frank J. Sasinowski

In early 1984, a year after President Reagan signed the Orphan Drug Act into law, the FDA was not seeing the anticipated avalanche of requests for orphan drug designation.  At that time, new Federal laws on drugs were far and few between.  FDR signed the 1938 law that required that drugs be safe & JFK signed the 1962 law that required that drugs also prove they have a benefit.  So when patients led by Abbey Meyer and Marjorie Guthrie (Woody Guthrie’s widow) had championed the 1983 law to create incentives for developing drugs for those with rare conditions, the FDA was excited at this once-in-a-generation new law as this was FDA’s 3ed major drug law in nearly half a century.  FDA created a new office directly under the Commissioner and promoted FDA’s drug center director, Dr. Marion Finkel, to lead this new Office of Orphan Products Development.

Now in early 1984, after a year of anticipation, nearly nothing was happening, but for a handful of therapies that had been in development and were the poster children for the “patients’ campaign” that had led to the new law.

The Deputy Commissioner of FDA, Dr. Mark Novitch, went to Phil Paquin, leader of drug policy which then was in the Office of Compliance in the Center for Drugs and Biologics (yes, a single Center at that time) and asked Phil to try to figure out why the new law was not seeing the expected kind of activity.

Phil called a very new regulatory counsel (my title) into his office and asked me to tackle this.  Realizing that this was a huge opportunity and I was green and that Phil’s office had many seasoned & excellent regulatory counsel like Steve Unger (who led the IND Rewrite & later became FDA Ombudsman) and Mike McGrane (who led the NDA Rewrite, revising the entire set of regulations on NDAs that is now Part 314 of Title 21 of the Code of Federal Regulations), I replied that someone with more seniority and experience may be better equipped for this assignment.  Phil however insisted that he wanted me to take this on & by myself.

I read the provisions of the new law and saw two provisions that seemed to be possible stumbling blocks that could be frustrating uptake of the new law: (1) a provision required that to be designated an orphan drug, a sponsor had to prove that it could not recoup its research & development costs during the 7 years of market exclusivity— essentially a government provided monopoly on marketing; and (2) another requirement for being designated was that the drug could not be capable of being patented.  (I suspect that this may have been included because some may have argued that if there was patent protection for an orphan drug, there would be no need for the 7 years of orphan drug exclusivity).   Well, while my reading of the new law revealed these as two possible barriers to industry embracing the new law, yet what to do about these?

First, I was surprised to learn that FDA had economists, and the senior economist, Rus Scarato, was happy to help me craft language to guide sponsors who were unsure how to prove that economically they would be incapable of recouping R&D costs over a 7 year period of monopoly marketing.  (Later I was asked to draft the regulations to implement the new law , which is another story and which was accomplished only with the adroit collaboration with a colleague, Emery “Rico” Sturniolo.  See 21 C.F.R. § 316.21(c) for the language explaining how to verify that R&D costs could not be recovered by US sales.)

Second, FDA did not and still does not have any patent law expertise in-house but our sister agency, NIH, did and does, and so I worked with NIH patent counsel to come up with a sample affidavit that a corporation’s patent counsel could provide to FDA that would affirm that the drug in question could not qualify for a US patent.  Of course, no patent counsel “worth their salt” would ever WANT to make a statement against their interest that they were incapable of coming up with any possible way to show that this drug’s use in treating a rare condition was indeed “new” and “not obvious”.

Armed with this as my view of the two possible reasons the new law had not taken off as FDA had expected, and armed also with my two possible solutions, neither of which seemed to be wholly satisfying to industry (for what company wants to open its “books” to the government on all of its costs & projected revenues and what patent counsel wants to give a statement to the government that it can not figure out any way to argue for a patent on some aspect of a drug’s use for a rare disease), I went to see Dr. Finkel in her office.

I sat down on the opposite side of her large wooden desk, across the table from this soft-spoken person who was regarded by everyone as one of the best leaders and thinkers inside FDA and explained to her that I thought I had figured out why companies were not beating a path to her office and also come up with possible solutions.   Dr Finkel listened and after hearing me out, she picked up her black, rotary dial phone on her desk, called someone, and what I heard next was: “Henry, we think we have some issues with your new law but we also think we have solutions.” And she handed me the phone without explaining who she was talking to.  The person on the other end was Congressman Henry Waxman, the “author” of the Orphan Drug Act.  I explained again the two possible issues or impediments and two possible yet unsatisfactory solutions, that were nevertheless my best attempts at fixes to each problem.

Abbey Meyers, Rep. Henry Waxman, Senator Nancy Kassebaum, and Dr. Finkel then came up with much better solutions than mine!!!  Thanks GOODNESS!  They came up with the 1984 and the 1985 amendments to the Orphan Drug Act which removed the requirement that to be an orphan drug one could not be patentable and which created a simple 200,000 persons diagnosed with the rare condition as the alternative criterion for qualifying to be an orphan drug.  (The economic pathway was not eliminated but left as an alternative that has almost never been used…perhaps fodder for one of many, nearly countless possible follow-up stories to this first one!).

The singular lesson that I draw from my initial baptism into the field, as well as from my 40 years of working to address the suffering of our sisters and brothers with rare conditions, is this: There is an incredible “Power of One!”

All my experience is this field tells me over and over again how much each one of us can do.  Each person is incredibly powerful in this arena.  Dr. Novitch, Dr. Finkel, Mr. Paquin, Mr. Sturniolo, Mr. Scarato, NIH patent counsel….these public health service servants of all Americans.  Abbey Meyers, Marjorie Guthrie, Rep. Henry Waxman, Sen. Nancy Kassenbaum….patient advocates and those in Congress (both members and their staffs) who marched and worked to create this new law and make it work.   Untold numbers of researchers in academia and in industry.  Investors who back this kind of longshot research when many others would say “smart money” should go where the biggest markets are.  Individuals who’s lives were changed by a family member, usually a child, who just happened to be unlucky in the spin of the genetic roulette wheel, and who left everything else and devoted their careers to helping their child and all others similarly affected, heroes to me like Martine Rothblatt of United Therapeutics, John Crowley of Amicus and Matt Wilsey of Grace Science and that list could go on and on and on.

My lessons learned from four decades is this: You too are whoever you are and Whatever your position….Know that you too have incredible abilities to effect real change by doing what you can.  Know that.  Act on that.  IT is REAL!  Onward, onward, ever onward!

Categories: Orphan Drugs