Starting the second day, the first two speakers spoke about pharmaceutical company involvement in orphan drug development. William Ju, M.D., is the CEO of PTC Therapeutics, a small company founded on the research conducted by Stuart Peltz and Allan Jacobson in Post Transcriptional Control. Some diseases (not HD) are caused by nonsense mutations which prematurely halts the transcription process causing a shortened, nonfunctional protein to be produced. The company has developed a small molecules which can read through the ?stop? codon so that the full protein will be produced. PTC 124 is now in Phase II clinical trials in Duchenne Muscular Dystrophy and cystic fibrosis and has been given fast track and orphan drug status by the FDA. About 10 percent CF cases and 15% of DMD are caused by nonsense mutations.

PTC Therapeutics has involved patient advocacy groups in the development of PTC 124 ? CFF, MDA, and PPMD. Dr. Ju summarized the advantages of patient involvement.

• Concept validation
• Communication with patients
• Access to investigators
• Clinical trial enrollment
• Grant support
• Inspiration

Reijo Salonen, M.D. is from Pfizer, a large pharmaceutical company. He first spoke about how the Orphan Drug Act provides a distinct regulatory framework for the introduction of agents for treating area diseases and has also provided financial incentive to encourage orphan drug development. These incentives include:

• Fast review
• Flexibilty in trial design, conditional approval, smaller patient numbers
• Government contributions
• Price advantages
• Tax incentives
• Exclusivity grant (7 years).

Some of the difficulties involved in orphan drug research include the following facts:

• Endpoints are not well established/accepted
• Regulatory path is uncertain
• Patient selection/diagnosis
• Patient recruitment ? slow processs

Is there hope for rare diseases?

• In practice scientists identify and target disease principles applicable to both common and rare diseases
• Common themes emerge repeated in both common and rare diseases
• Therapies targeting common disease pathways will likely have the greatest impact on rare disease as well

Drug development for Alzheimer?s research is likely to lead to treatments for orphan diseases. Dr. Salonen listed three themes in AD research: mitochondrial dysfunction, protein misfolding, and a misguided immune system. All of these have relevant for Huntington?s Disease.

Sometimes a drug which is developed for one purpose will help an orphan disease. Viagra, which is used to treat erectile dysfunction, also treats the rare and life shortening disease pulmonary arterial hypertension.

Since the Orphan Drug Act was passed about 1300 drugs have been designated. 250 have made it to market About 33 percent of these have come from large companies while 43 have been developed in medium or small companies. About 16 percent have come from the biotech sector.

Huntington?s Disease?s own Dr. Robert Pacific (from CHDI and the High Q Foundation) took advantage of the question and answer period to request access to Pfizer?s library of compound?s. CHDI would take responsibility for assessing whether any had potential in treatment HD while respecting Pfizer?s intellectual property rights ? a win-win situation for all. They agreed to speak further.

The next speaker, Dr. Robert J. Beall, Ph.D. is the President and CEO of the Cystic Fibrosis Foundation. His talk was entitled ?Venture Philanthropy: An option for Drug Development.?

Problem: How do you convince the biopharmaceutical industry to develop drugs for a disease with a population of less than 30,000 patients in the US and 70,000 worldwide?

Solution: Therapeutics Development Program, initiated in 1997 to provide financial and resource support to pharmaceutical partners to encourage development of new drugs for CF. 98 percent f the drugs in the cystic fibrosis pipeline are there because of investment through this program.

The assumptions behind the program are :

• Must have knowledge about the basic defect and underlying pathophysiology of the disease (CF).
• Must work to minimize the risk for partner to enter the field of CF.
• Must establish a business relationship with partner (no necessarily a charitable one).
• Must have ready access to clinical populaton and informational systems to support clinical development. Every patient is registered, and they are able to help locate where the registered patients are.

The Therapeutics Development Network

• Operates similar to High Q
• Coordinating Center is in Seattle,QA
• Operate with their own mail order pharmacy
• Has conducted 36 clinical trials in the last seven years.
• Has available $60 million a year for venture capital
• Works through alliance agreements with partners
• Negotiates awards based on milestones.
• Has a scientific advisory council which includes basic scientists
• Maintains reach in rights ? if a company doesn?t want to procede with development, they can take the work.
• Gets royalties.

As one might imagine, envious audience members asked whether all the money was coming from. $100 million a year is raised through events such as walk-a-thons. Other money comes in from donors. People who used to give $50,00 a year are now giving $5 million because they see the value of the strategic plan. Some money comes in from royalty fees.

About 25 percent of cystic fibrosis patients are in clinical trials.

The next speaker was Michael Zigmond, Ph.D. who spoke on ?Researchers and Advocates: Reaching out to each other? from the perspective of the scientist.

There are good reasons to do this:

• Build base of support
  • Promote public understanding
  • Increase funding for research
  • Improve regulatory environment
  • Attract subjects for clnical tirals
  • Recruit people to serve on advisory boards (e.g. IRBs)
• Educate and motivate researchers
• Inspire youth to explore science careers
• Social responsibility

Scientists can talk to:

• Support groups
• General public
  • Local
  • National
  • International
• Media
• Legislators
  • In DC
  • Most effective at HOME
• Students
• Advocates

Topics can include:

• Disease oriented topics
  • Background to disease
  • Treatments
  • Ongoing research
• Basic science
• Need for research support
• Pass the Starbucks Test
• Make it impossible to ignore research
• We need to make it impossible to say that they
  • Have never heard of the National Institute of Health
  • Can?t name a researcher
• Imagine better health and quality through positive research

Problems in communication include:

• Public attitudes and understanding
  • The majority of Americans support research
  • Most have little understanding of how science works
• Scientific literacy is lacking. Only a small percentage of people know the following concepts
  • Probability
  • Scientific study (23%)
  • Dna (20%)
  • Bacteria 10%
• Balance between simplicity and accuracy
• Responding to desire for short-term fix (we don?t know)
• Communicating through the media
  • Premature reporting (prior to peer review)
  • Getting too much credit ? you credit your colleagues but their names don?t appear
  • Being misquoted
  • Sound bites taken from lengthy interview
  • Nothing actually appearing
• Dealing with medical questions
  • Need to make expertise clear
  • Cannot diagnose on the fly
  • Need to keep entire audience in mind

We must work together because doing so is a win-win-win!