# Presentation: 498953

## How Patients Can Benefit From Molecular Imaging

**Paula M. Jacobs, Ph.D**
**Vice President**
**Advanced Magnetics, Inc**

- April 2005

## How Patients Can Benefit From Molecular Imaging

**Probe basic biological and disease processes in animal models**
**Identify therapeutic targets**
**Identify prognostic factors**
**Provide new clinical imaging agents for**
**Diagnosis**
**Therapeutic stratification**
**Monitor response to therapy**

- April 2005

**Notes:**
	Thank you, Dan, for the opportunity to speak to this group. I am from a small company, so I will only speak a small time.  My perspective here is quite narrow. We don’t do the therapeutic-imaging combinations that have been discussed this morning. Advanced Magnetics develops specific contrast agents that are targeted to normal cellular and organ function, not to pathological tissues.  We have agreements with NCI for clinical investigation of two of our agents, so I am obviously an interested party.
	The NCI is working hard to support the development of molecular imaging and its application to personalized medicine  -- one of the most revolutionary and promising medical advances of the 21st  century. 
	The promise will surely be fulfilled for the basic science aspects, but I have some serious concerns that the clinical promise of molecular imaging agents can be achieved. The scientific barriers to development of new imaging agents can be overcome – but the regulatory and economic barriers have not been effectively addressed.  As several speakers have pointed out this morning, this forum needs to understand these issues.

## MR Agent Development

**$50 M minimum and at least 10 years to develop a single diagnostic indication**
**Reimbursement now around $45/dose**
**Might be able to charge $100-200/dose**
**About 1 million patients a year to even think about breaking even**
**Example:  10-12,000 new high grade glioma patients each year**

- April 2005

**Notes:**
	Here are some very crude numbers for a specific MR contrast agent – and note that diagnostics are very minor in comparison to therapeutics.   Big Pharma will not consider developing drugs that don’t have a potential of at least a half a billion a year in sales.  Small Pharma can work with smaller numbers but we have to have the capital to survive until approval.
	A real example:  there are 10-12,000 new high grade gliomas a year.  We have an agent that has demonstrated preliminary efficacy in diagnosis, evaluation for surgery, intraoperative guidance of resection, and post-operative evaluation of appropriate resection margins, all with a single dose of contrast.  
	Great news, right?  But, no company can afford to commercialize this – CMS will not reimburse thousands for one dose of a contrast agent – indeed the current reimbursement is around $45.  At $50 M to develop, we could never recover the cost of approval of such an indication.

## Barriers to clinical availability of imaging agents

**Small potential patient populations but ever increasing regulatory requirements**
**Expensive pre-clinical & manufacturing investment before trials**
**Unpredictable regulatory climate**
**Difficult reimbursement climate**
****** ****Poor commercial viability **

- April 2005

**Notes:**
	Unless the government gets in the business of manufacturing and selling contrast agents, commercial entities, such as my company, must do so.  But we are economically constrained – a public company has to plan to make a profit, no matter how much we as individuals desire to help patients.
	As the medicine becomes more focused, the patient population for each specific agent becomes smaller and potential sales are reduced accordingly. But regulatory requirements only increase with time and there is no indication that this rate of increase will abate.  Basic regulatory requirements in all drugs, whether therapeutic or diagnostic, now include pediatric studies, QT interval evaluation even if no cardiac issues have been suggested.  In a few years, I predict that genomic stratification will be required for all drugs, no matter how small the target population.  Extensive and expensive pre-clinical toxicology and pharmacology as well as manufacturing/ stability programs must be completed with each unique agent prior to human studies.  
	Few drugs that begin this process proceed to human trials and few of those that proceed to initial trials are ever commercialized.  Many fall by the way for safety or efficacy reasons, but many also for fail for regulatory and economic reasons. 
	One of the biggest barriers at this time is the unpredictability of the regulatory process.  With the required time scale of development, unpredictability is devastating to commercialization of marginally profitable drugs like contrast agents. Phase 3 trial designs must be finalized many years before submission of the results – and prospective trials cannot be changed mid stream.  Many sponsors have consulted with FDA over months to years and agreed on trial design, statistics, and end point.  But when the endpoint is met several years later, the sponsor is informed that some other endpoint is now required, as has been the case with several recent contrast agent reviews. Consider as well the march of technology – we can hardly do trials now to use the 7T scanners that may be common 8 years from now. The path to approval is impossible to plan.  Drug companies are now quite reluctant to develop marginally profitable diagnostic agents when they can have no assurance that agreed upon program will be acceptable 5-10 years after initiation. 
	As for reimbursement, our economics may dictate that a contrast agent can only be viable if we can charge thousands of dollars a dose, but CMS now reimburses $44 a dose....
Here is the challenge to this forum: 

## What can we do to make these targeted imaging agents available to small but important patient populations?

- April 2005

**Notes:**
Thank you for your attention.