Does The First-Patient-In Milestone Really Matter?

By John Carlos Diaz, GeoSera Consulting

Have you heard someone say, “We have to press forward as fast as possible to meet the first patient in (FPI) to the trial”?

I am confident 99.99 percent of my clinical research colleagues are raising their hands or nodding their heads at their desks, laptops, or mobile devices.

Usually the directive to meet the corporate milestone comes from C-Level leadership that is far removed from R&D or someone who does not have experience in drug development. I have worked for multiple diverse types of pharma companies, large and small pharma, U.S.-based and global companies, and each company has whipped the clinical teams to meet paramount FPI milestones. Timelines are truncated, research sites and operational activities are not thoroughly vetted, and study design and protocol development are rushed in order to meet the magical corporate milestone.

I have always heard, “The FPI date is important to our company’s stock price, investor confidence in our company, and our public reputation.” The FPI milestone has been the one constant in my variety of experiences. I now believe that, no, the FPI date does not matter when compared to delivering a properly executed trial that meets the primary endpoints. Sorry, pharma executives. We have all been duped for years that the FPI milestone yields an increase in stock price and company value.

Below is a tabular representation of data I found that supports the claim that the FPI date does not affect a company’s stock price. (Companies were selected at random.)

I used the parameters below to ensure a true “apples-to-apples” comparison between each company’s respective stock price:

1. All companies were in the CNS therapeutic area (TA) with varying sub-TAs within CNS.
2. All companies had their FPI within the past four years.
3. Stock price on FPI was compared to the stock price on last patient out (LPO).
4. Stock price on FPI was compared to the stock price after results were made public
5. Small pharma companies only, less than 1,000 employees.
   1. A Phase 3 hit or miss has a greater impact on a small pharma company with a limited pipeline because if there is a negative trial or “miss,” investors lose interest in the small company.
   2. A Phase 3 miss at a larger pharma company is more easily absorbed into the company’s stock price when there are other products in the pipeline that can keep investor interest in the company alive.
6. The FPI and LPO, month/year, were gathered from public trial registry data.
7. The stock price three months prior to FPI was three calendar months and on the first day of the month, prior to FPI.
8. I obtained the stock price on the first day of the month for FPI and the last day of the month for LPO.
9. All trials were pivotal, Phase 3, randomized, placebo-controlled trials to measure efficacy.
10. Company names were removed to keep the name of the company blinded.

Discussion

The stock price of companies 1 through 8 varied throughout the course of the trials. Measuring the stock price during the trial was not part of the discussion because there are variables that can occur during the trial that are impossible to track due to the confidential nature of how the study is conducted.

The negative results for the pivotal trials for companies 1 to 4 caused their stock prices to drop 13 to 82 percent of each company’s respective FPI stock price.  Companies 2 to 4 lost over 60 percent of their stock price after the negative results were posted, which is crippling to small companies. When the stock price is so low, funding is harder to obtain, and financing future trials to dig themselves of their financial holes will become incredibly difficult. Company 1 lost only 13 percent of their FPI stock price when the negative results were announced, but when you look more closely, the negative result for company 1 made the stock price drop 71 percent from the stock price at LPO. LPO for company 1 was a few months prior to the negative results were announced, so company 1 lost 71 percent of their value within a matter of months.

Once the positive results from companies 5 to 8’s pivotal trials were made public, these companies’ stock prices increased from 15 to 391 percent. A positive trial means there is a better chance the FDA or any regulatory agency will approve a drug for marketing purposes, thus generating sales and revenue for a company. Revenue leads to investor confidence and thus increases the stock price and company’s financial health.

When corporate goals such as FPI are defined, the FPI date should only be considered as goal to keep the study team focused on a future target date. Achieving the FPI milestone should only occur after the operational activities, study design, and protocol development are thoroughly reviewed and understood. Too many times throughout my career I have seen trials derailed by rushing toward the FPI date without thinking through each step of a protocol and how it affects the endpoints of the trial. In CNS trials, one of the most common reasons trials fail to meet the efficacy endpoint is the placebo effect. Proper planning in maintaining the blind, statistical designs, and randomization rates are ways to reduce the placebo effect. Often, these details are overlooked or trivialized during trial setup, so the team can focus on meeting the magical FPI milestone.

Obviously, at some point the trial must start. So, we cannot delay FPI inevitably, but when the FPI date is listed as a corporate milestone, the study team should have enough time to properly vet all potential risks that could yield a failed study.  

Conclusion

In this small-scale investigation, the FPI milestone did not matter for overall stock price. In fact, based on the table above, it appears to negatively affect the company’s stock price. Only one of the eight companies had their stock price increase when FPI occurred when compared to the stock price three months prior. Further investigation is needed to determine why a specific company’s stock price dropped at the FPI milestone.

I originally postulated that the LPO date was more valuable to a company’s stock price, but after tracking the stock prices throughout the duration of the pivotal, Phase 3 trials I found that I was mistaken. The stock price at LPO barely moved, except for two of the eight companies I researched.

It is clear the FPI milestone does not matter to a company’s stock price. The results of the trial are what increases/decreases stock price and should be the most valuable milestone for a company. When the FPI milestone is created, propose a date that is achievable without sacrificing the quality of the study design, protocol, and operational activities so the team can achieve the milestone that truly matters … a positive trial.

About The Author

John Carlos Diaz has been in the pharmaceutical industry for 18 years with operational experiences ranging from preclinical drug metabolism and pharmacokinetics (DPMK), clinical pharmacology/Phase 1, adult/pediatric, global Phase 2 to 4, and investigator-initiated trials for both large and small pharma. Currently, John Carlos uses his clinical research experience to benefit pharma/biotech companies, clinical research sites, clinical trial service providers, and CROs. You can contact him via email or connect with him on LinkedIn.