From The Editor | January 4, 2017

Lexicon Uses Patient Input To Support Primary Endpoint

Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

Lexicon Uses Patient Input To Support Primary Endpoint

When Lexicon Pharmaceuticals began planning for a clinical trial on neuroendocrine tumors, there were two things it hoped to accomplish. First, it wanted to incorporate patient voice into the trial design. Although Lexicon is a small company without a large budget for patient outreach, knowing what symptoms were most important to patients was critical to designing an effective trial. Second, the company wanted to incorporate some type of mobile technology into the trial to help track feedback from patients.

“Today we have new mobile devices to help us get all types of data from patients,” says Pablo Lapuerta, EVP and chief medical officer for Lexicon, who will be speaking on this topic at the 2nd annual Data & Technology in Clinical Trials USA conference in February. “The problem is we do not always know how to properly interpret that data.”

For example, Lapuerta notes he recently spoke to a physician about how a medicine could help his patients. The doctor suggested giving all of them Fitbits. That device could measure the steps a patient takes in a day, and we know the average American male takes 6,000 steps per day.

“If a patient has a change in step count from 6,000 to 6,500, is that good?” asks Lapuerta. “If the steps for a sick patient changes from 3,000 to 3,500, is that good? It can be difficult to answer those questions. When working with mobile devices, I think we need to be prepared to properly interpret the data we are getting. The best way to do that is to stay close to the patient.”

Gather Patient Reported Outcomes

Lexicon is awaiting approval on a program it designed for patients with neuroendocrine tumors. This is a rare cancer around which little data has been published. Lexicon is working on a subset of that group: Cases where the tumor produces excess serotonin resulting in intestinal problems that include pain, cramping, bowel control, and diarrhea.  

“We started recording bowel movement frequency in patients and had some evidence the drug was reducing it,” says Lapuerta. “Some literature we reviewed indicated reducing those bowel movements might be important to patients, but what really helped us to better understand the symptom was interviews we conducted with patients taking part in a Phase 2 study. That input allowed us to gain real perspectives into how reducing that frequency was improving lives, sometimes in quite dramatic ways.”

In a new drug application (NDA) presented to the FDA, Lexicon stated that reducing bowel movement frequency by just 30 percent made a real difference in the lives of patients. A subsequent Phase 3 trial gathered additional evidence. Responder analyses (where each subject is classified as either a 'responder' or a 'non-responder') were used to provide confidence that the change produced by the drug was not just statistically significant, but clinically meaningful.

Electronic diaries (eDiaries) were used by patients to record the data. Lapuerta notes the data is collected and can become significant very quickly because the data is so precise. The NDA is currently in the hands of the FDA and Lexicon hopes to have an answer soon.

Select The Right Primary Endpoint

There is a lot of data Lexicon could have collected from patients, and prioritizing primary endpoints was certainly a concern for the company. For the regulatory agencies, Lexicon also had to address why bowel movement frequency would be the primary endpoint. In fact, the FDA even asked Lexicon if stool consistency shouldn’t be the primary endpoint.   

“We had to answer that question and used the patient voice to do so,” says Lapuerta. “The interviews we conducted in Phase 3 asked patients, ‘Of all the symptoms you have, which one is the most important for us to treat.’ The most cited response was bowel movements that occurred too frequently.”

Patients were then asked a direct question: “What is more important to you, reducing bowel movement frequency or improving your stool consistency?” A majority of patients again cited bowel movement frequency. Those types of responses can be relevant to regulatory agencies and pharmaceutical companies.

Lapuerta states the effort was about meeting the needs of the patients. Lexicon wanted the surveys to be rigorous, and not simply a marketing exercise. The responses had to support the primary endpoint and have clinical relevance. The interviews were done over the phone. To ensure the results would be relevant, patients had to agree, in advance, to accept the phone call and be interviewed after 12 weeks of treatment. Lapuerta found patients were very eager to discuss their results. The interviews produced a good, unbiased sample of individuals whose characteristics reflected the patient population.

“Many companies will say they are inspired by patients,” says Lapuerta. “We went beyond that and changed what we do. We did not have a huge budget, a patient centricity officer, or an advisory board with patient representation. It is difficult to have those luxuries in a small company. But by engaging with patients and getting them to agree to these interviews, we were able to find a way to hear their voice and incorporate it into our clinical research program. The fact that this was a rare disease means we had to really understand the condition even before we could begin to understand the patient. The data we collected did not have historical benchmarks. Therefore, we had to show that the data we collected was meaningful. The feedback from the patients made it clear that the results mattered to them.”      

If you would like to hear more about Lexicon’s use of patient input and mobile devices, plan to attend the eyeforpharma 2nd annual Data & Technology in Clinical Trials USA conference. It will be held February 21-22, 2017 in Philadelphia, PA. Click here for more information, and use the code ClinicalLeader200 to save $200 on your registration.