Good afternoon. My name is Anna Mazzucco and I’m speaking on behalf of the National Center for Health Research. Our non-profit research center assesses scientific and medical data and provides objective health information to patients, providers and policy makers. Our organization does not accept funding from drug companies, and therefore I have no conflicts of interest.
We know that hypertension is a condition that affects millions of Americans. One in 3 adults has high blood pressure and is at risk for other serious health conditions, such as heart disease and death.
Our medical and scientific experts have carefully reviewed the data provided to you by the FDA and we want to share our concerns:
Data from the pivotal trial showed that the trial’s primary and key secondary endpoints were met. Patients on the highest-dose of the FDC (20/320 mg) had very small but statistically greater mean reductions in DBP and SBP as compared with the highest approved dose of the monotherapy drugs. However, patients in this trial were only treated for 8-weeks. Most hypertension patients require medication for years if not decades. As all of you know, this trial should have been much longer.
We share the FDA’s reservations about the clinical relevance of the small reductions in blood pressure. We question whether approving this combination drug will make a difference in patients’ health.
Is a small improvement worth the risk of adding a second drug? With only 8 weeks of data, it is impossible to say with any conviction that this combination product is safe. That means it is impossible to say whether the tiny benefit outweighs the unknown risks.
And since there is so little benefit, we are especially concerned about the lack of diversity in the efficacy and safety pivotal trials. Most patients were White and younger than 65 years. Blacks are more likely to have high blood pressure compared to any other racial or ethnic group. Adults over the age of 60 are much more likely to develop hypertension as well. But only about 10% of the patients in the efficacy trial were Black and only 9% of both pivotal trial samples were over 65.
This is not an issue of political correctness. Older adults metabolize drugs differently than younger adults. In some cases, such as beta blockers, we know that Blacks tend to metabolize blood pressure medications differently than Whites.
Fortunately, the sponsor conducted subgroup analyses in both trials. The results showed racial differences. There was no difference in blood pressure reduction for Black patients on the combined drug FDC 20/320 compared to patients in the monotherapy 40 mg arm.
Those results indicate that FDC 20/320 does not work for Black patients and should not be approved for them. However, with the small number of Blacks in the different dosage groups, it is impossible to conclude with any confidence that FDC at any dosage is more effective for Blacks than the monotherapy drug alone. If the company wants approval of its drug for non-white patients, they need to study a large number of them to see if it is effective for a generalizable population.
Subgroup analyses in the safety pivotal trial exposed important differences. Although there was a generally low incidence of adverse events across the unfortunately short-term study, patients over the age of 65 in either the experimental group or the monotherapy group were more likely to have bradycardia than younger patients. That’s important information for the label for the monotherapy drug, which is already on the market, as well as the combination drug if it is approved.
- The sponsor has not proven that their drug is safe for patients using it for more than 8 weeks. That is not an acceptable study for a blood pressure medication that would be taken for years.
- The sponsor has not proven this their drug is effective for non-white populations, compared to monotherapy, but preliminary data indicate that it is not effective at the 20/320 dose.
Hypertension is a major cause of death. If FDC is approved on the basis of such weak data, it could potentially harm millions of patients. It is not enough to require post-market studies to answer questions that are essential to answer BEFORE this drug is approved.
Please request longer term data with larger numbers of minority patients BEFORE approving this combination drug.