My name is Dr. Margaret Dayhoff-Brannigan and I am a senior fellow at the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from pharmaceutical companies, and therefore I have no conflicts of interest.
Thank you for the opportunity to speak here today.
I completed my Ph.D. in Biochemistry and Molecular Biology at the Johns Hopkins School of Public Health. I bring a perspective as both a researcher and an advocate for public health here today.
Long-acting beta-agonists have a history of serious adverse events in asthma patients including a four-fold increase in asthma-related death. So, let’s start with the assumption that we don’t want a new LABA on the market unless we have good evidence about safety and efficacy.
The data presented by GlaxoSmithKlein indicates that Breo Ellipta has a similar safety profile to other combination Inhaled Corticosteroid/long-acting beta-agonists. The sponsor submitted pooled analysis from 18 clinical trials for safety information. However, only 5 of these trials had relevant treatment and control arms. Furthermore, two of those trials were only 12 weeks studies – less than half the time of the 26 week trials conducted for safety of previous LABAs. There were only 3100 patients across the three longer-term studies, which is significantly less than the 25,000 or more patients included in safety trials for one of the other approved LABAs, Salmeterol.
So we have less safety information about this new drug than we have about other LABAs. It would be unethical to approve the product based on this data unless there were clear evidence that this product was much more effective and therefore met an urgent, unmet need. So, let’s look at efficacy data.
Let’s start with children ages 12-17, because the data are clear. Several trials of 12-17 year olds show that inhaled corticosteroids alone were more effective than Breo Ellipta, the new combination ICS/ Vilanterol product that you are considering today. It would therefore be unethical to risk these children’s lives by giving them a drug with no proven benefit in asthma control.
So, to answer the question FDA has posed: there is no evidence that Breo Ellipta should be approved for children ages 12-17.
There is also a major concern about this drug for African Americans of all ages. Safety studies on other approved LABAs have shown an increased safety risk for African Americans. For this new product, there are too few African Americans in any age group in the study to be able to say whether or not it is safe or effective.
African American children have the highest prevalence of asthma in the United States, and these children are more likely to have uncontrolled asthma. Asthma is also common among Black adults. The lack of Black patients in these studies should be unacceptable to the FDA and to this Advisory Committee. Given the potential risks and lack of data, you should recommend against approval of Breo Ellipta in the African American population of any age.
One of the studies compared Breo Ellipta to another already approved drug, Advair, and found no statistically significant difference in safety or efficacy between the two. However, the trend favored Advair providing better control of asthma. Since Breo Ellipta is not more effective at treating asthma than already approved products and could be less effective, it certainly does not meet an unmet need.
Since the data provide very little information about safety, additional safety studies should be required by the FDA BEFORE approval for Breo Ellipta to prevent patients from being put at additional risk by this new drug that has no known advantages but has unknown risks.
In light of all these issues and unanswered safety questions, I respectfully ask you to recommend against approval. It does patients no favor to approve a new drug with no known benefits and with unknown risks. More information is clearly needed on the long term safety of Breo Ellipta as a combination product for asthma patients. This information must be obtained prior to approval.
However, if the FDA were to put patients at risk by approving this drug, Black box warnings and long term safety trials should be required, as they have been for other LABAs. And, the black box warning for this product should be expanded to reflect the additional risks and lack of efficacy for African Americans.
In conclusion, we don’t know if this LABA works as well as others on the market. There is no urgent unmet patient need for this drug, therefore appropriate safety and efficacy trials should be conducted before approval. We urge the FDA to require pre-approval studies lasting at least 26 weeks that are sufficiently powered to examine subgroups such as 12-17 year olds and African Americans for BOTH safety and efficacy.
Thank you for your time.