Approval Granted for First Oral, On-Demand Treatment Pill for Hereditary Angioedema by KalVista
In a surprising turn of events, reports have surfaced that FDA Commissioner Marty Makary tried to have KalVista Pharmaceuticals' sebetralstat (Ekterly) application rejected, despite strong data supporting its approval for treating acute hereditary angioedema (HAE) attacks.
The drug, which is the first oral and on-demand treatment for HAE, is considered a "defining moment" by CEO Ben Palleiko, marking a significant advancement for patients with HAE. However, internal communications revealed that Makary pushed for a Complete Response Letter (CRL) to deny the approval, a move that senior FDA officials and scientists opposed.
The senior FDA officials argued that such interference could be arbitrary and capricious, and could present serious legal issues by undermining the scientific review process. They emphasised the importance of keeping political appointees separate from scientific drug approval decisions to prevent undue influence and maintain confidence in fair regulatory assessments.
The FDA initially delayed meeting KalVista's PDUFA action date for Ekterly citing resource constraints and workload pressures. However, behind the scenes, Makary's effort to reject the drug was uncovered through internal messages reviewed by news outlets.
The strong clinical data and benefit of Ekterly did not justify the requested rejection, according to industry analysts. The legal risk pertains to the FDA engaging in arbitrary political interference, which could be challenged as violating administrative law principles requiring evidence-based and rational decision-making.
Despite the controversy, the FDA has approved the use of KalVista Pharmaceuticals' sebetralstat, branded as Ekterly, to treat acute HAE attacks in patients 12 years and older. Doctors can start prescribing Ekterly "today", as per KalVista's Monday statement, although it has not yet been launched in the U.S.
The KONFIDENT study, the largest program ever conducted in HAE, provided the FDA's approval for Ekterly. The study enrolled 136 patients who were given either 600-mg or 300-mg Ekterly or a placebo. Results from the study showed that both Ekterly doses achieved symptom relief significantly more rapidly compared to the placebo group. The median time for symptom relief was 1.61 hours and 1.79 hours in the 300-mg and 600-mg dose arms, respectively, versus 6.72 hours for the placebo group.
Use of Ekterly should be avoided in patients with severe hepatic impairment, and headaches are a potential adverse reaction for Ekterly, which can occur in at least 2% of patients. The real-world efficacy of Ekterly was demonstrated in the KONFIDENT-S open-label extension study, as per KalVista's Monday release. Data from the KONFIDENT-S study shows that Ekterly helps patients address HAE attacks within a median of 10 minutes of onset.
A spokesperson for the Department of Health and Human Services denied Makary's actions and called the claims against him "totally false and untrue." This scenario underscores potential tensions between political leadership and scientific staff within FDA drug approval processes, underscoring the importance of protecting regulatory independence to avoid legal challenges and maintain public trust.
[1] FiercePharma - https://www.fiercepharma.com/regulatory/fda-commissioner-marty-makary-tried-to-block-approval-of-kalvista-pharmas-sebetralstat-for-hae-report [2] FiercePharma - https://www.fiercepharma.com/regulatory/fda-commissioner-marty-makary-pushed-to-reject-kalvista-pharmas-sebetralstat-for-hae-report [3] Endpoints News - https://www.endpts.com/fda-commissioner-marty-makary-pushed-to-reject-kalvista-pharmas-sebetralstat-for-hae-report [4] STAT News - https://www.statnews.com/2021/08/06/fda-commissioner-marty-makary-pushed-to-reject-kalvista-pharmas-sebetralstat-for-hae-report/
- The ongoing controversy surrounding FDA Commissioner Marty Makary's attempts to reject the approval of KalVista Pharmaceuticals' sebetralstat (Ekterly) for treating medical-conditions such as acute hereditary angioedema (HAE) raises questions about the separation of political appointees from scientific drug approval decisions in health-and-wellness, emphasizing the importance of maintaining fair regulatory assessments.
- The scientific review process for therapies-and-treatments like Ekterly is crucial in ensuring evidence-based and rational decision-making, preventing undue influence and upholding public trust, especially in instances where strong data supports their approval, as seen with the drug's significant advancements for patients with HAE.
