Kalvista drug has received FDA approval to treat acute swelling attacks in rare diseases
In rare diseases, hereditary angioedema or HAE, painful swelling attacks can occur anywhere in the body without warning. Drugs can be used for acute treatment of these attacks, but they are all administered by injection or infusion – heavy dosing methods, especially for young patients. The FDA approved the Kalvista Pharmaceuticals pill, making it the first oral therapy to treat acute attacks caused by HAE.
The regulatory decision announced on Monday covers the use of the drug in patients aged 12 and over. The pill, known in development as Sebetralstat, will be sold under the Ekterly brand. Approval was three weeks later than expected. Last month, the Cambridge, Massachusetts-based company revealed that the FDA will not meet that deadline due to “FDA resource restrictions.” Kalvista said its new product is the first in biotech and will be launched immediately.
“This is the first time patients can receive oral on-demand treatment, providing opportunities to change the way of attacks and when to treat them,” Calvesta CEO Ben Palleiko said on a conference call Monday morning.
HAE is a genetic disease of hereditary deficiency or dysfunction of C1 esterase inhibitors, a protein that controls proteins associated with swelling and inflammation. The lack of C1 esterase inhibitors leads to uncontrollable activation of the Kallikrein-Kinin system, which in turn leads to swelling attack characteristics of HAE. These attacks can occur throughout the body. They can be life-threatening when they affect the patient’s face and airway.
Drugs currently available for the treatment of acute HAE challenge include two C1 esterase inhibitors, ruconest of the drug group and Berinert of CSL Behring. Takeda Pharmaceutical Markets Kallikrein inhibitor Kalbitor and Bradykinin inhibitor Firazyr, both used for acute treatment of HAE challenge. All of these drugs are administered by injection. Biocryst Pharmaceuticals sells Kallikrein’s former oral inhibitor, a protein that plays a role in HAE swelling attacks. BioCryst drug Orladeyo is only used to prevent HAE attacks in patients aged 12 and over.
Kalvista’s Ekterly is an oral small molecule Kallikrein inhibitor. In a Phase 3 test supporting the FDA submission, the results showed that the drug was faster in relieving symptoms, reducing attack severity and attack resolution compared to placebo. In an open-label extended study, Ekterly enabled patients to treat their acute HAE challenge within the middle of 10 minutes of attack. These latest results suggest that the median attack involving the larynx and abdomen is a median of 1.3 hours, as well as a breakthrough attack in patients receiving long-term prevention HAE prevention treatment. The most common adverse reaction reported in clinical testing is headache.
Ekterly’s prescription information indicates that the patient is taking a two-pill dose under the first sign of HAE challenge. If the initial dose is insufficient or symptoms recover or worsen, the second two-plate dose may be taken three hours after the first dose. Kalvista will be available in a package containing two doses or four tablets Ekterly offers. The wholesale price of Kalvista is $16,720 per dose, which means a package costs $33,440. In contrast, other branded products for acute HAE treatment costs between $11,000 and $17,000 per dose.
“We have priced the competitiveness of existing brand therapies in the HAE market,” said Chief Business Officer Nicole Sweeney. “We believe that this pricing reflects the innovation we bring to the community and will support widespread utilization.”
Ekterly’s clean label opened the product to address a wide range of HAE patients, said Joseph Schwartz, an analyst at Leerink Partners, in a note sent to investors.
“Because it has long been the pill of Hae’s Holy Grail to treat attacks, we see Ekterly’s endorsement as a paradigm shift in the landscape,” Schwartz said. “Ekterly has injectable efficacy, and a convenient oral route should allow early treatment and treatment of all HAE attacks.”
In Europe and Japan, Ekterly remains under regulatory scrutiny. The Leerink program will receive peak sales of approximately $470 million in the United States and Europe for acute HAE treatment. The drug can find other diseases that are used to benefit from Kallikrein inhibition. It can also expand its current label in HAE. Kalvista is conducting a pivotal study evaluating Ekterly’s oral tablet formula for the treatment of HAE challenge in patients aged 2 to 11 years.
The competition with Ekterly may come from Pharvaris, which is undergoing critical testing with Deucritictibant, a Bradykinin B2 receptor antagonist formulated in once-daily capsules. Pharvaris performed two phase 3 tests, one for acute HAE treatment and the other for HAE prevention. The Netherlands-based company said Deucrictibant’s extended release formula allows its medication to maintain therapeutic contact in the body for more than 24 hours, potentially addressing the possibility of HAE attack in a single dose.
Photos of Calvesta Pharmaceuticals
