Patients with hereditary angioedema (HAE) experience recurrent “attacks,” or periods of swelling under the skin. Now, in a Phase 2 clinical trial, researchers are evaluating PHVS416 for patients with HAE. According to Hereditary Angioedema News, PHVS416 is an orally administered “on-demand” therapy to provide relief to patients during an attack.
So what exactly is PHVS416? On the company’s pipeline page, drug developer Pharvaris explains PHSV416 as:
a softgel capsule formulation containing PHA121. Pharvaris is developing this formulation to provide rapid exposure of attack-mitigating medicine in a convenient, small oral dosage form.
PHA121 binds to, and blocks, the bradykinin B2 receptor. Since bradykinin is pro-inflammatory, and causes fluid to leak from blood vessels into body tissue, PHVS416 would prevent the processes leading up to an HAE attack.
Typically, many HAE therapies are injectables. Thus, if PHVS416 shows promise, it would offer an easier and less invasive treatment option. Researchers are exploring this investigational therapy in the RAPIDe-1 clinical trial. During the trial, researchers will analyze PHVS416’s pharmacokinetic properties, safety, efficacy, and tolerability.
Altogether, 54 adults with HAE will enroll in this clinical trial. They will receive either a placebo or a high, medium, or low PHVS416 dosage. Next, researchers will evaluate how well PHVS416 reduces symptoms during HAE attacks. Does it reduce pain and inflammation? If so, by how much? What symptoms are reduced in each dose as compared to the placebo?
Overall, patients will participate in two parts, the first in which they take the dose in the absence of an attack. In the second phase, patients will have to treat themselves over 3 HAE attacks at home, and report the results.
Hereditary Angioedema (HAE)
Hereditary angioedema (HAE) is aptly named: “angio” as pertaining to blood vessels and “edema” as swelling caused by excess fluid in bodily tissue. A genetic defect on chromosome 11 causes HAE attacks, during which severe and unexplained swelling occurs under the skin. Patients with HAE have defective C1-inhibitor protein. Usually, this protein helps control inflammation, coagulation, and protection against disease. But when C1-inhibitor isn’t working correctly, excess bradykinin is introduced into the body. HAE can also be triggered by stress or injury. An estimated 1 in every 50,000 people has HAE. However, females tend to be more symptomatic; this is thought to be a result of hormonal changes.
Swelling can occur throughout the body, such as the face, intestinal tract, throat, or other extremities. During HAE attacks, the fingers and toes, or arms and legs, may swell to 2x their normal size. The eyes may swell shut, or other elements of the face may swell to render someone unrecognizable. Swelling in the intestinal tract may cause nausea and vomiting, abdominal distention, or severe pain. Finally, swelling in the throat can cause difficulty breathing. Additional symptoms may include skin tingling, headache, and fatigue.