goes underdiagnosed and/or undertreated. Types of periodic paralysis are differentiated by criteria including underlying genetic mutations and changes in blood potassium during an episode. The two most common forms of PPP are hypokalemic, when episodes can be induced by low blood levels of potassium, and hyperkalemic, when episodes are associated with elevated levels of blood potassium. We believe, based on our market research, that there are approximately 4,000 to 5,000 patients in the United States diagnosed with PPP. Keveyis Features and Benefits Keveyis is an oral carbonic anhydrase inhibitor that was approved by the FDA in the United States in August 2015 to treat hyperkalemic, hypokalemic and related variants of PPP. The exact mechanism(s) through which oral carbonic anhydrase inhibitors, and Keveyis in particular, decrease the frequency and severity of periodic paralysis attacks is unknown. However, it is believed that their effects are mediated both locally (i.e., in muscle) and systemically. It is not known whether their effects are disease-modifying. Keveyis has received orphan drug exclusivity status in the United States through August 7, 2022. Keveyis has been studied in two separate double-blind, placebo-controlled multi-center studies and proven to be an effective treatment for PPP. Keveyis was shown to decrease the number of PPP episodes. In addition, episodes that did occur were shorter in duration and not as severe. The most common adverse reactions with incidence ≥10% and rates greater than placebo in patients treated with Keveyis were paresthesia, cognitive disorder, dysgeusia, and confusional state. Less than 10% (3/36) of all patients treated with Keveyis in one study withdrew due to an adverse reaction in the double-blind phase; 17% of hyperkalemic patients (2/12) and ~4% (1/24) of hypokalemic patients discontinued treatment. Keveyis Market Potential We believe, based on our market research, that there are approximately 4,000 to 5,000 patients in the United States diagnosed with PPP and we believe that we can address the market by targeting physicians who are managing patients with PPP, including neuromuscular specialists, general neurologists and primary care physicians. Keveyis Commercial Strategy Our commercial strategy for Keveyis is to promote its unique benefits, as well as a concerted effort to raise awareness about the underlying PPP disease among the physician/patient/caregiver community with the goal of increasing the rate of diagnosis when the symptoms may otherwise be overlooked. In addition to a specialty sales force, we established a field-based group of patient access managers and medical affairs liaisons. We use a single, specialty pharmacy to provide reimbursement, clinical and distribution support for Keveyis and to develop cost-sharing and patient assistance programs to support qualified, commercially insured patients, federaland state-insured patients, and uninsured or under-insured patients. We also donate money to independent charitable foundations dedicated to this cause. Our ultimate goal is to ensure that no PPP patient is denied access to Keveyis for financial reasons. We work with the patient community to advocate for patients improving diagnosis, genetic testing and treatment. Recorlev Recorlev (levoketoconazole), the pure 2S,4R enantiomer of the enantiomeric pair comprising ketoconazole. Recorlev is a nextgeneration steroidogenesis inhibitor. The active pharmaceutical ingredient in Recorlev, levoketoconazole, exerts its primary therapeutic effect by blocking the synthesis of cortisol in the adrenal glands, leading to the reduction and, ideally, the normalization of blood cortisol. Levoketoconazole has been granted orphan drug designation by the FDA and the EMA for the treatment of endogenous Cushing’s syndrome. Levoketoconazole inhibits the cortisol synthesis pathway at several points. Based on the results from our SONICS and LOGICS clinical trials, we believe that Recorlev can have a beneficial impact on hypercortisolism, the hallmark of endogenous Cushing’s syndrome, as well as benefits related to several comorbidities of endogenous Cushing’s syndrome, including those associated with cardiovascular disease risk, such as diabetes, weight gain and elevation in LDL-cholesterol. On December 30, 2021 we announced the FDA approval of Recorlev for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative. Recorlev is not approved for the treatment of fungal infections. The approval of Recorlev was based upon safety and efficacy data from two positive Phase 3 studies that evaluated a combined study population of 166 patients, which was representative of the adult drug-treated U.S. population with Cushing’s syndrome. The SONICS study met its primary and key secondary endpoints, significantly reducing and normalizing mean urinary free cortisol concentrations without a dose increase. LOGICS, a double-blind, placebo-controlled randomized-withdrawal study that met its primary and key secondary endpoints, confirmed the efficacy and safety of Recorlev in normalizing and maintaining therapeutic response compared with placebo. Overview of Endogenous Cushing’s Syndrome There are two variants of Cushing’s syndrome: exogenous, which is caused by factors outside the body (e.g., corticosteroid or cortisol-like medications) and endogenous, which is caused by factors within the body. The signs and symptoms may be the same in both forms. The much more common form is exogenous Cushing’s syndrome, which is often found in people taking cortisol-like medications for long periods of time or for shorter periods of time using more potent forms. Cortisol-like medications are often used to treat inflammatory disorders such as asthma and rheumatoid arthritis. Unlike endogenous Cushing’s syndrome, exogenous Cushing’s syndrome may be alleviated by withdrawing the inciting medication. 12
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