Eiger BioPharmaceuticals Announces FDA Approval of Zokinvy™ (lonafarnib): The First Treatment for Hutchinson-Gilford Progeria Syndrome and Processing-Deficient Progeroid Laminopathies
Progeria and Progeroid Laminopathies are separate and distinct ultra-rare, genetic, premature aging diseases that accelerate mortality in young patients. Disease manifestations include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular disease and stroke. Untreated children with Progeria die of heart disease at an average age of 14.5 years. There are 20 children and young adults with Progeria and PL identified and followed in the
Zokinvy is a disease-modifying agent that has demonstrated a statistically significant survival benefit in children and young adults with Progeria. In patients with Progeria, Zokinvy reduced the incidence of mortality by 60% (p=0.0064) and increased average survival time by 2.5 years. The most commonly reported adverse reactions were gastrointestinal (vomiting, diarrhea, nausea), and most were mild or moderate (Grade 1 or 2) in severity. Many Progeria patients have received continuous Zokinvy therapy for more than 10 years.
The increase in survival observed with Zokinvy was derived from two open-label clinical trials (
With this approval, the FDA issued a Rare Pediatric Disease Priority Review Voucher (PRV) to Eiger. The Rare Pediatric Disease Priority Review Voucher program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases. Eiger plans to sell the PRV and under the terms of the Collaboration and Supply Agreement with the
"The FDA approval of Zokinvy is the result of a pioneering partnership between
"The approval of this breakthrough therapy is a critical milestone for the Progeria community and also for Eiger," said
PRF Medical Director,
In support of the patient and healthcare provider community, Eiger is launching our dedicated service center, Eiger OneCare™. This specialized team will offer personalized support, financial assistance, and access to Zokinvy, all designed for Progeria and processing-deficient Progeroid Laminopathy patients. Eiger OneCare™ will be available Monday through Friday from 9 AM to 5 PM Eastern Time at 1-833-MYEIGER (1-833-693-4437).
Eiger will host a conference call
For full prescribing information, visit www.zokinvy.com.
About Zokinvy (lonafarnib)
Zokinvy blocks the accumulation of defective, farnesylated proteins which form tight associations with the nuclear envelope, leading to cellular instability and the process of premature aging in children and young adults with Progeria and processing-deficient Progeroid Laminopathies.
Eiger licensed exclusive worldwide rights to lonafarnib from Merck, known as MSD outside of
About Progeria and Progeroid Laminopathies
Progeria, also known as Hutchinson–Gilford Progeria Syndrome (HGPS), and Progeroid Laminopathies are separate and distinct ultra-rare, fatal, genetic premature aging diseases that accelerate mortality in young patients.
Progeria is caused by a point mutation in the LMNA gene, yielding the farnesylated aberrant protein, progerin. Progeroid Laminopathies are genetic conditions of accelerated aging caused by a constellation of mutations in the LMNA and/or Zmpste24 genes yielding farnesylated proteins that are distinct from progerin. While non–progerin producing, these genetic mutations result in disease manifestations with phenotypes that have overlap with, but are distinct from, Progeria.
Without Zokinvy therapy, children with Progeria die of the same heart disease that affects millions of normally aging adults (arteriosclerosis), but at an average age of 14.5 years. Disease manifestations include severe failure to thrive, scleroderma–like skin, global lipodystrophy, alopecia, joint contractures, skeletal dysplasia, global accelerated atherosclerosis with cardiovascular decline, and debilitating strokes. It is estimated that there are 400 children worldwide with Progeria and 200 children with Progeroid Laminopathies. Of these patients, approximately 180 children and young adults have been identified, including 20 in the
ZOKINVY is indicated in adult and pediatric patients 12 months of age and older with a body surface area (BSA) of 0.39 m2 and above:
- To reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS)
- For the treatment of processing-deficient Progeroid Laminopathies with either:
- Heterozygous LMNA mutation with progerin-like protein accumulation
- Homozygous or compound heterozygous ZMPSTE24 mutations
Limitations of Use
ZOKINVY is not indicated for use in patients with non-HGPS Progeroid Syndromes or with Progeroid Laminopathies known to be processing-proficient. Based upon its mechanism of action, ZOKINVY would not be expected to be effective in these populations.
- Strong or moderate CYP3A inhibitors or inducers
- Lovastatin, simvastatin, and atorvastatin
IMPORTANT SAFETY INFORMATION
- The most common adverse reactions are vomiting (90%), diarrhea (81%), infection (78%), nausea (56%), decreased appetite (53%), fatigue (51%), upper respiratory tract infection (51%), abdominal pain (48%), musculoskeletal pain (48%), electrolyte abnormalities (43%), headache (37%), decreased weight (37%), increased aspartate aminotransferase (35%), myelosuppression (35%), cough (33%), decreased blood bicarbonate (33%), hypertension (29%), and increased alanine aminotransferase (27%).
Gastrointestinal Adverse Reactions
- Gastrointestinal adverse reactions were the most frequently reported adverse reactions. Of the 57 patients (90%) that experienced vomiting, 30 (53%) patients had mild vomiting, 26 (46%) patients had moderate vomiting, and 1 (2%) patient had severe vomiting.
- Of the 35 patients (56%) that experienced nausea, 34 (97%) patients had mild nausea and 1 (3%) patient had moderate nausea.
- Of the 51 patients (81%) that experienced diarrhea, the majority of patients (92%) experienced mild or moderate diarrhea; 38 (75%) patients reported mild diarrhea and 9 (18%) patients reported moderate diarrhea. Four (8%) patients reported severe diarrhea.
- Loss of fluids and dehydration can be severe, leading to hospitalization. As a result, patients should receive therapy for diarrhea at the earliest signs in order to avoid possible severe complications.
Alanine Aminotransferase and Aspartate Aminotransferase Elevations
- Increased alanine aminotransferase was commonly reported (17 [27%] patients). Of the 17 patients with increased alanine aminotransferase, 14 (82%) patients had mild increases, 1 (6%) patient had moderate increases, and 2 (12%) patients had severe increases.
- Increased aspartate aminotransferase was also commonly reported (22 [35%] patients). Of the 22 patients with increased aspartate aminotransferase, 21 (95%) patients had mild increases and 1 (5%) patient had a severe increase.
- Increases in blood pressure have been documented in patients treated with ZOKINVY. At baseline 22 (35%) patients had either a systolic blood pressure or a diastolic blood pressure or both above the 95th percentile. Over the course of the trials, 18 (29%) patients had hypertension based on systolic blood pressure or diastolic blood pressure measurements above the 95th percentile on 3 or more occasions. Five (8%) patients who were normotensive at baseline had either systolic blood pressure or diastolic blood pressure above the 95th percentile at the end of treatment.
Ophthalmic Adverse Reactions
- Lonafarnib caused retinal toxicity in monkeys at 3.7 times the human dose based on plasma drug exposure, but not at 2.1 times the human dose.
Some patients treated with ZOKINVY developed laboratory abnormalities. These included:
- Electrolyte abnormalities (43%), such as hyperkalemia, hypokalemia, hyponatremia, or hypercalcemia
- Myelosuppression (35%), such as reductions in absolute neutrophil count, white blood cell counts, lymphopenia, hemoglobin, or hematocrit
- Increased liver enzymes, such as aspartate aminotransferase (35%), or alanine aminotransferase (27%)
These laboratory abnormalities often improved while continuing ZOKINVY, but it is not possible to exclude ZOKINVY as a cause of the abnormalities. Periodically monitor electrolytes, complete blood counts, and liver enzymes, and manage abnormalities accordingly.
- Lonafarnib caused nephrotoxicity in rats at plasma drug exposures approximately equal to that achieved with the human dose. Monitor renal function at regular intervals during ZOKINVY therapy.
- Lonafarnib caused rod-dependent, low-light vision decline in monkeys at plasma drug exposures similar to that achieved with the human dose. Perform ophthalmological evaluation at regular intervals and at the onset of any new visual changes during ZOKINVY therapy.
- Lonafarnib caused impaired fertility in female rats at 1.2 times the human dose based on plasma drug exposure.
- Lonafarnib caused impaired fertility and testicular toxicity in male rats at 1.5 times the human dose based on plasma drug exposure, and toxicity in the male reproductive tract in monkeys at doses lower than the human dose based on plasma drug exposure.
Eiger is a commercial-stage biopharmaceutical company focused on the development and commercialization of first-in-class, well-characterized drugs for serious rare and ultra-rare diseases for patients with high unmet medical needs.
Zokinvy for the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria) and processing-deficient Progeroid Laminopathies is the Company's first FDA approval. A Marketing Authorization Application (MAA) has been accepted and is under review by the
Eiger's lead clinical programs target Hepatitis Delta Virus (HDV) infection, the most serious form of human viral hepatitis. Eiger is developing two complementary treatments for HDV. Lonafarnib is a first-in-class, oral prenylation inhibitor in a global Phase 3 trial. Peginterferon lambda is a first-in-class, well-tolerated type III interferon entering Phase 3.
For additional information about Eiger and its clinical programs, please visit www.eigerbio.com.
About Rare Pediatric Disease Priority Review Voucher (PRV) Program
Note Regarding Forward-Looking Statements
This press release contains "forward-looking" statements that involve substantial risks and uncertainties. All statements other than statements of historical facts, including statements regarding our future financial condition, timing for and outcomes of clinical results, business strategy and plans and objectives for future operations, are forward-looking statements. These forward-looking statements include terminology such as "believe," "will," "may," "estimate," "continue," "anticipate," "contemplate," "intend," "target," "project," "should," "plan," "expect," "predict," "could," "potentially" or the negative of these terms. Forward-looking statements are our current statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, our anticipating significant milestones in 2020 and 2021, the timing of our ongoing and planned clinical development, including our ability to support the launch of a new product and ship to specialty pharmacies; our development programs for Zokinvy generally; and the potential approval of Zokinvy in jurisdictions outside of the
Investors and Media:
View original content to download multimedia:http://www.prnewswire.com/news-releases/eiger-biopharmaceuticals-announces-fda-approval-of-zokinvy-lonafarnib-the-first-treatment-for-hutchinson-gilford-progeria-syndrome-and-processing-deficient-progeroid-laminopathies-301178343.html