Lonafarnib, sold under the brand name Zokinvy, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used to reduce the risk of death due to

Hutchinson-Gilford progeria syndrome Progeria is a specific type of progeroid syndrome, also known as Hutchinson–Gilford syndrome or Hutchinson–Gilford progeroid syndrome (HGPS). A single gene mutation is responsible for causing progeria. The affected gene, known as lamin A (' ...

and for the treatment of certain processing-deficient progeroid

laminopathies Laminopathies ('' lamino-'' + '' -pathy'') are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. Since the first reports of laminopathies in the late 1990s, increased research efforts have sta ...

in people one year of age and older. It is under trial for its use as combination treatment for Hepatitis D Virus. The most common side effects included nausea, vomiting, headache, diarrhea, infection, decreased appetite and fatigue. Lonafarnib was approved for medical use in the United States in November 2020, and in the European Union in July 2022. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

Medical uses

Lonafarnib is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

to be used to reduce the risk of death due to

and for the treatment of certain other processing-deficient progeroid

in people one year of age and older. Ongoing studies and clinical trials have found a correlation of lonafarnib treatment with cure of hepatitis D (HDV). Up to now, the trials have proven an efficacy of lonafarnib on HDV if combined with ritonavir, as a supportive treatment for pegylated interferon alpha therapy.

Contraindications

Lonafarnib is contraindicated for co-administration with strong or moderate CYP3A inhibitors and inducers, as well as midazolam and certain cholesterol-lowering medications.

History

Lonafarnib, a farnesyltransferase inhibitor, is an oral medication that helps prevent the buildup of defective

progerin Progerin (UniProt# P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a sporadic single point nucleotide polymorphism c.1824 C>T (GGC -> ...

or progerin-like protein. The effectiveness of lonafarnib for the treatment of Hutchinson-Gilford progeria syndrome was demonstrated in 62 patients from two single-arm trials (Trial 1/NCT00425607 and Trial 2/NCT00916747) that were compared to matched, untreated patients from a separate natural history study. Compared to untreated patients, the lifespan of Hutchinson-Gilford progeria syndrome patients treated with lonafarnib increased by an average of three months through the first three years of treatment and by an average of 2.5 years through the maximum follow-up time of 11 years. Lonafarnib's approval for the treatment of certain processing-deficient progeroid laminopathies that are very rare took into account similarities in the underlying genetic mechanism of disease and other available data. The participants were from 34 countries around the world, including the United States. The U.S.

(FDA) granted the application for lonafarnib

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

, and

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...

designations. In addition, the manufacturer received a rare pediatric disease priority review voucher. The FDA granted the approval of Zokinvy to Eiger BioPharmaceuticals, Inc.

Society and culture

Legal status

On 19 May 2022, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Zokinvy, intended for the treatment of patients with progeroid syndromes. The applicant for this medicinal product is EigerBio Europe Limited. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. It was approved for medical use in the European Union in July 2022.

Research

Lonafarnib is a

farnesyltransferase inhibitor The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras (protein), which is commonly abnormally active in ...

(FTI) that has been investigated in a human clinical trial as a treatment for

progeria Progeria is a specific type of progeroid syndrome, also known as Hutchinson–Gilford syndrome or Hutchinson–Gilford progeroid syndrome (HGPS). A single gene mutation is responsible for causing progeria. The affected gene, known as lamin A ( ...

, which is an extremely rare

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...

in which symptoms resembling aspects of

aging Ageing (or aging in American English) is the process of becoming Old age, older until death. The term refers mainly to humans, many other animals, and fungi; whereas for example, bacteria, perennial plants and some simple animals are potentiall ...

are manifested at a very early age. Lonafarnib is a synthetic

tricyclic Tricyclics are cyclic chemical compounds that contain three fused rings of atoms. Many compounds have a tricyclic structure, but in pharmacology, the term has traditionally been reserved to describe heterocyclic drugs. They include antidepr ...

halogenated In chemistry, halogenation is a chemical reaction which introduces one or more halogens into a chemical compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, drugs ...

carboxamide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms. The amide group is called a pe ...

with antineoplastic properties. As such, it is used primarily for cancer treatment. For those with progeria, research has shown that the drug reduces the prevalence of stroke and transient ischemic attack, and the prevalence and frequency of headaches while taking the medication. A phase II clinical trial was completed in 2012, which showed that a cocktail of drugs that included lonafarnib and two other drugs met clinical efficacy endpoints that improved the height and diminished the rigidity of the bones of progeria patients.

References

External links

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"Experimental Drug Is First To Help Kids With Premature-Aging Disease"

NPR National Public Radio (NPR) is an American public broadcasting organization headquartered in Washington, D.C., with its NPR West headquarters in Culver City, California. It serves as a national Radio syndication, syndicator to a network of more ...

, 24 September 2012 * * {{Portal bar , Medicine Benzocycloheptapyridines Chloroarenes Farnesyltransferase inhibitors Bromoarenes Orphan drugs Piperidines Ureas