rare diseases Archives - The Antibody Society

Rare Disease Day is held to raise awareness of the more than 7,000 diseases that each affect a small number of people. In the US, any disease affecting fewer than 200,000 people (1 per ~1,650 people) is considered rare, while in Europe rare diseases ae defined as those that affect fewer than 1 in 2,000 people.

Regulatory agencies in the US, Europe, Japan, as well as other countries, have ‘orphan drug’ programs, which incentivize the development of drugs to treat rare diseases. Numerous monoclonal antibody (mAb) therapeutics have been granted Orphan Drug designations, as illustrated by the examples below.

Recently approved by FDA

Tebentafusp (KIMMTRAK®) for uveal melanoma

Approved by FDA in January 2022, tebentafusp-tebn is a bispecific fusion protein composed of: 1) a T cell receptor (TCR) recognizing a human leukocyte antigen (HLA)-A*02:01 complexed with a peptide derived from gp100 antigen expressed by melanoma cells, and 2) an antibody single-chain variable fragment that binds CD3 present on T cells. Developed by Immunocore, this molecule creates a bridge between tumor cells and immune cells, and thus facilitates tumor-cell killing by T cells. As the TCR domain recognizes a peptide presented on HLA-A*02:01, tebentafusp can only be used to treated patients expressing this HLA type. Tebentafusp was granted Breakthrough Therapy, Fast Track, and Orphan Drug designations by the FDA. Tebentafusp is marketed by Immunocore Holdings plc.

Sutimlimab (Enjaymo) for cold agglutinin disease

Sutimlimab-jome, a hinge-stabilized, humanized IgG4k antibody that targets and inhibits complement component 1s (C1s), was approved by FDA in February 2022 as a treatment of hemolysis in adult patients with cold agglutinin disease (CAD). A mutation in the Fc region (L235E) reduces the effector functions of the antibody. This rare autoimmune disorder is characterized by hemolysis caused by activation of the classic complement pathway. Sutimlimab received FDA’s Breakthrough Therapy and Orphan Drug designations for CAD, and Orphan Drug designation in the European Union for this indication. Sutimlimab is marketed by Sanofi.

Biological license applications in FDA review

Spesolimab (Boehringer Ingelheim) for generalized pustular psoriasis

Spesolimab is a humanized IgG1k antibody that blocks activation of the IL-36 receptor, which is involved in the pathogeneses of neutrophilic skin diseases such as generalized pustular psoriasis (GPP), palmoplantar pustulosis and hidradenitis suppurativa. FDA granted spesolimab Orphan Drug designation for the treatment of GPP. Marketing applications are undergoing evaluation by the FDA, as well as the European Medicines Agency (EMA).

Teclistamab (Janssen Research & Development, LLC) for multiple myeloma

Teclistamab (JNJ-64007957) is an IgG4l T-cell redirecting antibody derived from Ligand’s transgenic mouse (OmniAb) and Genmab’s DuoBody technology. The antibody selectively targets BCMA and CD3. Teclistamab was granted Breakthrough Therapy designation for the treatment of relapsed or refractory multiple myeloma (MM) by the FDA, and EMA’s PRIME designation for treatment of adult patients with relapsed or refractory MM who previously received ≥3 prior lines of therapy in 2021. Teclistamab had previously been granted Orphan Drug designations for MM in both the US and EU. Marketing applications are undergoing evaluation by the FDA and EMA.

BLA submission anticipated in Q1 2022

Mirvetuximab soravtansine (ImmunoGen, Inc.) for ovarian cancer

Mirvetuximab soravtansine (IMGN853), comprising a humanized folate receptor alpha (FRα) IgG1k antibody conjugated to the maytansinoid drug DM4 via a cleavable disulfide linker, is being developed by ImmunoGen as a treatment for epithelial malignancies, including ovarian cancer adenocarcinoma. The drug has been granted US and EU Orphan Drug designations for ovarian cancer, as well as FDA’s Fast Track designation for a specific subset of patients with medium to high FRα-positive platinum-resistant ovarian cancer who received at least one, but no more than three prior systemic treatment regimens, and for whom single-agent chemotherapy is appropriate as the next line of therapy. ImmunoGen anticipates submission of a biologics license application in the first quarter of 2022, with potential accelerated approval in 2022.

Keep up to date on the late-stage pipeline and antibody therapeutic approvals all year by visiting our website!

More information about approved antibody therapeutics, including target, format and year of approval, can be found here.

More information about antibody therapeutics in late-stage studies can be found in ‘Antibodies to Watch in 2022‘ and in our searchable online table found here.

On or about the last day of February each year, the rare disease community comes together to raise awareness of these conditions. In the US, any disease affecting fewer than 200,000 people (1 per ~1,650 people) is considered rare, while a disease is defined as rare in Europe when it affects fewer than 1 in 2,000 people. There are more than 7,000 rare diseases, and these collectively affect ~ 25-30 million Americans. Information about specific rare diseases can be found in the National Organization for Rare Disorders’ Rare Disorders Database and the National Institutes of Health’s Genetic and Rare Diseases Information Center.

In the US, the Orphan Drug Act passed by Congress in 1983 incentivizes the development of drugs to treat rare diseases. Similar programs in Europe, Japan, as well as other countries, also allow other regulatory agencies to grant ‘orphan drug’ designations. Hundreds of drugs have been approved for the treatment of rare diseases, including numerous antibody therapeutics, although substantial medical need still remains. Antibody therapeutics recently approved for rare diseases include:

Caplacizumab (Cablivi), a treatment for acquired thrombotic thrombocytopenic purpura, which is a rare blood clotting disorder.
Crizanlizumab (Adakveo), indicated to reduce the frequency of vaso-occlusive crisis, which is a painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells.
Teprotumumab (Tepezza), indicated for thyroid eye disease, which is associated with an outward bulging of the eye that can cause eye pain, double vision, light sensitivity or difficulty closing the eye.
Inebilizumab (Uplizna) and satralizumab (Enspryng), treatments for neuromyelitis optica spectrum disorder, which is a rare autoimmune disorder of the central nervous system that primarily damages the optic nerve(s) and spinal cord, causing blindness, muscle weakness and paralysis.
Evinacumab (Evkeeza), a treatment for homozygous familial hypercholesterolemia, which is a genetic condition that causes severely high cholesterol.
Ansuvimab (Ebanga) and the triple antibody cocktail of atoltivimab, maftivimab, and odesivimab (Inmazeb) for the treatment for Zaire ebolavirus (Ebolavirus) infection.
Naxitamab (DANYELZA®) for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow.

More information about these antibody therapeutics, including target, format and year of approval, can be found here.

Other antibody therapeutics for rare diseases are in late-stage clinical studies and may be approved soon, including:

Garetosmab, which is undergoing evaluation as a treatment for fibrodysplasia ossificans progressive (FOP), an ultra-rare genetic disorder characterized by the progressive replacement of soft tissue, such as muscles, tendons, and ligaments, by bone, a process known as heterotopic ossification. Regeneron plans regulatory submission(s) for garetosmab for FOP in 2021.
Mirvetuximab soravtansine, which is undergoing evaluation as a treatment for ovarian cancer. ImmunoGen anticipates the submission of a biologics license application for accelerated approval of mirvetuximab soravtansine for ovarian cancer during the second half of 2021.
KN046, which is undergoing evaluation as a treatment for thymic carcinoma. Alphamab Oncology has announced that the Phase 2 clinical trial (NCT04469725) of KN046 to treat thymic carcinoma will support their plan to submit marketing applications for KN046 to China’s National Medical Products Administration and the US Food and Drug Administration in 2021.

More information about antibody therapeutics in late-stage studies can be found in ‘Antibodies to Watch in 2021‘.

Keep up to date on US and EU approvals all year by visiting our website!

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Rare Disease Day, February 28, 2022