MDGH Update - March 2021

In December 2020, Medicines Development for Global Health (MDGH) announced the licensing of CC-11050 (also known as AMG 634) from Amgen. CC-11050 is a phosphodiesterase type 4 (PDE4) inhibitor being investigated for the treatment of tuberculosis (TB) and erythema nodosum leprosum (ENL), a debilitating inflammatory complication of leprosy. The compound recently completed Phase 2a clinical trials and is about to start Phase 2b studies led by The Aurum Institute NPC (TB study) and The Leprosy Mission Nepal (ENL study). Under the terms of the agreement, MDGH has assumed full responsibility for the further development and commercialization of CC-11050 and has exclusive, worldwide rights for its potential applications in all neglected tropical diseases. Amgen will continue to support the two Phase 2 clinical trials in TB and ENL, set to begin this year, by generously providing CC-11050 to both studies and funding the ENL study. This support will help ensure a seamless transition to development by MDGH.

CC-11050 was originally developed by Celgene (now a Bristol Myers Squibb company) primarily as a back-up for apremilast (Otezla®, which is currently approved for the treatment of psoriasis and psoriatic arthritis). Amgen, one of the world’s leading pharmaceutical companies, acquired CC-11050 and Otezla from Celgene in 2019.‍

Tuberculosis (TB)‍

TB is caused by the bacterium Mycobacterium tuberculosis which usually affects the lungs. However, Mycobacterium tuberculosis can also affect any organ, including the kidney, spine, and brain. As not everyone infected with TB bacteria is symptomatic, TB-related conditions are divided into latent TB infection and TB disease. Nearly a quarter of the world’s population is latently infected with the bacterium that causes TB meaning, they are infected but are not ill. TB disease, however, can be fatal. According to the World Health Organization (WHO), an estimated 10 million people were diagnosed with TB disease, including over 1 million children, and 1.4 million people died of TB in 2019. TB affects the world’s poorest and most vulnerable people, worsening existing inequalities.

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Leprosy

‍Leprosy, also known as Hansen’s disease, affects the skin, peripheral nerves and mucosal surfaces of the upper respiratory tract and the eyes. Leprosy affects poor and marginalized populations in low- and middle-income countries. According to the WHO, over 200,000 new leprosy cases were registered in 2018 across 127 countries, with the largest number of cases in India, followed by Indonesia and Brazil.

Between 30 and 50% of people with leprosy will go on to have ENL, a Type 2 inflammatory syndrome characterised by painful erythematous cutaneous nodules, neuritis and fever. ENL is often characterised by chronicity and recurrence commonly resulting in permanent nerve damage and disability. While leprosy is curable with multidrug therapy, ENL can occur before, during or even years after successful completion of multidrug therapy: in other words, ENL is a lifelong risk of leprosy that can occur long after the infection is cured.

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Corticosteroids are the mainstay of treatment of ENL but long-term usage of steroids poses the risk of adverse effects and dependency: several serious adverse effects of corticosteroids are both dose and time-dependent. Thalidomide, as a representative of the PDE4 inhibitor class, is highly effective in the treatment of ENL but it is not used due to the well-documented risk in pregnancy. CC-11050 represents a new treatment for a poorly managed disease with very limited well tolerated/low risk treatment options.

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Our plans

MDGH will embark on full development of CC-11050 for both indications, working in collaboration with the Leprosy Mission and the Aurum Institute on the next phase of clinical trials while generating the data required for the regulatory dossier. MDGH intends to seek stringent regulatory authority approval through the United States Food and Drug Administration (FDA), noting that CC-11050 may also be eligible for a Priority Review Voucher (PRV).

MDGH acknowledges the generosity of Amgen to make it possible for MDGH to take on this program. Dr. Vikram Khetani, formerly an Executive Director for product development and the project leader for CC-11050 at Celgene, is also joining MDGH to provide the project leadership of the program. Dr Khetani’s expertise and history with CC-11050 will be invaluable for ensuring the seamless development of this compound at MDGH. Amongst the earliest expenditure for the program will be the US$30,000 to secure a name for CC-11050/AMG634.