Mavacamten

Mechanism of Action

Myosin is a family of enzymes that can produce mechanical output by an ATP-mediated cyclic interaction with actin. When ATP is bound to the myosin head, it is hydrolyzed into ADP and organophosphate by myosin ATPase activity, and the energy produced from the reaction is stored in the myosin head. As the organophosphate dissociates from myosin, it shifts myosin into a strong binding state to actin, thus creating a myosin-actin complex otherwise known as "cross-bridging".2,3,5Dissociation of the organophosphate also causes a conformation change in myosin that creates strain in the actin-myosin bridge that can only be released once the actin and myosin filaments slide past each other, thus shortening the sarcomere and create a muscle contraction.5,9 Once the sliding is completed, ADP is released to create further movement of the myosin head.9 Although this ADP release-induced movement is minor and unlikely to contribute to the sarcomere movement, researchers have hypothesized that this movement is likely essential in limiting the sliding velocity of actin.6,7,8,9Finally, myosin then bind to a new ATP molecule to initiate the chemomechanical cycle again.

Mavacamten reduces sarcomere hypercontractility by acting as an allosteric and reversible modulator of the beta-cardiac isoform of myosin to reduce its ATPase activity, thus reducing actin-myosin cross bridging.4 Specifically, mavacamten inhibits the phosphate release, the cycle's rate-limiting step, without affecting the ADP release rate in actin-bound myosin.1Also, mavacamten inhibits binding of ADP-bound myosin to actin as well as ADP release to prime the myosin head to initiate turnover.3Recently, it was also discovered when myosin is not in its active state to interact with actin, it exists in equilibrium between 2 energy sparing states: a disordered relaxed state, where interaction between actin and myosin by the thin filament regulatory proteins, and a super relaxed state, where significant myosin head-to-head interaction lengthen ATP turnover rate.10,11. Mavacamten's binding to myosin can shift the equilibrium toward the super relaxed state, effectively exerting both a basal and actin-activated ATP inhibition

Indication

Mavacamten is indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms

Dr. Reddy's Expertise

Headquartered in Hyderabad, India, Dr. Reddy's Laboratories is one of the leading Active Pharmaceutical Ingredients (API) manufacturers and suppliers globally for Mavacamten API. Dr. Reddy's API business is a preferred partner to pharma companies across the US, Europe, Brazil, Latin America, Japan, China, Korea, Middle East and other emerging markets.

Dr. Reddy's API business thrives on the deep technical strengths established over the last 30+ years in the development and manufacture of complex APIs such as steroids, peptides, complex long chain molecules and highly potent APIs (HPAPIs / oncology drugs). This expertise is complemented by our prowess in intellectual property and regulatory affairs which helps us consistently meet and exceed regulatory standards. Dr. Reddy's Mavacamten API is the outcome of the extensive expertise in R&D, IP, and Regulatory.

A key component in helping our customers be first to market is a responsive supply chain. We achieve this by making sure that all our facilities are operating efficiently and to the latest standards of quality, safety, and productivity. A strong interconnect between business and factories allows for a quick reaction to dynamic market changes, so that we can avert shortages and meet sudden surges in demand.