The transthyretin amyloidosis (ATTR) market is expected to grow from $585m in 2019 to $14.1bn in 2029 across the seven major markets (7MM*) at an impressive compound annual growth rate (CAGR) of 37.5%, according to GlobalData, a leading data and analytics company.

The company’s latest report, ‘Transthyretin Amyloidosis: Global Drug Forecast and Market Analysis to 2029’, states that growth will be driven by the surge in development of drug therapies of varying mechanisms, and the overall rise in diagnosed patient population due to a much-needed increase in awareness and understanding of the disease among clinicians and the public.

Until recent years, there have been minimal therapeutic options for ATTR, in both ATTR cardiomyopathy and ATTR polyneuropathy sub-populations, with only one approved therapy or off-label generics. Key opinion leaders (KOLs) have cited this as the cause for no incentive for diagnosis. Further to this, the lack of awareness surrounding the disease led to many misdiagnoses and long delays in diagnosis. The pipeline agents entering the market over the next ten years will greatly increase diagnosis rates and enable more choice for prescribers.

The 7MM vary in market profiles as the Food and Drug Administration (FDA) did not approve the first developed therapy for ATTR polyneuropathy, Pfizer’s Vyndaqel (tafamidis), meaning sales for the drug relied on the rest of the 7MM. Since the FDA granted the drug approval status in 2018 alongside its approval in the 5EU and Japan for a label expansion in ATTR cardiomyopathy, it is beginning to take a larger market share.

New mechanisms have also entered or are entering the market in the form of RNA interference (RNAi) therapies that aim to block production of TTR at the source. This novel mechanism is giving Alnylam’s Onpattro (patisiran) a huge boost in market share and the trend is set to continue for its second drug vutrisiran, AKCEA’s Tegsedi (inotersen) and AKCEA-TTR-LRx, all of which will compete for market share within the RNAi class.

Heather Farrell, Pharma Analyst at GlobalData, comments: “The influx of pipeline therapies in the ATTR market brings a surge in growth the market has never seen before, meaning that patients will be treated with a choice of approved therapies. The mechanisms of each new class of drug entering the market are varied and so the potential for a new combination strategy within the landscape is highly likely, and something that could really benefit patients while also providing a lucrative venture for drug developers.”

The ATTR market is expected to start to lean towards use of RNAi therapeutics compared to the oral TTR stabilizers such as Vyndaqel or off-label diflunisal. Onpattro is expected to become a market leader as the drug gains increasing support from KOLs and will pave the way for RNAi therapeutics to lead the market. However, there will be fierce competition as new therapies and mechanisms enter the market such as the amyloid clearance drugs, Prothena’s PRX004 and Proclara’s NPT189, that are in early development stages. These therapies are hoped to meet the huge unmet need of therapy for advanced stage ATTR, which makes up the majority of diagnosed cases.

Farrell added: “Although many unmet needs will be fulfilled in the upcoming years, there are still important areas that remain in need of resolution. Advanced stage ATTR therapies are key to the future of the disease and will become large players in the market, especially if combination strategies are explored.”

Increased awareness will also be a game-changer within the ATTR market as many KOLs believe the disease is entirely underdiagnosed and misdiagnosed. What was once perceived as a rare disease may affect more patients than fully realised. The market itself is therefore a huge opportunity for drug developers as it continues to grow. Farrell concluded: “The ATTR market is currently has unlimited competition and holds room for new entrants, especially those that meet unmet needs or prove to be efficaciously superior. Drug developers would benefit from investing in genetic testing schemes to uncover the depth of disease prevalence and increase their patient pool further.”

*7MM: US, 5EU (France, Germany, Italy, Spain and the UK) and Japan