- A key European Medicines Agency committee on Friday recommended approval of a gene therapy developed by PTC Therapeutics to treat a rare neurological disease. The drug, called Upstaza, corrects a mutation that causes AADC deficiency, which disrupts signaling in the nervous system and leads to lifelong disability.
- Approval of PTC's drug comes months after Bluebird bio decided to withdraw two approved gene therapies from Europe in a dispute over reimbursement. If approved by the European Commission, Upstaza would be only one of three gene therapies on the market after Luxturna and Zolgensma, which gained EU approval in 2018 and 2020, respectively.
- AADC deficiency affects an estimated one out of every 118,000 people in the EU, the EMA stated. PTC has identified 300 patients, according to RBC analyst Brian Abrahams, who forecasts $60 million a year in revenue for PTC in Europe.
The recommendation from the EMA's human drugs committee is good news for the gene therapy field after a string of negative developments. Clinical and regulatory setbacks have weighed on company valuations, limiting their fundraising options and leading to restructuring and layoffs for a number of gene therapy developers.
PTC's regulatory decision is the first of several expected in the coming months that, if positive, could help turn investors' views around. After its European disappointment, Bluebird is expecting Food and Drug Administration decisions on its two gene therapies this year, while closely watched projects from BioMarin Pharmaceutical and UniQure could also be under FDA review soon. Likewise, PTC expects by the end of September to ask the FDA for approval of Upstaza.
PTC's therapy corrects a mutation that disrupts production of an enzyme called aromatic L-amino acid decarboxylase, which is in turn vital to production of other chemicals needed for nervous system signaling. As with Luxturna and Zolgensma, Upstaza uses an adeno-associated virus to deliver the corrected gene into cells.
Setting Upstaza apart, however, is that it is infused into the brains of patients using a minimally invasive procedure called stereotactic surgery. Luxturna, for an inherited form of blindness, is injected into the eye, while Zolgensma, which treats a neurological disorder, is an intravenous infusion.
To win support for approval, PTC tested Upstaza in 28 patients between the ages of 18 months and 8 years, 6 months, and compared their development to the documented course of disease for patients with AADC deficiency. Patients treated with the therapy were able to control their heads, sit, stand with support, communicate, and gained cognitive skills that are not normally seen in those with the disorder.
Approvals by the FDA and other regulators in addition to the EMA could help boost PTC, potentially yielding another $200 million in annual revenue, Abrahams wrote in a May 20 note to clients.
PTC already has several products on the market, including the Roche-partnered drug Evrysdi, which competes with Zolgensma, and it holds Latin American and Caribbean marketing rights to Ionis Pharmaceuticals' Waylivra and Tegsedi. The company also sells two treatments for Duchenne muscular dystrophy.
In 2021, PTC earned $539 million in revenue from sales, collaborations and royalties. However, it recorded losses of $524 million due to high research and development as well as general expenses.