Charlotte’s Milestone Pharmaceuticals advancing heart drug

Milestone Pharmaceuticals, a Canadian company with a U.S. subsidiary in Charlotte, is back on track with a potential drug to treat rapid heart rates in certain cardiovascular disorders.

The company in late March re-submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval of etripamil for the management of paroxysmal supraventricular tachycardia (PSVT), a type of arrhythmia or abnormal heart rhythm. 

“That’s really exciting for us; it gets us back on path,” Joseph Oliveto, Milestone’s president and chief executive officer, said in an interview with the North Carolina Biotechnology Center. “That was a big achievement for our team getting that submitted.”

An NDA was first submitted in October 2023, but the FDA responded with a Refusal to File letter requesting clarification of the timing of reported adverse events in a clinical trial of etripamil.

Based on the agency’s guidance, Milestone’s revised NDA submission includes restructured data sets that capture the timing of reported adverse events and certain data files reformatted to help the FDA’s analyses. No additional efficacy or safety data were requested by the FDA.

With the re-submission, Oliveto said he expected the FDA to render a decision on the drug in about a year from now.
Fast relief for racing hearts

FDA approval would give PSVT sufferers – mostly women – a quick, self-administered treatment for episodes of the disorder, characterized by rapid heart rates, sweating, anxiety, dizziness, fainting, fatigue and chest pain. Current treatments include catheter ablation – an invasive procedure to block electrical signals to the heart – or intravenous drugs, often given during an expensive visit to a hospital emergency room.

Etripamil is a calcium channel blocker, a class of drugs used to reduce the amount of calcium entering the cells of heart muscle and blood vessels. Restricting calcium, an electrolyte involved in sending electrical signals to the heart, is a proven way of treating various arrhythmias.

Etripamil would be administered intranasally by PVST patients with a small pre-filled device about the size of an iPhone, but thicker, Oliveto said. A spray in each nostril – equaling one dose – should slow the rapid heart rates in PSVT within 10 minutes. If not, the device would contain a second dose that should bring relief.

About two million patients in the United States have been diagnosed with PSVT, and 650,000 are treated each year for episodes. The disorder costs about $3 billion in healthcare expenditures annually, according to Milestone.

If FDA approval is granted, Milestone expects to receive a $75 million payment under an existing royalty agreement with shareholder RTW Investments. Proceeds would fund the commercial launch of etripamil spray for PSVT under the conditionally approved brand name Cardamyst.

Milestone also has an exclusive license and collaboration agreement with Ji Xing Pharmaceuticals, a biotechnology company based in Shanghai, to develop and commercialize etripamil for PSVT in China. 

Second indication on horizon

Milestone is also testing etripamil for the treatment of another heart arrhythmia disorder: Atrial fibrillation with rapid ventricular rate, or AFib-RVR.

A recent Phase 2 clinical trial involving 56 AFib-RVR patients generated “really compelling data that etripamil was able to reduce their heart rates,” Oliveto said.

Milestone is now working with the FDA and an advisory team, the electrophysiology group at Duke University School of Medicine, to design a Phase 3 clinical trial that might begin next year, he said.

The market for AFib-RVR is much larger than the PSVT market. 

An estimated five million Americans suffer from AFib, and that number is expected to grow to about 12 million by 2030. A subset of AFib patients have RVR, an abnormally high heart rate.

In 2016, nearly 800,000 patients with AFib symptoms were admitted to an emergency department, where treatment includes intravenous administration of calcium channel blockers or beta blockers, or electrical cardioversion.

With little available data for AFib-RVR, Milestone's initial market research indicates that 30 to 40% of patients with AFib experience one or more symptomatic episodes of RVR per year that require treatment, suggesting a target addressable market of about three to four million patients in 2030 for etripamil in patients with AFib-RVR.

“We think etripamil could help those patients,” Oliveto said.

Charlotte origins

Milestone was founded in 2003 in Montreal, and Oliveto established its U.S. subsidiary in Charlotte in 2017. The company’s stock is traded on the Nasdaq stock exchange under the symbol MIST.

About 10 employees work from Milestone’s Charlotte office, another 10 work in Montreal, and 10 more work in locations throughout the United States.

“We like to call ourselves a small team that punches above our weight,” Oliveto said.

Oliveto took the reins at Milestone after his prior company, Charlotte-based Chelsea Therapeutics, was sold to the Danish global drug company Lundbeck for $658 million.

The Queen City has been a good location for Milestone, he said.

“When we do need to attract someone, Charlotte is a great place to hire into,” he said. “It’s attractive for both younger people as well as more established people because of all that Charlotte has to offer in terms of a big growing city with a lot going on with a good quality of life. The airport’s a huge advantage because we are more virtual now. We get on planes a lot more and need to go see people, so we like having a really strong airport here.”

Oliveto serves on the Greater Charlotte Advisory Committee, a volunteer group that advises NCBiotech on bioscience development in the area.

“We are very fortunate to have Milestone Pharmaceuticals as an engaged partner in the development of our region’s life sciences industry,” said Corie Curtis, executive director of NCBiotech’s Greater Charlotte Office. “The company is not only developing an important product for heart health but is supporting good jobs across the state through its many partnerships with pharmaceutical services companies.”

In particular Milestone is relying on commercial collaborations in the Research Triangle region to advance etripamil. Partners include multiple contract research organizations, a finish manufacturer, a packaging supplier, a consulting firm and a venture capital fund – Pappas Ventures – that supported Milestone before its $95 million initial public offering in 2019.

“Being close to Raleigh and the strength of the Biotech Center and the (Research) Triangle as a hotbed for biotech, that’s an advantage,” Oliveto said.