Biohaven Gets Go-Ahead for Trial of BHV-3241 in Multiple System Atrophy


The novel myeloperoxidase inhibitor was previously licensed by AstraZeneca, but its development has since been taken over by Biohaven, which received IND acceptance from the FDA.

Dr Vlad Coric

Vlad Coric, MD, the chief executive officer of Biohaven

Vlad Coric, MD

The FDA has notified Biohaven Pharmaceuticals that it is clear to proceed with its clinical investigation of BHV-3241, its novel myeloperoxidase (MPO) inhibitor in development for the treatment of multiple system atrophy (MSA).1

Biohaven received the agency’s May Proceed Letter following the reactivation of AstraZeneca’s original Investigational New Drug (IND) application once it acquired the licensing for the treatment in September 2018. It was previously known as AZD3241.

“We are very pleased to report the FDA's acceptance of the IND for BHV-3241 for the treatment of MSA,” Vlad Coric, MD, the chief executive officer of Biohaven said in a statement. “We believe BHV-3241 has the potential to be the first effective treatment for people living with MSA and expect to start our phase 3 trial in the third quarter of 2019."

The first-in-class inhibitor is an oral, brain-penetrant, irreversible inhibitor of the MPO enzyme, intended to relieve the pathological oxidative stress and brain inflammation driven by MPO. It has been investigated in a number of other neurological conditions associated with oxidative stress, inflammation, and neurodegeneration, including Parkinson disease.

While it was in development with AstraZenca, a phase 2 randomized safety and tolerability trial of BHV-3241 was conducted (NCT02388295). The study included 58 patients randomized to a 300-mg twice-daily dose (n = 19), a 600-mg twice-daily dose (n = 20) or placebo (n = 19), and ultimately showed that there were favorable trends on the Unified MSA Rating Scale scores, with less worsening from patients administered the therapy.

At 12 weeks, there was a 3.6-point increase (90% CI, 1.4 to 5.7) for those in the 300-mg group and a 2.6-point increase (90% CI, 0.5 to 4.7) for those in the 600-mg group, compared to a 4.7-point increase (90% CI, 2.5 to 6.8) for those administered placebo.

Additionally, translocator protein (TSPO) positron emission tomography imaging in patients with Parkinson disease demonstrated that BHV-3241 reduces inflammation in disease-relevant regions of the brain. As well, BHV-3241 significantly decreased MPO activity in human blood, a biomarker of the drug engaging its target.2

In total, roughly 250 healthy volunteers were administered the treatment in AstraZeneca’s development program. Irfan Qureshi, MD, the executive director of Neurology at Biohaven commented that the phase 2 trial suggested that BHV-3241 may have reduced MSA disease progression in a dose-dependent manner, measured by the Unified MSA Rating Scale.”

Qureshi noted that "people living with MSA urgently need new therapies. BHV-3241 offers the potential to treat MSA by inhibiting myeloperoxidase enzyme activity, thereby alleviating oxidative stress and neuroinflammation.” He added that BioHaven is “excited to advance into a Phase 3 trial to assess the efficacy of BHV-3241 for the treatment of MSA."

MSA is a rare and rapidly progressive disease which leads to death after an average of 6 to 10 years from disease onset. It results in Parkinson disease-like movement problems such as slow movement, rigid muscles, tremor, and poor balance, along with cerebellar ataxia and problems with autonomic functions, including blood pressure control, bladder function, and digestion. There is no cure for MSA, and currently only symptomatic and palliative therapies are available.


1. Biohaven Receives FDA May Proceed Letter For Phase 3 Clinical Trial Of BHV-3241 For Multiple System Atrophy [press release]. New Haven, CT: Biohaven Pharmaceutical Holding Company; Published January 23, 2019. Accessed January 23, 2019.

2. BHV-3241. Biohaven website. Accessed January 23, 2019.

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