LONDON – It was third time lucky for Acacia Pharma Group plc, as the FDA finally gave approval to Barhemsys (amisulpride) as a rescue treatment for surgical patients suffering postoperative nausea and vomiting (PONV), despite standard-of-care treatment.

The product becomes the first antiemetic to be approved for second-line treatment, opening up a U.S. market of an estimated 16 million patients per annum who experience PONV even though they have received standard prophylaxis.

In addition, the label will allow Barhemsys to be used in combination with an antiemetic of a different class, to treat PONV in high-risk patients.

According to health economic data accumulated during clinical development, hospitals will see savings of an average of $670 per patient, through reduced time in post-anesthesia care units and earlier discharge from hospital.

“The approval of our first product represents a significant milestone in Acacia’s evolution into an integrated hospital pharmaceutical company,” said Mike Bolinder, CEO. “This is transformational for us, and we think there is a large and concentrated market out there for the Barhemsys,” he told BioWorld.

FDA previously declined to approve Barhemsys in October 2018 and May 2019, on the grounds it was not happy with the quality standards at Acacia’s chosen API manufacturer.

That has given the Cambridge, U.K.-based company plenty of time to prepare the ground, and Bolinder said early commercialization efforts will begin immediately, with a view to a full launch taking place midyear. He said it expects it to take a year to get signed on by hospital formularies and for sales to ramp up.

Although amisulpride, a dopamine D2/D3 antagonist, has been approved for more than 25 years in Europe as an oral antipsychotic, it has never been registered in the U.S. The intravenously administered low-dose formulation of Barhemsys has U.S. patent protection running to 2031, but to be commercially successful will have to eat into a market that is largely dominated by low-cost generics.

“Of 49 million surgical patients who get antiemetics, 16 million still get PONV and will need rescue treatment. This area of greatest unmet need is where we will place our effort at launch,” said Bolinder. “Actually, we are not competing against generics; we want [Barhemsys] to be used on top of standard of care.”

Patients are assessed pre-surgery for risk of PONV, but the causes of nausea and vomiting are complex and multifactorial, and approved antiemetics only achieve a 30% risk reduction. As a result, patients may need multiple treatments. Currently, most are treated with 5-HT3 receptor antagonists, and according to Acacia, 69% of those who fail to respond receive repeat administration of a 5-HT3 antagonist. That is despite this being against guidelines, which say patients should be treated with a different class of antiemetic.

“When asked why they are doing it, they say, ‘What am I supposed to do? I have a patient who is actively sick’,” Bolinder said.

As another alternative, about 20% of rescue patients receive steroids, which Bolinder noted, are slow to take effect.

It may be self-serving, but Acacia’s market research indicates patients facing surgery worry more about PONV than postoperative pain. With no product approved for rescue therapy, clinicians have told the company, “if a drug was available, we would use it in the vast majority [of these patients],” Bolinder said.

He added that key opinion leaders in the field are in the process of updating the guidelines for PONV and have approached Acacia for details of Barhemsys. “They intend to publish them in the coming months. We haven’t seen them, but believe they will be favorable because we are the only new entrant,” said Bolinder.

Acacia has set up a U.S hospital-focused sales and marketing operation based in Indianapolis and is hiring a sales force in anticipation of the launch. There also is some further work in terms of supply chain and stocking, but Bolinder said he is now confident of the quality of the API, and the company has put FDA concerns about the contract manufacturing behind it.

Barhemsys has a long shelf-life and does not require refrigeration, allowing Acacia to build up stocks in advance of the launch.

To capitalize on the approval and support the launch, Acacia is now looking to raise further funding, either in a placing or through a loan. In addition, it owns 100% of the rights to Barhemsys, and will be opening formal negotiations on licenses in other markets. The clinical development program took place partly in Europe and Bolinder said the existing file will be sufficient to submit a marketing application to the EMA.

Shares in Acacia, which is quoted on Euronext Brussels [EBR:ACPH] rose by 15% to close at €3.22 (US$3.54) when the news was announced on Feb. 27.