In a statement, the body said the drug has been considered unjustifiably expensive and not sufficiently cost effective
The HSE is reportedly not recommending the reimbursement of cystic fibrosis Orkambi.
In a statement, the HSE said they had undertaken "considerable engagement and negotiation" with the manufacturer of the drug Vertex in an effort to secure a price reduction.
Both the National Centre for Pharmacoeconomics (NCPE) and the HSE Drugs Committee found the drug to be "unjustifiably expensive and not sufficiently cost effective".
Orkambi costs the HSE €159,000 per patient annually. The HSE said the drug did not provide enough benefits to justify the price.
The Sunday Business Post initially reported the rejection.
In a statement, Cystic Fibrosis Ireland expressed its "dismay and its opposition" to the development.
"We will fight this decision and we call on the Minister for Health, Simon Harris TD, to use his Ministerial powers to intervene to ensure that Orkambi is made available in Ireland for the 550 patients who stand to benefit from this life-lengthening drug," the organisation said.
"Cystic Fibrosis Ireland is angry at the cynical way the HSE has conveyed this information to our patients, some of whom are very ill. The decision was leaked to a Sunday newspaper even before the Minister was informed, never mind patients. It’s a disgraceful and heartless form of communication."
On foot of the story, Mr Harris has written to the head of Cystic Fibrosis Ireland Philip Watt, saying he does not see this as the end of the process and stressed that "the HSE has not concluded their assessment process".
"I am both annoyed and upset that details seemed to leak regarding these discussions today", he wrote. "I have not yet received a decision from the HSE Directorate regarding Orkambi. The HSE is responsible for the assessment of new medicines, as you know, which is a statutory process.
"I am frustrated that this seems to have been extraordinarily difficult. I understand that the HSE has engaged extensively with the company and has sought a significant price reduction. I fully support the HSE in its attempts to lower the exorbitant price the company is seeking to charge for Orkambi for Irish patients.
"My Department can only consider requests for funding requirement for a new drug if the HSE decides to reimburse the drug but does not have the resources to fund the medicine," he stressed.
Speaking on The Sunday Show, Orkambi user Brian O'Carroll questioned how effective the drug had to be. Mr O'Carroll took part in a two-year trial of the drug funded by Vertex.
"I'm doing so well. I haven't been sick for three years. I don't know what improvement they want to see", he said. "If they could see me, and how well I look, the drug would be funded tomorrow.
Cystic fibrosis sufferer Jillian McNulty said she met with Minister for Health Simon Harris two weeks ago to discuss the ongoing talks, with the Minister saying that it was a clinical and medical decision.
"I am devastated - and very frightened", she said. "Orkambi has transformed my life. I couldn't drive myself before Orkambi. I'm a lot stronger.
"It's morally wrong. They [the HSE] need to see the difference it can make."