BioCryst Pharmaceuticals Backs ORLADEYO Outlook as Navenibart Trial Advances

Key Points

• BioCryst reaffirmed full-year ORLADEYO revenue guidance of $625 million to $645 million and continues to target $1 billion in peak U.S. sales, saying patient demand and reimbursement trends remain supportive.
• The company said its pediatric ORLADEYO launch was delayed by a batch-specific manufacturing issue, but the problem appears isolated and non-safety-related, and early pediatric prescriptions have been ahead of expectations.
• BioCryst’s navenibart Phase 3 trial is nearing completion of enrollment, with top-line six- and 12-month data expected next year and a potential BLA filing by the end of 2027; the company also expects Netherton syndrome data for BCX17725 by year-end.

BioCryst Pharmaceuticals NASDAQ: BCRX CEO Charlie Gayer said the company remains on track with its commercial and development plans during a Jefferies fireside chat, highlighting continued growth expectations for hereditary angioedema drug ORLADEYO, progress for late-stage HAE candidate navenibart and upcoming early data in Netherton syndrome.

Gayer described BioCryst as a rare disease commercialization company led by ORLADEYO, an oral prophylactic therapy for HAE that generated $602 million in revenue last year. He said the drug’s performance reflects both its differentiated oral profile and the company’s patient-focused commercialization approach.

ORLADEYO Guidance Reaffirmed

BioCryst maintained full-year ORLADEYO revenue guidance of $625 million to $645 million after first-quarter revenue of $148.3 million. Gayer said the first quarter was in line with expectations and reflected typical insurance dynamics.

“ORLADEYO’s in the sixth year on the market right now, and we’re at a stage where it’s all about consistent new patient demand,” Gayer said. He added that the company saw more new starts last year than in the first year of launch and ended last year with 82% of patients receiving reimbursement.

Gayer said BioCryst continues to target $1 billion in peak U.S. ORLADEYO sales, excluding Europe and including pediatric sales. To reach that level, he said the company needs to average about 150 net new U.S. patients per year, compared with more than 200 annually over the last several years.

On the market mix, Gayer said a little less than half of ORLADEYO patients have switched from injectable prophylaxis, while just over half have come from new patient starts or patients moving from on-demand treatment to prophylaxis.

He said gross-to-net has historically been in the 15% to 20% range and was closer to 15% last year. BioCryst’s payer mix has remained consistent at about 60% commercial, 20% Medicare Part D and 20% Medicaid, other government programs or uninsured patients.

Pediatric Launch Delayed by Batch Issue

BioCryst’s pediatric ORLADEYO launch was delayed by a batch-specific manufacturing issue. Gayer said the company believes it has identified the root cause and that the issue was isolated to one batch and was not safety-related.

“We’ll be manufacturing again soon,” Gayer said, adding that BioCryst will update customers when product is in pharmacies and ready to ship.

Gayer said early pediatric prescriptions have been ahead of expectations, including prescriptions for all four weight-based strengths of the pediatric pellets. He said the company had been conservative in forecasting the pediatric contribution for the year but now believes it could be on or ahead of plan once product is available.

Navenibart Phase 3 Enrollment Near Completion

BioCryst’s late-stage HAE candidate navenibart is in Phase 3 testing. Gayer said enrollment in the ALPHA-ORBIT trial is on track to finish by the end of June, with the final patients expected to complete the 12-month blinded period by the end of June 2027.

Top-line data for both six- and 12-month results are expected in the third quarter of next year, keeping the company on track to file a biologics license application by the end of 2027, Gayer said. He clarified that a likely launch scenario would be in the latter part of 2028.

Gayer said navenibart is designed as a kallikrein inhibitor with dosing every three or six months. He contrasted that with current injectable prophylaxis options, including Takhzyro, which is dosed every two weeks, and Andembry, which he described as monthly.

In long-term Phase 2 data, Gayer said navenibart showed a 92% reduction from baseline in mean attack rate for three-month dosing and a 90% reduction for six-month dosing. He said the commercial presentation is expected to be a two-milliliter autoinjector, with one injection every three months or two injections every six months.

Gayer said the company sees the largest opportunity among roughly 5,000 U.S. patients already on injectable prophylaxis. He said navenibart has shown essentially no reported injection site pain in Phase 1 and Phase 2 studies, which he attributed to a formulation without citric acid.

Competition in HAE

Gayer said BioCryst assumes a strong competitive profile for Pharvaris’s oral HAE candidate deucrictibant when modeling ORLADEYO’s opportunity. Even under that assumption, he said BioCryst still expects ORLADEYO to reach $1 billion in peak sales because patients doing well on ORLADEYO tend to stay on therapy.

Regarding Intellia’s gene-editing program, Gayer said BioCryst expects interest from some patients but views it as a potential niche option for those who have tried other therapies without success. He also said BioCryst has not seen oral on-demand therapy Ekterly negatively affect ORLADEYO’s trajectory.

Netherton Syndrome Data Expected by Year-End

BioCryst is also developing BCX17725 for Netherton syndrome, a rare skin disorder with no approved targeted therapies. Gayer said the company expects data from 12 patients treated through three months by year-end.

He said a “home run” result would include a consistent effect across patients, meaningful clinical improvement and indications that the company is narrowing in on the right dose. As an example, he said an average improvement of around 40% in a global assessment of skin, combined with consistent patient response, would be encouraging.

Gayer said healthy volunteer data showed BCX17725 reached the epidermis, which he called encouraging. He said it is too early to define a pivotal trial design, though BioCryst’s baseline assumption is that it would prefer a placebo-controlled study.

On business development and financials, Gayer said BioCryst remains open to in-licensing later-stage assets with lower clinical and regulatory risk. He said the company is agnostic on therapeutic area but is unlikely to pursue gene therapy, gene editing or cell therapy.

Gayer said BioCryst had a pro forma cash position of $330 million at the end of the first quarter after licensing navenibart in early second quarter. He said the company was profitable last year, expects to be profitable this year and expects to be more profitable next year.

About BioCryst Pharmaceuticals NASDAQ: BCRX

BioCryst Pharmaceuticals, Inc is a clinical‐stage biotechnology company headquartered in Durham, North Carolina, that focuses on the discovery and development of novel, oral small‐molecule medicines for rare and serious diseases. Since its founding in 1986, the company has leveraged structure‐based drug design to advance a pipeline of targeted therapeutics designed to address underlying disease mechanisms rather than just treat symptoms.

The company's first commercial product, Orladeyo (berotralstat), is an oral kallikrein inhibitor approved for the prophylactic treatment of hereditary angioedema (HAE) in both the United States and Europe.

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