Orladeyo’s FDA approval Heralds New Funding for BioCryst

On December 3rd, BioCryst Pharmaceuticals announced that the Food and Drug Administration (FDA) approved Orladeyo (Berotralstat) as a preventative treatment for attacks of hereditary angioedema (HAE) in adult and pediatric patients. Orladeyo is the first approved therapy to be taken orally once a day to prevent attacks of angioedema. It presents an attractive alternative to current prophylaxis therapies that need to be injected.

Soon after, on December 6th, the company announced that Royalty Pharma plc and Athyrium Capital Management, LP, have decided to provide total funding of US$ 325 million to support the launch of Orladeyo in HAE and the development of its oral Factor D inhibitor, BCX9930.

Hereditary Angioedema

Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent episodes of rapid swelling of the extremities, limbs, intestinal tract, and airways. The swelling can lead to debilitating pain and can be life-threatening. HAE is caused by a genetic mutation that results in the lack of or impaired function of the C1-inhibitor protein. This protein is an upstream regulator of vascular permeability, and without it, there is a build-up of fluids leading to swelling.

Worldwide, there are between 50,000 to 150,000 people living with HAE. Additionally, if a parent has HAE, it has a 50% chance of passing it down to their kids. Currently, there are three treatments used to reduce the number of HAE attacks, Cinryze, Lanadelumab, and Haegarda; however, all of these are administered via subcutaneous injection. New and less invasive therapies are necessary.

Orladeyo for the Treatment of HAE

Orladeyo prevents HAE attacks by inhibiting the protein plasma kallikrein. High levels of this protein can lead to swelling in HAE patients. Plasma kallikrein is normally regulated by C1-inhibitor protein; however, patients with HAE lack or have a defective version of this protein. In the APeX-2 trial, a placebo-controlled phase 3 clinical trial to determine the safety and efficacy of Orladeyo, once a day oral administration of 150 mg of the drug had no major side effect. Most importantly, Orladeyo was able to reduce the average number of attacks from 2.9 attacks per month to 1.0 attacks per month after 48 weeks of treatment. Additionally, patients reported an improvement in the quality of life and overall satisfaction.

“Orladeyo offers people with HAE and their physicians the first orally administered non-steroidal option for preventing HAE attacks and represents an important and a welcome step in making more treatment options available to physicians and patients,” said Anthony J. Castaldo, President and Chief Executive Officer of the US Hereditary Angioedema Association (HAEA).

Currently, there are two ongoing clinical trials for Orladeyo. The APeX-S is an ongoing Phase 2/3 multicenter trial to evaluate the long-term efficacy and safety of this treatment, while APeX-J is a placebo-controlled Phase 3 clinical taking place in Japan.

Funding Terms and Upcoming Competition

According to the funding agreement, Royalty Pharma will make an upfront cash payment of US$ 125 million to BioCryst. In return, it will receive royalties on the direct annual net sales of Orladeyo to the effect of 8.75% on sales of up to US$ 350 million, 2.75% on sales between US$ 350 million and $550 million, no royalty on sales over US$ 550 million. In addition, it will also receive a tiered percentage of sublicense revenue in certain territories and a 1% royalty on the global net sales of BCX9930 if it is approved.

Similarly, Athyrium Capital Management will provide BioCryst with a US$ 200 million credit facility, of which US$ 125 million would be available at closing. Additional capital is available if revenue milestones are met.

“The substantial financial commitment of exceptional long-term partners like Royalty Pharma and Athyrium Capital Management enables BioCryst to fully invest in the launch of Orladeyo and to accelerate the development of BCX9930 to address an unmet need for patients and deliver value to shareholders. We believe today’s financing reflects the next step in the transformation of BioCryst,” said Jon Stonehouse, Chief Executive Officer of BioCryst.

Orladeyo is the first FDA approved oral prophylaxis treatment for adults and children over 12 with HAE. However, there is another oral inhibitor of plasma kallikrein currently in Phase 2 clinical trials and one scheduled to begin Phase 2 trials in 2021. KVD900 was developed as a treatment for HAE attacks, while KVD824 is being tested as a preventative treatment for HAE attacks. If successful, KVD824 would directly compete with Orladeyo. Both treatments were developed by KalVista Pharmaceuticals. It is worth noting that, Intellia’s NTLA-2002, an investigational gene-editing therapy for treating HAE, is currently in preclinical trials.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: Genentech Enters Spinal Muscular Atrophy Market with Risdiplam’s FDA Approval

References

1. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-fda-approval-orladeyotm-berotralstat-first
2. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-325-million-funding-royalty-pharma-and
3. https://rarediseases.org/rare-diseases/hereditary-angioedema/
4. https://www.gov.uk/government/publications/berotralstat-in-the-treatment-of-hereditary-angioedema/berotralstat-treatment-protocol-information-for-healthcare-professionals
5. https://angioedemanews.com/bcx7353-berotralstat/
6. https://www.kalvista.com/products-pipeline

Author

Daniel Ojeda