Shire Continues To Grow HAE Franchise With Takhzyro, As Hemophilia Takes A Hit

Approved in late August, the HAE prophylaxis drug has already yielded $51m in US revenues, with EU approval expected by year-end. The HAE franchise is a growth leader for Shire, despite peaks and valleys due to supply issues.

Due to Shire PLC’s pending merger with Takeda Pharmaceutical Co. Ltd. – which is on track to close in the first half of 2019 – its recent quarterly earnings calls have become subdued affairs, with company execs quickly putting off-limits some of the topics analysts might be most curious about. But during Shire’s third quarter investor call Nov. 1, the Dublin-based firm pointed to early launch optimism for its new hereditary angioedema (HAE) drug Takhzyro in the US and said the prophylactic could catalyze overall growth of the HAE franchise.

CEO Flemming Ornskov cautioned at the beginning of the call, as he did during the second quarter call in July, that Shire executives cannot say much about the ongoing merger with Takeda. (Also see "Takeda Grabs Shire At Last After Long Pursuit" - Scrip, 8 May, 2018.) Integration is ongoing, he said, and the Japanese pharma has received regulatory clearances in the US, Japan and China, while it works toward clearance in Europe.

On Nov. 1, Takeda substantially increased its current year revenue forecasts, with prospects from the Shire merger cited as one of the reasons why. (Also see "Takeda Bumps Forecast On 'Significant Momentum' Pre-Shire" - Scrip, 1 Nov, 2018.)

Ornskov reported that Shire posted 6% year-over-year sales growth to a total of $3.75bn for the quarter, with the four-drug HAE franchise up 23% to $329m, including US sales of $291.3m. (Also see "Immunology Leads Shire's 2017 Sales Growth With Addition Of HAE Portfolio" - Scrip, 14 Feb, 2018.) In all, the immunology sector – comprising HAE, immunoglobulin therapies and biotherapeutics – posted 12% growth to just under $1.2bn.

Shire’s immunoglobulins for rare immunological and neurological diseases – Cuvitru, GammaGard and Hyqyvia – totaled $656m for the quarter, up 8%. During the second quarter, those three products yielded 20% growth. Ornskov noted that on Oct. 25 Shire filed a second submission with the US FDA for approval to manufacture albumin therapies at its new plasma production facility in Georgia, which when it goes online will increase production capability by about 30%.

The firm’s second-biggest sector – immunology – posted a 1% decline overall to $905m worldwide, due in part to new competition in the hemophilia space from Roche’s Hemlibra (emicizumab). (Also see "Hemlibra Effect Is Muted At Shire - For Now" - Scrip, 31 Jul, 2018.) Shire’s inhibitor product sales fell 37% year-over-year during the third quarter. Ornskov noted that sales of Feiba (anti-inhibitor coagulant complex) have been impacted by new competition in the US and some EU markets, without naming Hemlibra, but said the company is confident that its factor VIII products, Adynovate and Advate, can help offset those effects – though Hemlibra’s recent indication expansion means it will also compete in the non-inhibitor space.

“Our hemophilia sales grew 1% year-over-year with continued growth of our extended half-life product Adynovate,” the exec said. “We are ready for new competition in hemophilia and believe that personalized prophylaxis treatment with Advate and Adynovate continue to have a strong value proposition for patients.”

However, Morningstar analyst Karen Andersen predicted in an Oct. 29 note that Advate sales will begin eroding 10%-15% annually in 2019 as Hemlibra is launched in the non-inhibitor population.

Shire’s top-selling individual product, the ADHD therapy Vyvanse (lisdexamfetamine), posted global sales of $595m, up 11% from third quarter 2017, including $528.5m in the US. Overall, the neuroscience franchise brought in nearly $732m on the quarter, up 6%, with the recently launched ADHD drug Mydayis (mixed salts of a single-entity amphetamine product) yielding sales of $19.3m (US only).

Mydayis is key to Shire’s strategy for enduring the loss of US patent protection for Vyvanse in 2023. (Also see "Shire CEO: Mydayis To Be Big ADHD Drug, But No Ex-US Launch Planned (Yet)" - Scrip, 21 Jun, 2017.)

Looking To Takhzyro To Lead HAE Growth

But HAE is where Shire’s best growth prospects seem to reside at present. Takhzyro (lanadelumab-flyo), approved by the FDA in August, posted $51m in sales during its first month-plus on the market, which the company attributed mainly to stocking. Shire sees the therapy – the first monoclonal antibody approved for HAE prevention – as the key to winning back market share the past year to CSL Behring and its prophylactic Haegarda. (Also see "With Takhzyro Approval, Shire Could Reclaim HAE Prophylaxis Market From CSL Behring" - Scrip, 24 Aug, 2018.)

In a Nov. 1 note, Deutsche Bank analyst Richard Parkes said the initial Takhzyro revenue was about 5% above this modeling, due to “strong initial stocking.”

The company thinks Takhzyro will be well differentiated as a subcutaneous therapy that can be administered in less than one minute for most patients, and has a label recommending dosing every two weeks. The product also got approved in Canada on Sept. 20, and with a positive opinion Oct. 19 from the EU’s Committee for Medicinal Products for Human Use (CHMP), Shire expects a marketing authorization in Europe in December.

“While still early, we are encouraged by the response to the US launch,” Ornskov said. “Patients are coming from existing prophylaxis therapies, as well as patients new to prophylaxis. We have seen physicians prescribe Takhzyro who have not previously prescribed Cinryze. Our Quick Start program is enabling patients to start on therapy now while we engage with payers on their formulary updates.”

The Quick Start program is a bridging initiative enabling patients from lanadelumab clinical trials to continue on therapy while formulary adoption of Takhzyro gets worked out, he explained.

Overall, Shire’s HAE franchise has experienced ebbs and flows due to stocking trends and manufacturing issues. It posted 23% growth to $1.31bn in 2016 and was up 9% last year to $1.43bn. But Shire’s top-seller in the HAE portfolio – prophylactic Cinryze (C1 esterase inhibitor) – saw severe revenue fluctuations during 2017 and has trended downward quarter to quarter in 2018. In 2017, Cinryze revenues were as high as $229m in the fourth quarter and as low as $46m in the third quarter.

For the third quarter 2018, Cinryze brought in $117m, down sequentially from $136m in the second quarter. Firazyr (icatibant) totaled $140m for the third quarter and Kalbitor (ecallantide) $20m. Each carries an indication to treat acute HAE attacks.

Ornskov noted that most of Shire’s HAE sales this year are in the US – it brought in $12m ex-US for Cinryze and $26m for Firazyr. He attributed this to Cinryze supply constraints and said Takhzyro now offers Shire a chance to expand its HAE franchise globally.

Morningstar’s Andersen projects that Cinryze will continue declining, however, due to competition from Haegarda and Takhzyro, with the former also affecting Firazyr revenues. But Takhzyro will be a net positive for Shire’s HAE franchise, she said Oct. 29, as after a year of decline in 2018 the portfolio will post mid-to-high single-digit growth rates beginning in 2019, reaching $1.8bn total in 2022.

Chief Financial Officer Thomas Dittrich pointed out that while Cinryze declined sequentially, it more than doubled year-over-year as suppliers’ manufacturing issues were resolved. “In last quarter's earnings call, I told you that both Firazyr and Cinryze had significant stocking that would likely impact third quarter sales,” he said. “In Q3, we did see the expected destocking for Firazyr but not yet for Cinryze. Accordingly, we would expect Q4 Cinryze sales to be impacted by destocking.”