After resounding backing from an FDA advisory panel earlier this year US approval for Shire’s Firazyr, granted yesterday, was not a huge surprise. But as the fourth product to treat the rare swelling condition hereditary angioedema to reach the US market within three years, the British drug maker will have to fight hard for a share of this small and competitive market.
The product has an important differentiation in that it can be self-administered, and since this feature was approved by European regulators in March Shire has seen an impact, Sylvie Grégoire, president of the company’s human genetic therapies unit, tells EP Vantage. However, overall uptake has been resoundingly disappointing in Europe since launch in 2008 – in total the product has only generated sales of $29m – and a much better performance is needed from the US launch.
Most analysts believe that the situation in the US is likely to be very different, with self-administration on the label from day one. Reimbursement issues, which hobbled demand in Europe, are also not anticipated. The table below shows that on average sales of $175m are anticipated by 2016, according to consensus data from EvaluatePharma, a figure that could rise now US approval is in the bag.
Firazyr will compete directly in the acute setting with subcutaneous Kalbitor and infusion therapy Berinert – Cinryze, also an infusion therapy, is approved only in a prophylactic setting, used mostly by patients who suffer very regular attacks of the swelling condition.
With the efficacy of the three acute treatments broadly similar in terms of the time they take to bring swelling under control, convenience factors are crucial. Berinert must be infused in hospital, while Kalbitor needs to be reconstituted before injection and stored in a refrigerator. Its black box warning about the potential for anaphylactic reactions also means it has to be administered by a healthcare professional, ruling out home use.
Firazyr is stored at room temperature and can be administered immediately a patient feels signs that an attack is beginning. With no real hurdles for a patient to start self injecting, and home use eliminating what can be expensive trips to the emergency room in the US, Shire is convinced the product will do well.
“We think Firazyr will take a good part of the market because it serves an unmet need in terms of rapidity of access to treatment,” says Ms Grégoire. “In terms of value the market as a whole its still evolving. Where it will get to, in terms of market value, and who gets what market share, it is still too early to tell.”
Although the arrival of these new products in the US – where only prophylactic steroid treatment was available before the approval of Cinryze and Berinert – is improving awareness of the disease, under diagnosis is still a problem, Ms Grégoire says.
“On average these patients are diagnosed about 17 years after their first attack. The advent of treatment has increased awareness, but you have to have awareness at the level of primary physicians to expect that, and that will take a longer time than a couple of years,” she says.
It is estimated that 30,000 patients worldwide suffer from hereditary angioedema, characterised by a low levels or a dysfunction of the enzyme C1 esterase inhibitor, which leaves sufferers prone to attacks of swelling in the face, abdomen and genitals – swelling in the larynx can be fatal. The US is thought to account for a third of these patients; Shire believes only half are currently diagnosed.
This certainly describes a niche market, and with four products now available in the US competition is likely to be intense. Still, Ms Grégoire argues that there is room for all these players.
“It’s a rare disease but not as rare as some others. If you think about Fabry and Gaucher diseases, they have patients in the low thousands in terms of prevalence. This disease can tolerate more competitors particularly if some products don’t address all unmet needs in terms of how they are administered or how the disease manifests itself. That will prompt the arrival of further competitors, even in the rare disease space,” she says.
While there is unsurprisingly little else in the pipeline for HAE following the glut of approvals of the last few years, incumbents are still working on improvements to their offerings. For example ViroPharma is developing a subcutaneous formulation of Cinryze, which will yield phase II results next year and prompt a decision from the company on whether to move into pivotal studies.
Shire meanwhile is working on more convenient routes of administration for Firazyr, Ms Grégoire says, as well as other forms of angioedema.
Each new arrival on the HAE market has offered something new and Firazry is no different. But the small market is undoubtedly crowded and initial demand will be closely watched, as Shire strives to make the impact in the US that failed to materialise in Europe.
|HAE market||Annual Sales WW ($m)|
|Product||Company||Generic Name||2010||2012||2014||2016||Launch US||Launch Europe|
|Cinryze||ViroPharma||C1 esterase inhibitor (human)||177||332||471||570||2009||2011|
|Berinert P||CSL||C1 esterase inhibitor (human)||*91||125||165||195||2009||2010|
|Rhucin/Ruconest||Pharming/Swedish Orphan/Santarus/Esteve||conestat alfa||**0.9||-||8||29||2013||2010|
|*CSL does not announce sales, figures based on Cowen estimates|
|**Figures based on 2010 sales announced by Pharming, forecast data only available for Santarus which owns US rights|