Lev wins approval for first HAE treatment in US

Lev Pharmaceuticals has won FDA approval to launch the first drug to specifically treat the rare swelling disorder hereditary angioedema (HAE) in the US; an important victory because despite the niche indication, a number of competing products are also close to the market.

The drug, called Cinryze, is differentiated from the potential competition in that it can only be used, initially at least, as a prophylactic or preventative treatment. Administered via infusion three or four times a week, the drug has been proven to prevent the sudden, painful swelling attacks which some patients suffer several times a month. This unique selling point was the reason why Viropharma launched a takeover bid for Lev in July, a deal which now looks certain to close at the end of this month.

Cinryze, a protein replacement therapy, has orphan drug status and thus will receive marketing exclusivity for seven years in prophylactic use. The company had also sought approval in the acute setting, but announced on Friday that this application has been withdrawn, and will be resubmitted as soon as possible with additional data.

Race still on

Lev said it does not anticipate further trials being demanded, but this could be a moot point, since another very similar replacement therapy made by CSL Behring called Berinert is awaiting approval in the acute setting. Berinert also has orphan status, and their similar mode of action, replacing the missing C1 inhibitor protien in HAE patients, means whoever wins approval first will effectively block the other from the market as an acute treatment.

However, CSL’s PDUFA date of September 5 has passed with no news. Since the acute setting is believed to be more valuable than prophylactic, because only patients with very severe HAE are likely to be prepared to go through the infusion process, a delay for CSL would be encouraging news for Lev and Viropharma.

Sigh of relief

Viropharma shares bounced 15% higher in early trade today to $11, no doubt to a certain extent staging a recovery along with the rest of the battered stock market. However, the regulatory clearance announced late Friday should spark sighs of relief for many of the company’s shareholders, not all of whom greeted the decision to buy Lev with enthusiasm.

That was for a number of reasons, one being that HAE is a niche drug, with only 4,600 diagnosed sufferers in the US, and a number of products are nearing the market simultaneously. While the condition is believed to be under diagnosed, true demand is hard to gauge, particularly in the prophylactic setting. Hence the lack of reliable sales forecasts to justify the potential $617m price tag initially caused concern.

Licensing structure

Because the acquisition of Lev was structured more like a licensing deal, the groups’ shareholders will receive more cash further down the line if certain milestones are met. One, worth another 50 cents a share, will be paid if Cinryze is approved for acute treatment and wins orphan exclusivity, to the exclusion of other replacement therapies, or if no directly competing products wins orphan exclusivity in acute for two years.

That eventuality is certainly not out of the question yet, and news from CSL will be closely watched.

Another payment of the same value will be payable when Cinryze reaches at least $600m in cumulative net sales within 10 years of closing. Viropharma believes Cinryze has peak sales potential of $250-$300m a year, which makes that milestone look achievable.

However, much will ride on the performance of the other HAE treatments waiting in the wings. Dyax has DX-88, which should be filed later this year, while Shire’s Icatibant is not far behind. Their different modes of action to the replacement therapies means they will not be blocked from launching immediately.

As small molecule approaches with simpler modes of administration, these drugs will represent a far greater threat to which ever protein replacement therapy wins exclusivity in the acute setting. Lev and Viropharma can claim to have won the race, an undoubtedly important acheivement, but domination of the market is far from guaranteed.

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