Biofrontera overcomes combination product hurdles to enter US market

German biopharmaceutical company Biofrontera has finally cracked the US market with its combination product, gaining access to 58 million Americans with actinic keratosis.

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There are many moving parts for Biofrontera, a drug and device company specializing in sun-induced skin cancer. With just 60 employees, it has navigated E.U., and U.S., regulatory approval processes, bringing to market both a topical prescription cream, Ameluz, and a photodynamic medical device, BF-RhodoLED, for the treatment of actinic keratosis (AK).

But the approval process has not come easily due to challenges on each side of the Atlantic.

Biofrontera was founded by its current CEO, Hermann Lübbert, in 1997. A Novartis alumni, Lübbert licensed a technology platform and began developing it in Leverkusen, Germany with some pharmaceutical partners.

In 2005, the company decided to undergo a “strategic change,” which involved throwing out all existing work and undergoing a rebirth as a dermatological company. The u-turn appears to have delivered with Biofrontera having developed a line of cosmeceuticals, alongside its two lead drug/device candidates, Ameluz and BF-RhodoLED.

By 2012, both of Biofrontera’s AK therapies were approved throughout the E.U. for separate or combined use — but the company has struggled with reimbursement, Lübbert said in a recent phone interview.

During this time, the lucrative U.S. market remained out of reach, sequestered behind a complex approval process. Biofrontera’s dual offering is categorized by the FDA as a “cross-labeled combination product,” which means the components are sold separately but labeled for use together.

The U.S. is unique in requiring cross-labeled products to be approved as a combination therapy. To do so, Biofrontera had to rally more resources and embark upon new clinical trials to prove the safety and efficacy of the drug-device combo.

Biofrontera’s combination product was eventually approved in May 2016. By then, Lübbert said, some fundamental scientific beliefs about the condition had changed.

An estimated 58 million Americans are affected by actinic keratosis. The condition presents as a series of precancerous lesions that appear in areas frequently exposed to the sun, including the face, neck, and hands. Left untreated, up to ten percent of AK lesions will develop into squamous cell carcinoma (SCC), the second most common form of skin cancer.

“In the past people believed that it’s a sort of continuum, so you have the mild actinic keratosis and if it’s severe, it may progress to squamous cell carcinoma,” Lübbert said. “If that’s the case, then it’s sufficient to treat only the severe ones [lesions] because the mild and moderate cases are not that dangerous.”

Evidence has since been presented in the scientific literature that suggests the reverse is true. Lübbert said the consensus now is that “the mild or even the subclinical — so not yet visible — actinic keratoses has a higher chance of progressing to squamous cell carcinoma. That of course, must change the way the optimal treatment is performed.”

As a result of these findings, the dermatological paradigm has shifted towards regional treatments. Rather than freezing or surgically removing targeted lesions, Lübbert said the aim is to treat the wider area, anticipating that the skin there will also be damaged.

In this light, the market for AK therapies is very strong. According to the Skin Cancer Foundation, people with a fair complexion, hair, and eyes that spend significant amounts of time in the sun have a “high likelihood of developing AKs” as they age. Once presented, the patient will likely need intermittent treatment for the remainder of their life.

Despite the enormity of the U.S. market, just a few small players occupy the space. According to Lübbert, Biofrontera’s main competitor in the U.S. is DUSA Pharmaceuticals, which was acquired by Sun Pharmaceuticals in 2012. DUSA manufactures Levulan Kerastick and Blu-U PDT, a similar combination of a topical cream and a phototherapy device.

Lübbert believes Biofrontera will have an edge, as it expands its presence in the U.S. Ameluz is easy to apply and the phototherapy device adequately targets AK regions, he said. Once established, there are countless other nations with high rates of actinic keratosis, which will likely be easier to enter.

Photo: simarik, Getty Images