FDA Rejects Evolus’ Botox Knockoff for Now

Clinical Trials Failure

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter to Irvine, California-based Evolus for its Biologics License Application (BLA) for DWP-450 (prabotulinumtoxinA), a drug to treat frown lines similar to Allergan’s Botox.

The company presented results of its Phase III head-to-head comparative trial of EVB-003 at the 2018 Aesthetic & Anti-Aging Medicine World Congress (AMWC) in Monte-Carlo, Monaco in April, expanding on data presented in February at the American Academy of Dermatology (AAD) meeting, showing “non-inferiority” to Botox (onabotulinumtoxinA). The product is also under review by the European Medicines Agency (EMA).

In the CRL, the FDA cited problems related to Chemistry, Manufacturing, and Controls (CMC) processes, not clinical or non-clinical issues. The company expects to respond with a complete submission within 90 days.

The FDA also issued an Establishment Inspection Report (EIR) to Daewoong Pharmaceutical as part of a pre-approval inspection of the South Korean manufacturing facility that was built to produce DWP-450. It has been fully validated under current good manufacturing practice (cGMP) requirements.

In a note to investors, Louise Chen, an analyst with Cantor Fitzgerald, indicated that due to a “form 438” issued after 2017 inspections, the CRL was not unexpected, but approval was likely by late summer.

Reuters observed, “A likely delay in the commercial launch of the product would be a positive for Allergan, which is expected to face competition from other products, including a biosimilar from Revance Therapeutics.”

In February, Mylan and Revance Therapeutics announced a global collaboration and license deal to develop and commercialize a biosimilar to Botox. It included an upfront payment of $25 million to Revance, contingent milestone payments and royalties in relevant markets.

“This will be a significant opportunity for Mylan as we add another difficult-to-manufacture product to our pipeline,” Mylan president Rajif Malik said in a statement in February. “We have reviewed the work done to date by Revance and we are extremely excited and confident about our ability to bring this important product to market. Bringing an affordable biosimilar version of Botox to commercialization will offer patients a safe alternative to this popular and highly effective treatment.”

Evolus has at least one more hurdle before approval, and once that happens, has to convince doctors to prescribe their version of the drug. Botox controls about 90 percent of the botulinum toxin market in the U.S. and more than 70 percent worldwide. It’s a brand known to most people, even if they have no interest or need for it.

Seeking Alpha notes, “Evolus needs to generate sales as soon as possible in In Q1 2018 it suffered an operating loss of $6 million. It raised over $56 million from an initial public offering earlier this year. Cash on hand was $50 million at the end of the quarter. Cash will likely continue to fall until the company receives regulatory approval for DWP-450 and can commercialize the treatment.”

Allergan’s Botox brought in $817 million in sales the first quarter of this year, with $573 coming from the U.S. The total U.S. market is projected at about $2.5 billion, and appears to be growing about 13 percent year-over-year. If Evolus can get its product approved and offer big discounts compared to Botox, it could eat up a part of that market, at least until Mylan and Revance get their competitive product onto the market.

David Moatazedi, president and chief executive officer of Evolus, stated, “We are pleased with the progress we continue to make with the FDA, and this CRL confirms our confidence in our clinical submission. Deficiencies cited within the CRL are isolated to CMC matters and we expect to respond comprehensively within 90 days. Overall, we view these updates as positive, which together give us the line of sight necessary to build our commercial infrastructure. We look forward to working closely with the FDA and remain committed to bringing DWP-450 to market by spring 2019.”

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