FDA hits Leo Pharma with a CRL for what the biotech says are questions about the 'device component' of eczema candidate
After toiling away for the last few years on a monoclonal antibody to compete with Dupixent in atopic dermatitis, Leo Pharma has been hit with a complete response letter from the FDA.
The agency has “requested additional data relating to a device component of tralokinumab,” Leo said on Thursday, but the biotech didn’t share any further details on the device or what went wrong. Company spokesperson Henrik Kyndlev declined to provide more information via email, but said Leo is “looking forward to meet with the FDA to clarify details about the request.”
As for the safety and efficacy of the drug, Leo was on the defensive: “FDA did not request any new data on the clinical efficacy or safety of the drug product formulation of tralokinumab,” the company said in a statement.
It’s worth noting that drugmakers hit with a CRL often obscure information about the contents of those letters in public statements, in many cases omitting the agency’s safety and efficacy concerns, according to a study published in The BMJ in 2015. In that analysis, just 14% of companies’ press release statements after a CRL actually matched the concerns contained in the letters, which aren’t made public.
Kyndlev declined to share a copy of the CRL with Endpoints “as it is an ongoing regulatory process,” but reaffirmed that the FDA’s request is “only related to the device component.”
Tralokinumab comes from AstraZeneca’s pipeline, where it flopped in three Phase IIIs for asthma patients before Pascal Soriot gave it the boot. Leo put down $115 million for rights to the monoclonal antibody plus another dermatology candidate back in 2016 — promising up to $1 billion in milestones — and set out to develop it as an atopic dermatitis therapy.
The Danish biotech announced tralokinumab swept up positive results for all primary and secondary endpoints in three Phase III trials in December 2019, but some were skeptical of the timing. Evercore ISI’s Umer Raffat said it appeared that Leo had been sitting on the results for about a year, which is never a good sign.
Leo’s communications team, however, told Endpoints that Raffat was wrong about the yearlong delay, adding that the trials were scheduled to wrap up in a series and they were waiting for the full data, which weren’t available for analysis until November 2019.
While it’s standard procedure in the industry to report data by trial as they become available, the spokesperson said Leo didn’t release any hard data to avoid damaging their chances of getting the data published in a peer-reviewed journal.
Leo submitted the BLA for tralokinumab back in July, and says it was handed a target action date in Q2 2021.
Earlier this month, Leo read out long-term data from an open-label extension trial dubbed ECZTEND. In a two-year cohort of patients who completed 52 weeks of tralokinumab treatment in parent Phase III studies ECZTRA 1 and 2 and at least 56 weeks in ECZTEND, 93.8% achieved at least a 50% improvement in Eczema Area and Severity Index score (EASI-50). A total of 82.5% achieved EASI-75, and 59.8% achieved EASI-90, according to Leo.
Tralokinumab targets IL-13, which Leo says plays a key role in the immune process behind atopic dermatitis signs and symptoms. Dupixent, the giant in the field, blocks both IL-13 and IL-4. Eli Lilly snagged its own IL-13 contender, lebrikizumab, in the $1.1 billion Dermira buyout. That candidate is now in Phase III.
Earlier this month, the FDA extended its review period for AbbVie’s Rinvoq in atopic dermatitis, requesting “an updated assessment of the benefit-risk profile,” according to the drugmaker.