Reproxalap

Aldeyra Therapeutics plans to resubmit an approval application for its dry eye disease prospect in mid-2025 and expects a six-month FDA review. \n A phase 3 trial of Aldeyra Therapeutics’ dry eye disease prospect has hit its primary endpoint, preparing the biotech to seek approval for a candidate the FDA has rejected twice in recent years. Another phase 3 trial missed its primary endpoint, but Aldeyra said the data can still support its latest resubmission.Aldeyra first filed for FDA approval of reproxalap, which binds reactive aldehyde species, back in 2022. After the FDA demanded at least one additional symptom trial, the biotech started three studies and filed for approval again when the first readout was positive. The agency rejected the second submission in April and asked for positive data from at least one additional adequate and well-controlled study.The biotech shared top-line data from two studies after the market closed Monday, May 5. The dry eye chamber trial found reproxalap was statistically superior to the control on the primary endpoint, which looked at ocular discomfort.Aldeyra included data from another dry eye chamber trial in its second approval submission, but the FDA raised concerns about a baseline difference across treatment arms. The company said there were “no notable differences in baseline scores across treatment arms” in the second dry eye chamber trial and, as such, the study could potentially address the feedback the FDA shared in its complete response letter. Aldeyra plans to resubmit its approval application in mid-2025 and expects a six-month FDA review. The biotech is preparing to include data from the second dry eye chamber trial and from a recently finished field trial. Aldeyra shared top-line data from the field trial Monday, saying the trial was “numerically supportive of reproxalap and consistent with prior field trials, [but] did not reach statistical significance.”Draft FDA guidance states that chamber trials, which regulate temperature, air flow, humidity and other variables, and traditional environmental exposure studies can be acceptable in dry eye filings. Yet, there are no chamber data on the labels of the current crop of dry eye disease drugs. Aldeyra CEO Todd Brady, M.D., Ph.D., set out the pros and cons of relying on chamber data on a conference call with analysts in April.“It might be easier for the FDA to approve a drug based on a field trial simply because that\'s been the standard in the past. But I think there are advantages to having dry eye chamber data on our label,” Brady said. “I think our label would be compelling with either an additional field trial or a dry eye symptom trial from a dry eye chamber on the label.”

Aldeyra Therapeutics isn’t giving up on its drug candidate for dry eye disease despite a challenging path so far. The company is preparing to file reproxalap with the FDA for the third time after a primary endpoint hit in its latest Phase 3 study. The Lexington, MA-based biotech’s 0.25% reproxalap ophthalmic solution “significantly” improved ocular discomfort versus vehicle only, according to a late Monday release . The Phase 3 trial enrolled 116 people with dry eye disease and exposed them to a controlled low-humidity environment — also known as a “dry eye chamber” — to trigger their symptoms. Aldeyra said the data should address concerns raised by the FDA in a complete response letter issued last month. That letter said Aldeyra “failed to demonstrate efficacy in adequate and well controlled studies.” In particular, the agency noted that baseline differences in patients across treatment arms in a separate Phase 3 chamber study may have impacted the interpretation of results. But Monday’s latest Phase 3 data “included no notable differences in baseline scores across treatment arms,” according to the release. Aldeyra has conducted multiple Phase 3 tests of reproxalap in dry eye disease but the first one, which read out in 2021, was unsuccessful . Aldeyra plans to resubmit the NDA in the middle of the year. That would mark its third attempt at getting reproxalap across the finish line. The drug met its first rejection in November 2023 when the FDA requested another clinical trial to provide more efficacy data. Aldeyra conducted the trial and filed reproxalap for the second time in 2024, only to be hit with the CRL in April. Despite the setbacks, Aldeyra’s partner AbbVie is still on board. In November 2024, the companies expanded the scope of an option agreement for reproxalap that was first inked in 2023. If the drug is approved, AbbVie will have 10 business days to opt into a co-exclusive license to develop, manufacture and commercialize the drug. The milestone would also trigger a $100 million milestone payment for Aldeyra.