The FDA issued complete response letters (CRLs) to two companies in recent days, resulting in vastly different reactions from the market.
The U.S. regulator rejected Pharming’s bid to gain an expansion for Joenja to treat patients ages 4 to 11 with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare immunodeficiency. With the thumbs down, Pharming’s share price tumbled by 16% on Monday.
Meanwhile, the FDA also swatted away Aquestive Therapeutics’ new drug application for Anaphylm sublingual film for the treatment of Type 1 allergic reactions, including anaphylaxis, in patients weighing at least 30 kg (66 pounds). But with the red light, Aquestive’s share price increased by 35%.
The reason for the optimism on Anaphylm? The FDA’s concerns with the rescue treatment were limited to its packaging, administration and labeling guidance.
“While it is unfortunate to have received a CRL, we believe that, with the clarity we now have from the FDA, we have made significant progress toward approval,” Dan Barber, the CEO of Aquestive, said in a release.
The regulator cited difficulties in opening Anaphylm’s pouch and the potential for incorrect film placement, which “the FDA believes could cause significant safety issues in the setting of anaphylaxis,” Aquestive said in a release.
“This opening is the one we use with multiple other products that are on the market and one product that’s been on the market for 15 years,” Barber said during a conference call on Monday morning. “It’s a bit of a head scratcher, but we’ll do the work that the FDA has requested.”
Aquestive said it has already modified the pouch opening, its instructions for the drug's use and the labeling on its carton. The company will also conduct a new human factors validation study and plans to address potential tolerability issues with its resubmission, which could happen as early as the third quarter, it added.
As a needle-free, oral epinephrine option, Anaphylm has been pegged as a potential blockbuster and a game-changer for the New Jersey-based company, which projected in November that its 2025 revenue would come in at between $44 million and $50 million.
The CRL does not affect submissions for approval of the treatment in Europe and Canada, which are still on track by the end of this year, Aquestive said.
Pharming rejection
In the CRL the FDA sent to Pharming, the agency cited the potential for “underexposure” in lower-weight patients and has requested additional pediatric pharmacokinetic (PK) data, the company said. The FDA wants to reassess the proposed pediatric doses and confirm that children in the lower-weight dose groups can achieve exposure levels comparable to the approved regimen. The letter also identified an issue with one of the analytical methods used for production batch testing.
“While we are disappointed in the FDA’s response, we remain dedicated to making Joenja available to pediatric patients aged 4-11 with APDS,” Fabrice Chouraqui, the CEO of the Netherlands-based company, said in a release. “We are going to work closely with the FDA to provide the necessary information and determine the best and most effective path forward.”
The company said it believes it can address the PK and batch testing methodology issues and will request a Type A meeting with the FDA.
Analysts from Jefferies noted that “importantly,” the CRL did not reflect any efficacy concerns, indicating that the drug will likely eventually gain approval for the age group. Jefferies added that a third-quarter approval would be a “best-case” scenario at this stage.
More information could be available during the company’s investor presentation on Tuesday. Last month, Pharming reported (PDF) preliminary 2025 revenues of $376 million, up 27% from 2024. Through three quarters, Joenja—which was approved in 2023—had produced sales of $38 million, with $15 million coming in the third quarter.
The big seller for Pharming is Ruconest, which generated sales of $231 million through the first nine months of 2025. The treatment was approved in 2014 for hereditary angioedema.