- The Food and Drug Administration rejected Aradigm Corp.'s inhaled version of the antibiotic ciprofloxacin, issuing a Complete Response Letter (CRL) to the California-based biotech that asks for an additional Phase 3 study of the drug, called Linhaliq.
- The regulator's thumbs down doesn't come as a surprise, as it follows an advisory panel vote in early January which opposed approval of Linhaliq for a type of chronic lung infection. Still, rejection of the drug — and the costly further study demanded by the FDA — puts Aradigm in a bind.
- Shares in the biotech fell 20% Monday morning, and are down more than 75% since the stock's recent peak in late December. Aradigm still plans to submit Linhaliq for approval in the European Union, yet FDA rejection raises questions about the company's ability to fund research moving forward.
Aradigm's research efforts have focused on two inhaled formulations of ciprofloxacin: a slow release version designed for the treatment of chronic lung infections involving Pseudomonas aeruginosa in individuals with non-cystic fibrosis bronchiectasis (NCFBE) and another aimed at management of infections in cystic fibrosis patients.
Data from two Phase 3 studies of Linhaliq in NCFBE were mixed. One, called ORBIT-4, showed treatment with Linhaliq significantly lengthened the median time to first mild, moderate or severe pulmonary exacerbation. Results from the other, ORBIT-3, was not statistically significant — although the treatment arm saw a numerical advantage.
Independent experts on the FDA's Antimicrobial Drugs Advisory Committee were not convinced by the totality of Aradigm's evidence, voting 12 to 3 against recommending approval of Linhaliq.
In its CRL, the FDA requested Aradigm complete a third Phase 3 study testing Linhaliq's efficacy over a minimum duration of two years. The agency also asked for further study of human factors related to packaging and for additional product quality information.
Meeting those requirements will require a substantial amount of resources. As of September 30 last year, Aradigm listed $12.6 million in cash and equivalents, which it estimated could fund operations at least through 2017. Yet, the financial situation was precarious enough for the company to caution that some doubt would exist around its ability to continue as a going concern if it was unable to raise further money.
Rejection of Linhaliq means Aradigm won't receive a $5 million milestone payment from Grifols Inc. under a prior license agreement.
Aradigm said it would request a meeting with the FDA to discuss the CRL and to develop plans for a resubmission of Linhaliq as soon as possible.
"Our focus is also on the submission in the near future for marketing approval in the European Union," said company CEO Igor Gonda in a Jan. 29 statement.
Shares in Aradigm were trading below $2 a share Monday morning.