Editor’s note: Welcome to Editors' (re)View, our editors’ takes on things going on in the pharma world that deserve some extra consideration.
FDA turns up its nose at Neffy
This week, we reported that the FDA issued a CRL for ARS Pharma’s epinephrine nasal spray — a move that seemed to take the company by surprise. The rejection was unexpected considering that the FDA's AdComm has voted in favor of approval of the drug — dubbed Neffy — for both adults and children back in May 2023.
In the CRL, the FDA requested more data on repeat dosage, specifically asking that ARS complete a pharmacokinetic /pharmacodynamic study assessing repeat doses of Neffy compared to repeat doses of an epinephrine injection product. On one hand, the request makes sense because there are certainly instances where a single dose of epinephrine does not relieve symptoms and a second dose is required — in the AdComm meeting, one presenter estimated 20% of anaphylaxis cases require a second dose .
However, according the ARS, the company and the agency agreed last month that the repeat dose study would be conducted as a post-marketing requirement for labeling purposes. And for ARS, the change in plans further complicates what has already been a complex approval process.
Epinephrine has been used for over 100 years for the treatment of allergic reactions and anaphylaxis, which means it predates the Food & Drug Cosmetic Act of 1938 that required marketed drugs to demonstrate safety and the 1962 amendment to that act that required drugmakers to also prove efficacy.
In fact, controlled clinical trials have never been conducted for any epinephrine products, mostly for ethical reasons. A time-sensitive emergency is not easy to test, especially when the consequence of the drug failing can be fatal. In 1987, EpiPen was approved by FDA based on literature support for efficacy and safety — no clinical trials and PK/PD data were required.
Following suit, clinical efficacy trials were not included in the development of Neffy, with ARS citing feasibility and ethical concerns. Instead, ARS ran several studies to generate surrogate data aimed at figuring out whether the spray could be as effective as injections, testing in both healthy patients and allergy sufferers.
It's a tricky scenario for regulators. The agency doesn’t want to sign off on something used in life-threatening scenarios if a more effective option already exists. However, EpiPens can’t save lives if people don’t use them and there are various barriers to epinephrine auto-injector use. People are often hesistant to use anything with a needle and EpiPens also aren’t the easiest to transport — studies have found that close to 60% of patients don’t carry the pens on them.
ARS anticipates a resubmission to the FDA in the first half of 2024, positioning the company for decision in the second half of 2024 — it will be interesting to see how it all unfolds. —Karen Langhauser
Mesoblast comes closer to winning
A few weeks ago, when I wrote up news about how Mesoblast executives were taking pay cuts to support the development of their lead asset, I found myself rooting for their success. This week, after many regulatory hurdles, Mesoblast shared updates from its latest Type A meeting with the FDA — and things appear to be looking up.
The drug is thought to work by reducing the production of pro-inflammatory cytokines, boosting the production of anti-inflammatory cytokines, and facilitating the recruitment of naturally occurring anti-inflammatory cells to affected tissues.
First rejected in 2020, and then again this year, the FDA insisted that the company needed to provide data on at least one additional randomized, controlled study in adults and/or children to provide further evidence of effectiveness. Mesoblast resubmitted in January 2023, including long-term follow-up data showing 50% survival over more than four years for patients treated with the drug, but still the agency requested more data to support marketing approval.
Now, the two are working together to address proposed trial designs for adults and to see the application through. The company will receive official minutes from the meeting within three weeks.
— Andrea Corona
