By Henry Ehrlich
By Henry Ehrlich
Last September I wrote a piece about AR101, the oral immunotherapy product under study by Aimmune Therapeutics. It was based on a couple of viewings of an investor presentation by the firm’s CEO and as I said at the time, I could have made some mistakes but the video was removed before I had a final crack at checking my assertions and invited the company to respond. Eight months later someone did get back to me.
The key clarification was about my assertion that the product contained only three of the allergenic proteins, which was at worst a good faith interpretation of something I thought I heard but couldn’t verify. This was then picked up by others. (I would still like to view the original.)
In April, I received notice from the company’s spokesperson to correct the error and providing a very thoughtful rationale for the chosen methods:
Explanation of AR101 and Ara h1, Ara h2 and Ara h6 (molecular fingerprint):
We believe that a successful oral desensitization treatment regimen requires a well-characterized and precisely manufactured drug product. Independent scientific research has shown that the quantity of peanut protein and the relative concentrations of key peanut proteins can vary widely among the different commercially available peanut products that could potentially be used as a source for oral desensitization therapy. These variations could significantly impact the reliability and safety of an oral desensitization treatment regimen.
To reduce the potential for variability, we chose to use peanut flour solely from the Golden Peanut Company as the basis for AR101. This flour has been used in most of the leading academic studies of peanut allergy OIT and, based on our own testing, shows little variation in the level of peanut protein in different batches of the company’s flour, including among batches produced in different years. Also, because Golden Peanut’s products are used so widely among food manufacturers in the United States, we believe their flour is representative of a type of peanut protein that patients might encounter in an accidental exposure.
We took the further step of precisely characterizing the protein signature of Golden Peanut’s flour. Independent scientific research has identified numerous peanut proteins that are the allergens that cause allergic reactions to peanuts. As you know, three of these proteins – Ara h1, Ara h2, and Ara h6 – appear to be the most significant, and they are also representative of the levels of the other proteins. Our characterization of AR101 is based on precisely measuring total protein amount and the concentrations of those three key proteins.
Through our contract manufacturers, we are capable of producing dosages with protein content as small as 0.5 mg, and we have developed advanced analytical methods to ensure each dose contains precisely defined amounts of well-characterized allergenic proteins. Our manufacturing processes maintain all of the naturally occurring peanut proteins. Our formulations are also designed to ensure that the drug product is acceptably stable and can be easily mixed with food.
You may find it interesting to learn that because peanut flour is a sensitizing agent, AR101 must be produced on a manufacturing line that is physically separated from other manufacturing lines and that has its own ventilation system.
I also questioned the way the product would be provided through allergists. My particular concern was whether it would be given to patients without fully ascertaining if it would be useful or if it might be prescribed to patients for whom it had no medical relevance, as inhaled corticosteroids and combination inhalers often are given to patients who don’t have the right kind of asthma. (In fact, this was the reason I reached out to Dr. Andrew Bird to write the piece that we published in November called Food Allergy Testing in the Coming Age of Immunotherapy. Little did I know that Dr. Bird is on a very distinguished team of leading allergy doctors who have taken part in AR101 studies as principal investigators at clinical sites, although they are not employees of Aimmune.)
The company is preparing rigorous support protocols during up-dosing and maintenance.
As it was explained to me:
We believe that it is important to support food allergy awareness and safety and the understanding that food allergy is a potentially life-threatening disease – in other words, food allergy should be recognized as a medical condition and have the appropriate medical services surrounding it. Consistent with that, we are working on packaging for both up-dosing and maintenance that is designed to aid compliance via easily trackable calendar blister-packs. Our goal with the maintenance dose is to support the level of desensitization to protect against reactions to accidental exposures and make compliance as easy as possible, with a low dose minimizing bulk and taste impact (for those averse to peanuts) – as compliance is essential to maintain protection.
So, thanks to Aimmune for reaching out. I believe that this will be a useful therapy for many patients, particularly as they start to extend their product line to other allergens. The company acknowledges that it is not a cure but that it will provide relief for many as the science marches on. I hereby eat a couple of my words.