The Staccato technology and loxapine that make up AZ-004 will be on display on October 11th as Alexza (ALXA) looks for approval from the FDA. My previous article focused on how Alexza was clearing hurdles to move into a strong position with the FDA. What this article will do is discuss the history of the Staccato technology and its applicability and use in drug delivery with specific emphasis on AZ-004.
Alexza and the Staccato technology was founded by Dr. Alex Zaffaroni. The company was built on the concept of the Staccato technology in use for treating acute and intermittent conditions. Alexza has developed a deep pipeline of products in a short period of time as they have put 5 products into the clinic in only 4 years. Capital constraints have caused Alexza to focus on AZ-004 in 2010. They have (pdf) two migraine programs, a pain program, AZ-002 Staccato alprazolane which they studied for panic, and AZ-007 which is part of their sleep program.
The Staccato system vaporizes drugs instantaneously to create aerosols that look like you have given someone an injection (Staccato Technology Animation Video).
They put a thin layer of the very pure drug, API, on the surface of stainless steel, and they heat it up instantaneously. The drug goes from solid to gas, cools, condenses, and comes out at the end of the device. This thorough process takes less than a half-second. The first 1/3 of the first breath through the device does all that work and then delivers a highly reproducible dose of drug deep into the lung. 5 programs are on this simple dosing device which basically consists of a heat package. This heat package (pdf) uses energetic materials to create the energy to create the aerosol using a simple printed circuit board, a battery, and a plastic casing aroud it.
The Staccato has been discussed by the CEO (Tom King) as a “quantum leap” in how one should think about inhalation technology. In addition to mimicking intravenous like pharmacokinetics, it has been demonstrated in two crossover studies that Staccato inhalation looks just like giving an IV injection. The technology is proprietary because of the way they create the aerosols. There is a high degree of purity with a really focused particle size. They create particles with the collision of aerosol that are in the 1-3 micron size. That size is perfect for deep lung inhalation. There are no excipients so nothing is in the aerosol other than pure drug. It can be water soluble or insoluble. The benefit of exploring man drugs is that historically they could not be given intravenously because they were water insoluble but they could give them because they mimic an IV injection. The Staccato has reliability and consistent delivery. More than 80% of the drug consistently comes out of the device every-time one inhales on it. The CEO has stated in conferences that everyone could inhale on a different device and they would all get the same amount of drug every time. There is not another inhalation technology around that has the consistency and reliability in terms of delivery of aerosols.
The advantage of the broad applicability of the Staccato is that Alexza has screened over 400 drugs and there are 200 that work with the technology. Alexza has 6 INDs in 4 years; dosed over 2,600 patients in 5 different therapeutic areas; and has obtained over 175 issued and allowed U.S. and International patents. Alexza right now is at a point in their company's existence. Alexza filed their first NDA last December 2009; obtained their first partnership for commercialization of AZ-004 with Biovail in February 2010. Their PDUFA date was granted and is October 11th, 2010. My next article will focus on the agitation market, loxapine, and clinical studies submitted to the FDA for approval of AZ-004. 2010 could be the start of a new platform for inhalation technology with the Staccato system if the FDA approves AZ-004 in the next month.
Disclosure: Long ALXA