Gonda, Ph.D., joined Hayward, Calif.-based specialty pharmaceutical company Aradigm Corp. from Genentech, where he led a team focused on developing inhalation products for severe respiratory disease. Today, Gonda leads Aradigm scientists on a mission to revolutionize the quality of life of patients with severe pulmonary disease. The Aradigm team pioneered the AERx iDMS pulmonary delivery of insulin that was used in Phase 3 clinical trials conducted by Novo Nordisk. Now, Aradigm is uniquely positioned to develop a portfolio of its own products to treat patients with severe respiratory diseases. Current activities include development programs addressing the treatments of bronchiectasis, cystic fibrosis, inhaled bioterrorism infections and smoking cessation.
Q: Share with me a short history of Aradigm.
A: Aradigm was a venture-founded company and we went public in 1996. We were at one point a very large company with about 400 employees and we had very large manufacturing operations focused on the development of pain management therapies and inhaled insulin. Then, the inhaled insulin program was taken over by Novo Nordisk. The deal, however, was later terminated. The company completely changed its view of how we should operate.
So, now, we are mostly virtual. We kept the intellectual property and the know-how of the company and, now, have 12 people. The core of the company is basically the R&D group that I brought with me from Genentech. We also brought a medical director who was a former Roche employee. He was working on the same Genentech product that we were working on, which is the first modern drug that was approved for cystic fibrosis patients.
Q: What are some of the limitations in lung disease therapies that Aradigm is addressing today?
A: The common denominator, particularly for cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease, is that the severity of the disease rapidly grows when these people get an infection with a particular microorganism called Pseudomonas aeruginosa. There has been a strong association between severity of the disease and reduced life expectancy and a person’s colonization with this microorganism. About 80 percent of adult cystic fibrosis patients are colonized with Pseudomonas aeruginosa.
There are two products approved, two inhalation antibiotics, for the treatment of Pseudomonas aeruginosa patients in cystic fibrosis. The problem that these patients with cystic fibrosis have is that they are spending enormous amount of time just treating their disease, and, because they are born with the disease, typically, for many years, it is not just a job for the patient, but it is the job for the families who look after them and some of these families have more than one cystic fibrosis child. So, it is a huge burden that the disease imposes on the patient and on the family.
Our idea, initially, was very simple and that was to provide cystic fibrosis patients with a once-daily inhaled antibiotic. One of the antibiotics that is approved is twice-a-day and the other one is three times a day.
Q: Talk a little about how you became involved in developing treatments for bronchiectasis (brong-ke-EK-ta-sis), a condition in which damage to the airways causes them to widen and become flabby and scarred?
A. This is a program we feel particularly proud about because it is a totally unmet medical need and we seem to be paving the way to provide something for the patients who have not been able to get satisfactory treatment.
This is a disease where inhaled antibiotics have so far failed because the problem with treating the pulmonary Pseudomonas aeruginosa infections of these patients was that many of them did not tolerate the inhaled antibiotics well.
Q: What does the competitive landscape look like for inhaled antibiotics?
A: There is another company developing a once-daily inhaled antibiotic for cystic fibrosis. They were put on clinical hold so I’m not sure if and when they will be able to proceed. Ours is a different class of antibiotics. Our antibiotic is also a broad-spectrum antibiotic so we actually can go after some of the other bacteria, both gram negative and gram positive bacteria, as opposed to just going specifically after Pseudomonas aeruginosa.
Q: Talk about your tobacco smoking cessation product and how that fits into your product pipeline.
A: The most common cause of respiratory disease is smoking. Smoking causes more healthcare damage than malaria, tuberculosis and HIV put together. In the United States, roughly about 1,200 people a day die from smoking-related diseases.
We suspected that if we emulate the pharmacokinetics of cigarettes, that is, if we deliver nicotine deep in the lungs and it will then absorb quickly into the pulmonary artery which feeds the brain, that it will have a profound impact on the craving for cigarettes. So, that is exactly what we have done. We dissolved nicotine in a small amount of water and put it into a little inhaler that was developed for deep lung delivery. Most of the original investment in this inhaler technology was for pain management — to achieve quick relief of pain — which we developed about a decade ago.
And we found exactly what we suspected: In a single breath, single inhalation of pure nicotine dissolved in water, you can get very rapid entry of the nicotine into the bloodstream and an immediate and sustained impact on craving for cigarettes. So, we are very excited about looking for a partner for this program.
Q: We recently saw the FDA move to control electronic cigarettes. What do you anticipate will be some of your regulatory hurdles in terms of tobacco cessation?
A: We are not sure whether our product will be controlled as a tobacco product, and, therefore will need a very different path to acceptance by the regulatory authorities, or whether the FDA would prefer us to develop it as a prescription product, and, which, initially, a doctor would prescribe it because a lot of these nicotine replacement products eventually become over-the-counter products that do not require prescription.
Q: What are some of your other goals for the next year or two?
A: We’d like to bring Pulmaquin — the inhaled antibiotic — to the patients with bronchiectasis and cystic fibrosis as fast as possible. So, that is what our company is focusing on. And, in the background to that, we are looking for a partner that would be able to do global developing and marketing of the smoking cessation product.
Q: Are you looking for those partnerships now?
A: We are seeking partnerships for the inhaled antibiotic and for smoking cessation. Partnerships bring valuable expertise and resources to the company.
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