Bronchitol: 5% FEV1 improvement with one dose

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GenH

New member
I just thought I would post some information about Bronchitol. Bronchitol has been available in Australia since August so I decided to do the challenge (first dose trial).

I've recently felt that pulmozyme and hypertonic work really well for me, so I was not expecting to find much improvement with Bronchitol. I also knew there was a very common side effect- basically a coughing fit as Bronchitol can irritate your throat/airways- which has stopped several of my friends from continuing to take Bronchitol. I took the challenge and I cleared that much with one dose of Bronchitol that my FEV1 went up 5% (the average in the trial was a relative improvement of 6.5% or about 120ml). My lungs felt good and I had no cough for several days after this dose of Bronchitol. I am starting it properly next week so I am hoping that if Bronchitol continues to work well for me, when well I may only need Kalydeco and Bronchitol. This would mean no nebs! I have written more here http://magicbluepill.wordpress.com/2012/12/06/first-dose-of-bronchitol/

Bronchitol is a new CF medication made from mannitol powder that is taken in a small inhaler. Bronchitol promotes the movement of water into the airway secretions which means the mucus is thinner and easier to clear. This works in a similar way to hypertonic saline, which also thins mucus by promoting osmosis. Bronchitol has been available on the PBS in Australia since August 2012. It has also been approved by the EMA in Europe, but I am not aware of anyone there taking it yet. It is being reviewed by the FDA. There is also a named patient program overseas, I am aware of at least one person in the US who is on this program. I am not sure about the criteria, here is the link: http://www.pharmaxis.com.au/named-patient-program

There is more information about Bronchitol here: http://www.pharmaxis.com.au/bronchitol and http://www.pharmaxis.com.au/bronchitolpi
 
B

bigstar

New member
This seems amazing! Have we talked about this again? I live in Europe but i haven't heard about this being on the market! Anyone else who could possibly share experiences?
 
G

GenH

New member
Bigstar- similar to hypertonic and pulmozyme, some people react to bronchitol and cannot take it, or do not improve much with it. There are others though who do improve significantly. It is nice to have 3 options now, particularly for those who cannot take either pulmozyme or hypertonic saline.

The EMA approved Bronchitol in April 2012, and NICE in the UK approved Bronchitol in Oct 2012. Hopefully this means it will be available in the UK soon. I am not sure about other european countries, I am just going by what is written here http://www.pharmaxis.com.au/bronchitol

I only know of two other first hand accounts, one woman in Australia has improved from FEV1 74% to 84% after 1 month and another woman in Australia wrote this after 2 weeks of Bronchitol:

I have been on 'The Bronch' (as I call it) for 2 weeks now. The first week I did without Pulmozyme to compare and it didn't disappoint! This is what I have experienced so far: My chronic Asthma is gone
. tight chest Gone
. chronic crackles gone
. stopped sybicort (and it's allergy season!)
. my lungs feel very comfortable
. exercise tollerance improved
. got up the last subborn plugs of mucus that Kalydeco had losened
. Don't need my ventolin puffer in during the day
. halved inhaled anti (Tadim)
. stoped needing Hypertonic saline
. feeling better all round
All of these changes are since starting Bronchitol! I am 100% impressed!!!
Please remember I am on Kalydeco too, but Bronchitol has taken it to another level (which I didn't think was possible!). Kalydeco + Bronchitol + Pulmo are my CF trifecta!!!

 
G

GenH

New member
Looks like it wasnt a fluke, I started my one month trial today and I went from 66% to 73%. I'm using the pico1 so this is not as accurate as the hospital, but at the hospital I improved from 65 to 70 so its pretty similar.

I just came across this press release:

02 August 2012

U.S. FDA ACCEPTS BRONCHITOL NEW DRUG APPLICATION FOR REVIEW

Pharmaceutical company Pharmaxis (ASX: PXS) is pleased to announce it has received notification from the United States Food and Drug Administration (FDA) that the New Drug Application (NDA) for its cystic fibrosis product, Bronchitol®, has been accepted for standard review.

The FDA has assigned the Bronchitol application a Prescription Drug User Fee Act (PDUFA) goal date of 18 March, 2013. If the application is approved, Pharmaxis anticipates Bronchitol could be available for US patients with cystic fibrosis in the second quarter of 2013.

Pharmaxis is seeking approval for Bronchitol for the management of cystic fibrosis patients 6 years of age or older to improve pulmonary function. Cystic fibrosis is a disease that affects around 30,000 people in the United States and is the most common life-limiting genetic disease.

The NDA includes results from two Phase III trials, conducted by Pharmaxis, the results of which were presented at the 2011 North American Cystic Fibrosis annual meeting and recently at the 2012 European Cystic Fibrosis Society annual meeting.

Pharmaxis CEO Dr Alan Robertson said, "The Company is pleased that the FDA has accepted the Bronchitol marketing application and we are looking forward to discussions with the FDA as we work to make Bronchitol available to patients in the U.S."

Bronchitol has Orphan Drug Designation in the U.S. and is approved for marketing in Australia and throughout the European Union.

http://www.irasia.com/listco/au/pharmaxis/press/p120802.htm
 
T

triples15

Super Moderator
Very interesting stuff, thanks for posting! I am glad you have seen such an improvement!

I was in the mannitol study here in the states. I saw a small improvement in FEV1 and maintained it throughout the study (save for one exacerbation). It was rather harsh and always set off a coughing fit. However, after the first couple capsules I could finish no problem. I felt pretty good while on it as well.

I hope it is eventually approved here. I would love to have another med to add to our arsenal!!

Take Care,

Autumn 32 w/CF
 
J

JENNYC

New member
Gen does The Bronch take the place of Hypersal pretty much? If Hypersal improved lung function by 5% and The Bronch increases by 5%....does taking away the Hypersal drop it back down 5%? Sorry just a little confused about that. Also are there any other side effects besides the cough due to irritation? This is very interesting! Thank you for sharing with us!!
 
G

GenH

New member
JENNYC said:
Gen does The Bronch take the place of Hypersal pretty much? If Hypersal improved lung function by 5% and The Bronch increases by 5%....does taking away the Hypersal drop it back down 5%? Sorry just a little confused about that. Also are there any other side effects besides the cough due to irritation? This is very interesting! Thank you for sharing with us!!
Click to expand...

Hi Jenny,

Yes basically so far bronchitol is taking the place of pulmozyme- both pulm & bronch give me about 5%, but I have not had both at the same time (bronch may be better long term though and I am about to travel overseas so travelling without a nebuliser and without needing a fridge is much easier).

I sit at about 70% with Pulmozyme, Hypertonic and Kalydeco. If I stop pulm & hypertonic (& now bronchitol) it drops to 65ish. Pulm alone seems to get me back up to about 70 to be honest, I just do the hypertonic hoping its making a slight difference.

Bronchitol alone got me back to 70 with one dose (having not done pulm & hyper for a week). This takes 2 or so days with pulm & hypertonic to get back to 70 after no treatment, so bronchitol is working faster for me. I dont know if Bronchitol will get me higher long term. I think in my case this is unlikely as I am on Kalydeco and have already improved from 41%-71%, I pretty much think I'm close to my max now.

If someone is currently on pulm & hypertonic and adds bronchitol (this would be like me starting at 70 with my old treatment routine), I would imagine there would be a smaller effect, when I am back from overseas (travelling to china with Kalydeco & Bronchitol and no nebuliser, pretty exciting but weird not using one!) I will try this and monitor the different options with my pft machine.

Does that make sense?

Table 1 has a list of the side effects, pretty similar effects to most of our other nebs http://www.pharmaxis.com.au/assets/pdf/BRO026_Bronchitol_AU_PI_1_HR.pdf

Gen
 
G

GenH

New member
It is still going through the FDA, hopefully will be available in the US in quarter 2 next year, see post 4 above. There is a named patient program in the US but I am not sure about the criteria. I know of one person in the US who is on Bronchitol through this program. There are details about this above as well (post 1).
 
J

JENNYC

New member
Thanks for all the info Gen!! And I hope you have a great trip and keep your lung function up!! That is exciting not having to worry about a fridge. :)
 
G

GenH

New member
I finished the 1 month trial two weeks ago and blew 70% FEV1 at clinic. This was an interesting 1 month trial as I was in China, became sick with a cold & subsequent chest infection, was not on pulmozyme or hypertonic and only had Bronchitol and Kalydeco. I think it was a great result, normally I would be much lower after travelling and getting sick. Much of this is due to Kalydeco, but Bronchitol seemed to help keep me at the 70% (I was 70% at 4 weeks post K, 71% at 8 weeks and now 70% at 4 months). I am continuing Bronchitol and Pulmozyme for the time being to see how I go with more normal circumstances! I have decided to stop taking Hypertonic.

I've tried a few options several times over different days to see what combination helps my pfts according to my pico1. Pulmozyme alone gets me to about 70% (65-66 with no treatment), adding either hypertonic or bronchitol gets me a little higher (71-72). Bronchitol alone also seems to get me to about 70%, but hypertonic alone seems to get me to about 67. Given that I am on Kalydeco I'm not sure that I'm a good example, my % results could be smaller as my lungs have already improved significantly.

With the combination of Bronchitol & Pulmozyme, my lungs feel better and I have a less productive cough. I feel better than when on Pulmozyme & Hypertonic.
 
G

GenH

New member
Yes I did see it did not pass the safety and efficacy questions. Here is a statement from Pharmaxis: http://www.afr.com/rw/Wires/Stories/2013-01-31/ASXAnnouncements/PXS_01377531.pdf).

I've read the journal articles that report on the phase 3 studies, one had a statistical significant improvement and the other was at 0.059 (not far off the 0.05 needed for statistical significance). In the study with the 0.059 the bronchitol group improved 106ml and the control group improved 52ml which contributed to the primary end point not being met (the improvement in the control group decreased the statistical significance as there was a smaller difference between the groups). One of the factors that may have influenced this was the control group having a small dose of Bronchitol (I'm guessing for blinding).

---------------

I wrote this on facebook so thought I would copy it here in case anyone is interested

I just looked at the Bronchitol research, there were two large phase 3 trials and one article recently pulled the data together from both of these (http://www.ncbi.nlm.nih.gov/pubmed/23234802). With the data from both trials, overall the mannitol group improved 73ml (relative 3.5%) compared to the control group which is p<0.001 (statistically significant). The mannitol group improved 114ml from their baseline, p<0.001.

When this was broken down into subgroups, it was found that children and adolescents did not have a statistically significant improvement compared to controls, but adults did. However children had a statistically significant improvement compared to their baseline. Adults improved 2.55%, children 3.14% (both absolute % and p<0.05) and adolescents 0.60% (not significant) from their baselines. The article shows confidence intervals, which show the range of 95% of the populations. These show that majority of the children and adolescents improved, but some did not which is why the p values are not as strong.

People taking pulmozme improved 62mls, those not on pulm improved 92mls. People with pseudomonas improved 125ml from baseline (110ml from control).

So overall the results are statistically significant for the adults, with mixed results for the children/adolescents, however majority of the children and adolescents had varied improvements.
 
C

CysticKid

New member
It'll be interesting to see if they pull the children's data from the study pool and try to get just an adult indication.
 
G

GenH

New member
Yes I agree it will be interesting to see what happens- I saw this comment yesterday "The FDA’s Pulmonary-Allergy Drugs Advisory Committee unanimously voted against recommending Pharmaxis’ cystic fibrosis (CF) drug Bronchitol for approval. While committee members were concerned the Bronchitol (dry powder mannitol) was not proven safe and effective in children, most said they would have voted in favor of approval if the indication was only for adults."

http://www.fdanews.com/newsletter/article?articleId=152807&issueId=16512

This was also interesting: Pharmaxis CEO Dr Alan Robertson said, “The Committee vote is disappointing, however, we are aware that these recommendations are not binding on the FDA and we will continue the process of working with the FDA to bring Bronchitol to patients in the US. It is important to remember that we are in a process and that opportunities remain to discuss the issues that were raised by the Committee before the FDA makes its final decision on 18 March 2013.”

http://www.afr.com/rw/Wires/Stories/2013-01-31/ASXAnnouncements/PXS_01377531.pdf
 
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