Refill Rate_How Do We Improve It? Thoughts and Suggestions?

[compound26]

spiro  michaelcastagna

        I am taking the liberty copying Spiro’s posts below to create a new thread to see if we can have some discussions on improving the refill rate.

        "Spiro believes that in order for MNKD's share price to make significant advancement, barring some unexpected positive development not related to Afrezza, it will be necessary for MNKD to meet certain Afrezza sales levels. After studying Sanofi's early launch numbers, Spiro has decided that he would like to see some progress in sales by week 12 of MNKD's launch. At week 12, SNY only had 210 NRX and 257 TRx. It appears that Sanofi was only achieving about a 20% refill rate. Spiro's definition of progress is focused not only only on NRx numbers but mostly on the need to reach 50- 75% or higher refill rates. Spiro believes that Afrezza's new packaging will be likely the key to MNKD reaching and easily beating Sanofi's refill rates. Spiro is very confident that Mike and Matt have the pieces in place and the proper strategy to make Afrezza a successful alternative to injecting.

        Spiro here, just talking to himself out loud and hoping that he is somewhat correct?" Read more: mnkd.proboards.com/user/44/recent#ixzz4HR2DGewZ

        "Spiro's focus is mostly on refills and retention of adapters. If Sanofi had retained 75% of tit's users, they would still be selling the drug now. The only way Afrezza doesn't work great in most people is improper dosage. The new packaging should keep the costs down for the user and provide the ability to increase dosage with larger meals. Clearly Spiro hopes that NRx will be higher than 212. Spiro wants the TRX to be over 500, which would indicate retention of users. Sanofi only had a TRx of 257 which indicated a poor refill rate. If by week 12, the NRx were 1000 and the TRx were 1100, that would be very troubling for Spiro.

        Spiro here, it's all about refills and satisfied new users." Read more: mnkd.proboards.com/user/44/recent#ixzz4HR2G3t6K

I share with Spiro in that I agree the key for Mannkind's success is to improve the refills rate (retention rate). So it appears to me, right now, we have a great product but a less than satisfactory retention rate.   

I believe Sanofi has stated about a drop-out rate of 65% sometime at the beginning of 2016. They also referenced about 20,000 people tried out Afrezza. Additionally, at one point, we were told 45,000 samples of Afrezza were distributed by Sanofi. All of these were pretty good numbers, except for the drop-out rate (or retention rate).

And in Mike's presentation in the ASM, he said that it won't work when you lose 6 or 7 out of 10 patients every month. Mike also said that, had we had good renewal rate, Afrezza's first year sales would have been in the range of $20-40 million (instead of $7 million).

Here is the link to the Mannkind ASM video. vimeo.com/167332167 (Mike's presentation starts at around 22' and ends at around 35'.)

So Mike’s numbers match up with Sanofi’s number in that the drop-out rate is about 65% (or higher, if it the drop-out is 6 or 7 out of 10 every month).

If we look at our scripts count chart, we have reached to around 250-300 weekly refills at round 1/1/2016. Had we had better retention rate, conservatively speaking, our weekly refills probably would be 400/500 right now and we would we have a TRx of around 500/600 (i.e., matching the Sanofi high water Trx with basically zero promotion and minimal NRx).

Besides insurance coverage, prior authorization and reimbursement hurdles (which hurts retention rate), I believe Mannkind (and Sanofi) so far probably have under-estimated the challenges of titrating Afrezza. My impression is that Al and his team may have thought it would be easier for Afrezza users to titrate Afrezza than the with the RAAs. That probably would be  true if new users of Afrezza have had no knowledge of insulin generally and RAAs in particular and how to use them.  The reality is that Afrezza is more difficult to titrate than RAA because it is a paradigm shifting product and, to proper titrate, a user really needs to first de-learn all his/her knowledge about the usage of RAAs.

I am really glad that Mike and his team are taking the right steps and measures to address the retention issue: Mannkind Cares, titration package, the dosing guide, new sample programs are good examples.

My main purpose of this post is to initiate a discussion in this board to see if, in addition to the above measures that Mannkind is taking, whether we have some other ideas or suggestions to help Mannkind/users to make the titration process easier and more like a sure success process.

Here are a few thoughts of mine just to initiate the discussion:

1. If possible, some type of video or animation guide on titration will be great.

Not sure how restrictive FDA is on this or how difficult it will be Mannkind to produce some type of video or animation titration guide, but I would think if it is possible it would really helpful.

Mike B. at Austrialia produced a few impressive videos (afrezzadownunder.com/afrezza-insulin/) and are really informative. I do not how many Afrezza users have benefited from it, but here is one comment from them:

My son has more stable blood sugars with Afrezza and Tresiba than he did with OmniPod and Humalog. It reduces highs more quickly and eliminates lows. His A1C had been running 7.0-7.2 and declined to 6.6 after two months on Afrezza. It requires a different mindset, but we learned a lot by watching videos at AfrezzaDownUnder.com. The learning curve was a tough week to two, but was greatly aided by our CGM (Mike is right that CGMs are an idea partner to frezza). Son's quality of life much improved. I can be more specific on any particular aspect if you are more curious. We absolutely love Afrezza.

www.tudiabetes.org/forum/t/exciting-news-since-switching-to-tresiba/54986/42?u=charles5

2. If there a way for pull the expertise of the really successful Afrezza uers together and put them to use (like setting up an Afrezza user community)?

Even among our most successful Afrezza users, I noticed that there are a few of them who basically mastered the timing and dosage of Afrezza to a higher level than the others (as evidenced by their CGM graphs with smooth and flat lines). Afrezza Guy is one of them (see his CGM graph below). I would think Matt B. is another one due to the knowledge he demonstrated in his writings on Afrezza on his blog.  Duck Fiabetes NorCal probably is another one (see his CGM graph below. But some may think he may have allowed his BG level to go down too much sometimes).  Gustavo Basualdo may be another user that has excellent controls of his blood sugar level.

To this end, we will look at purely how well an Afrezza user is able to use Afrezza to control his blood sugar level regardless whether he/she is well known to the others in the diabetic community. We really need to pool these users and compile their most helpful tips and find ways to share the tips to the new users.

I try to the extent I can to compile the useful tips in afrezzajustbreathe.com. However, I do not think the site generates a large traffic to be helpful to a lot Afrezza users.

www.afrezzajustbreathe.com/tips-from-afrezza-users/

I think to a large extent, as a community, we already have a good amount of helpful information (as evidenced by Matt B's site, my above blog post, Afrezzauser's blog (afrezzauser.com/afrezza-journey/), many posts on Twitter and tudiabetes.org). However, most new Afrezza users do not know that such information is out there or, if they do, where to get such information.

I recall Matt mentioned something about Afrezza Advocate Counsel earlier this year. Not sure if Mannkind is still working on this idea.

3. Timing of taking Afrezza

I believe it is now pretty clearly demonstrated that Afrezza is most effective for most meals to be taken 10-15 minutes after the start of the meal. However, I understand that Afrezza’s label is still limiting the manual to say that Afrezza is to be taken “at the beginning of” each meal. There needs to be ways to let users know that, in this case, “at the beginning of” each meal actually should be translated as 10-15 minutes after the start of the meal.

afrezzadownunder.com/2015/10/afrezza-timing-is-everything/

www.afrezzajustbreathe.com/tips-from-afrezza-users/

4. Dosage of Afrezza

Matt B. has demonstrated that it is best to think Afrezza dosage as small, medium and large rather than 4, 8 or 12 units as he think it is a bit misleading to covert the units between Afrezza and RAAs. Also, he demonstrated it needs more Afrezza to bring blood sugar levels down (once it is up there) than to keep the blood sugar level from rising in the first place. I understand that Afrezza’s label is still limiting the manual to say these things, but finding a way to bring such information to the users will definitely help users to titrate (so that they will pay more attention to the timing of the Afrezza, not afraid of taking large dosage of Afrezza and remember to take follow-up dosage).

afrezzadownunder.com/2015/09/afrezza-units-insulincarb-ratios/

5. Follow up dosage(s)

I understand for users of RAAs, you generally do not take any follow-up dosage as that will have an insulin stacking issue. However, contrary to that of RAA, due to its short tail, not only it is much much safer to take follow-up dosage of Afrezza (with little risk of insulin stacking), it actually is often necessary to take follow-up dosage of Afrezza in order to obtain optimum control of one’s blood sugar level. How do we best bring this information to the new users of Afrezza.

www.afrezzajustbreathe.com/tips-from-afrezza-users/

[compound26]

michaelcastagna Not sure if someone at Mannkind can arrange for a new interview done at Tudiabetes.org. A few happy users of Afrezza post there from time to time. But apparently, the vast majority of the users there have little or no knowledge of the existence or benefits of Afrezza.

Sam (Afrezzauser) did one last year. But that was over a year ago. Sam Finta, “AfrezzaUser” Talks About Inhalable Insuline

[mnkdnut]

Good post, CP26!! I'm in total agreement that Sanofi's biggest failure was not diagnosing and fixing the problem of patient retention. This is a classic case of most patients needing coaching and support to get through those first critical weeks before it really clicks for them. I don't think the early prescribers knew what to do in this regard either. My first choice would be a nurse-staffed hotline that patients could call to get advice. However, the cost of that may be an issue for MNKD, and MNKD nurses may be too handcuffed by the label to say what they really need to say. Second choice would be an online forum where experienced patients could offer the benefit of their own experience to new patients. Perhaps MNKD could provide a grant to some Diabetes organization to get the ball rolling. People like Sam and Eric would make great moderators. I'd also make sure that part of what the MNKD nurse educators and reps do is set expectations with doctors that patients will need help figuring out proper dosing/timing, and that they should have that conversation with patients. Patients should also be informed about any support resources available to them and be encouraged to use them.

[sayhey24]

Assuming 2000 prescribing endos if each one wrote 1 new script a week and 20% were retained that would be over 20,000 retained afrezza users per year.  I think SNY's first problem was they never launched the product.  I think the second problem was insurance coverage.  What T2 is going to spend $300 a month when prior they were paying pennies for metformin.  Insurance coverage was key and SNY failed to meet.  MNKD has switched gears and is now targeting CGM T1's and current insulin dependent T2's.  It seems after a couple of weeks the CGM T1's can dial it in pretty well.  For the T2's this may be a little more interesting depending on how they are currently being treated.  For those not using a CGM it would be nice if they could borrow one for 2 months to dial it in.  Maybe MNKD can work out a deal with Dexcom and rent or loan these new users one for a couple of months.

[compound26]

In the label change that Mannkind is planning to submit to FDA in Sept./Oct., I wonder if they can get both of the following reclassification and clarification:

1.  Ultra-rapid classification. 

Whether Afrezza can be classified as ultra-rapid insulin (a class by itself) as compared with within the same class with RAAs;

2.  Dosing time clarification.

Whether the instruction can clarify that Afrezza is to be taken "after the start of" the meal instead of "at the beginning of” each meal.  

"At the beginning of” each meal implies that you first take the Afrezza and then you eat.

"After the start of" the meal will be much clear. You first eat (and start the meal) and then you take the Afrezza.  

While there may only be 10-15 minutes difference of timing between these two dosage time, this difference can be crucial for users to get the best results with Afrezza.

[esstan2001]

I prefer

...recommended dosing within 15 minutes after the start of the meal.

then something to the effect of 

... Supplemental doses to cover [verbage describing slow to metabolize foods] as required

[compound26]

esstan2001  Agree with your wording. It will be great if the label can be worded like this. To me, the more specific the better. People generally just follow directions when take a medicine. Since Afrezza is no new (and so different from the RAAs), a specific instruction (with the optimal timing of the dose) will probably bring out the best results with most new users upon their initial trials.

I will probably add a little bit:

...recommended dosing within 15 minutes after the start of the meal (which timing may be fine tuned as necessary ......).

then something to the effect of

... Supplemental doses to cover [verbage describing slow to metabolize foods] as required

[peppy]

trying to think it through, I am wondering if giving a beginners blood glucose check guide may help.

those that do not have a continuous glucose monitor may find it most helpful the first week to check your blood glucose levels:

AND Then suggest times most helpful to assess whether they took enough units and/or may need a follow up dose.

something like for the first week check your blood glucose before eating.

calculate if you need a 4u small meal, 8u medium meal or 12 u large meal dose.

check your blood sugar again in 45 mins?  an hour? 

One more thing compound, did matt in one of his video's suggest a 45 min time on a follow up dose? at a long meal because he calculated the window well?

Pep

People with out continuous glucose monitors, efficacy will probably be judged through Hga1c?

The tighter the control post meal the better?

[agedhippie]

Aug 16, 2016 7:19:39 GMT -5 peppy said:

trying to think it through, I am wondering if giving a beginners blood glucose check guide may help.

those that do not have a continuous glucose monitor may find it most helpful the first week to check your blood glucose levels:

AND Then suggest times most helpful to assess whether they took enough units and/or may need a follow up dose.

something like for the first week check your blood glucose before eating.

calculate if you need a 4u small meal, 8u medium meal or 12 large meal dose.

check your blood sugar again in 45 mins?  an hour? 

One more thing compound, did matt in one of his video's suggest a 45 min time on a follow up dose? at a long meal because he calculated the window well?

Pep

People with out continuous glucose monitors, efficacy will probably be judged through Hga1c?

The tighter the control post meal the better?

How to use Afrezza without a CGM is critical as less than 10% of Type 1 diabetics have a CGM and almost nobody on Medicare has one. That's without discounting the number who have one but never use it.

Telling people to retest after 45 minutes is not going to be popular, the likely outcome is that they will not retest (you are meant to test 2 hours after eating today but I don't know anyone who does) so plan for that to fail.

I would not bother about retention numbers after 12 weeks. People will get a 180 cartridge pack initially which will probably last 6 weeks then they will need a new prescription for their normal dose, then 3 months later they will renew. The key times will be the transition from titration to regular use, and the first renewal of the regular prescription. I am not sure if those show as NRx or TRx though.

The key thing to remember is that the early adopters were prepared to put in a lot more work and work through more issues than typical diabetics will be. You are asking people to forget everything they know about something that they understand which keeps them alive day to day - that's a big ask. Handling that jump sensitively will be critical to success - the first thing that a diabetic learns is that what works for one person often will not work for another.

[wiscdh]

How do we reach out to the people who have tried Afrezza but then stopped using it? If Sanofi's numbers are correct and 20,000 people have tried Afrezza and the drop out rate was 65%, that means there are about 13,000 people who, for whatever reason, stopped using Afrezza. How do we reach out to these people? What were their reasons for not continuing on Afrezza? How can we get them back?

[promann]

Aug 16, 2016 8:18:10 GMT -5 wiscdh said:

How do we reach out to the people who have tried Afrezza but then stopped using it? If Sanofi's numbers are correct and 20,000 people have tried Afrezza and the drop out rate was 65%, that means there are about 13,000 people who, for whatever reason, stopped using Afrezza. How do we reach out to these people? What were their reasons for not continuing on Afrezza? How can we get them back?

 We can not get their names because of privacy issues but I agree to try to reach out to them and help them to understand how to properly use it, and its benifits.

[agedhippie]

Aug 16, 2016 8:27:02 GMT -5 promann said:

Aug 16, 2016 8:18:10 GMT -5 wiscdh said:

How do we reach out to the people who have tried Afrezza but then stopped using it? If Sanofi's numbers are correct and 20,000 people have tried Afrezza and the drop out rate was 65%, that means there are about 13,000 people who, for whatever reason, stopped using Afrezza. How do we reach out to these people? What were their reasons for not continuing on Afrezza? How can we get them back?

 We can not get their names because of privacy issues but I agree to try to reach out to them and help them to understand how to properly use it, and its benifits.

HIPAA prevents this. However I believe Sanofi had stats on why people stopped and under the terms of the partnership that should now be passed to Mannkind.

[mannmade]

Another consideration which makes it harder to get a previous drop out to try again vs aquiring new users imho is that the user experience is very personal to the individual diabetic patient for a variety of reasons, such as emotional state, T1 v T2, lifestyle, etc...

And in addition to the issues of each individual there is the proximate cause of each patient's reason for discontinuing such as: price, insurance, cough, etc...

So once they have tried and failed in their minds they may be very hesitant to return. At a minimum it may require extra time and attention to each individual who dropped out (again mho) since their personal experience was not good the first time.

So how do you reach each individual?

And as I used to tell my staff of 35 it is much easier to keep a client happy than it is to try and win them back.

[sayhey24]

If they all had CGMs which were connected to the cloud and they were remotely monitored, this would be a huge help.  I had a long talk with Mike about this.  For those not using a CGM if they tested 90 minutes after meals in addition to morning and night and entered it into a web app for remote monitoring this would do it too.  I think the Vdex model is what they need to get up and going to solve the question you raise.  Both Verily and IBM are working towards this remote monitoring service in addition to what Vdex announced.  Maybe a more lightweight solution like the San Meditech approach is all MNKD needs to jump afrezza and get the remote monitoring to improve retention.  I suspect a CGM loaner program for T2s for about 2 months is all the T2s would need with the CGM.  After that manual testing would probably do it.  Then again if San Meditech could get US approval and the CGM price into the $50-100 range a lot more T1 and T2s would own them.

[peppy]

Aug 16, 2016 17:52:47 GMT -5 sayhey24 said:

If they all had CGMs which were connected to the cloud and they were remotely monitored, this would be a huge help.  I had a long talk with Mike about this.  For those not using a CGM if they tested 90 minutes after meals in addition to morning and night and entered it into a web app for remote monitoring this would do it too.  I think the Vdex model is what they need to get up and going to solve the question you raise.  Both Verily and IBM are working towards this remote monitoring service in addition to what Vdex announced.  Maybe a more lightweight solution like the San Meditech approach is all MNKD needs to jump afrezza and get the remote monitoring to improve retention.  I suspect a CGM loaner program for T2s for about 2 months is all the T2s would need with the CGM.  After that manual testing would probably do it.  Then again if San Meditech could get US approval and the CGM price into the $50-100 range a lot more T1 and T2s would own them.

agreed.

I hadn't heard about "if San Meditech could get US approval ". do you have more information?

I am still watching glucowise for distribution. nothing yet.

What is the current status? When will it be available to order?GlucoWise™ is currently in development and will be available to purchase once clinical trials are completed. We expect to start taking pre-orders in late 2016.

www.gluco-wise.com/