APL-130277 still without FDA Approval: Why?

[sharoncrayn]

Apomorphine is a somewhat strange Dopamine Agonist (non-egoline DA Parky B!) that required subcutaneous injections. It certainly hasn't been a mainline DA prescription in the USA.

Sunovian developed back in 2012 a 2 part sublingual film that was applied under the tongue to reduce the difficulties of injection (and the resulting pain). They moved their new method and its application all the way up the chain of of CTs (Phase 1,2, and 3) eventually asking for FDA approval way back in 2018.

Apokyn's Apomorphine's approval by the FDA goes all the way back to 2004. So you would think the sublingual film would get a fast track, no problem approval. The FDA rejected their application in early 2019.

I don't understand the FDA's rejection and call for "more information". I surmise the FDA wanted information about whether or not the film was inferior/superior to the injection approach and why. Sunovian has not examined that issue probably for obvious reasons. Second, the number of different doses (6) and frequency of use (as many as 5 in 1 day) probably raised additional questions. Perhaps too many combinations. Third, The traditional application methodology raises some serious questions about this drug's bioavailability although the trial results were very encouraging.

Even with these concerns which are legitimate, APL-130277 clearly showed efficacy in reducing "off" periods in PD patients who had progressed to at least one "off" period of a significant duration and were using a significant amount of a L-Dopa drug. To me, the FDA seems a trifle too conservative on this application.

[Jebbie12]

I was also disappointed by the FDAs rejection. Still hoping. I use apokyn, but would welcome a sublingual over an injection

[sharoncrayn in reply to Jebbie12]

Jeb:

This dopamine agonist (APO) is not typically prescribed in the US, so I wonder why your physician decided to prescribe it for you. Much more frequently used in the EU and UK/Australia.

Even with the use of an infusion pump (which bypasses the GI tract) the typical length of time on this drug is relatively limited to a few years. Published in the IM Journal, the Aussie study found APO infusion was successful in reducing L-Dopa and other DAs (which is of course the primary focus of infusion APO, which somehow is different than what Sunovian says about the sublingual film APO).

However, The study found that after 2+ years, 2/3s of the participants had "intolerable side effects" and stopped the treatment. In contrast, the TOLEDO III TRIAL reported very positive results, especially in decreasing "OFF" time. The problem with this trial? Only 12 weeks in duration.

Would or does the sublingual protocol alleviate this issue of "longevity"? The CT Phase 3 by Sunovian was also simply too short to assess this issue adequately.

Monitor your side effects closely and work constantly with your physician. If necessary, consult with a PD Center of Excellence.

S

[matthias_baum]

Hello sharoncrayn,

I Am using apomoŕphine s. c. since 3 years! without any relevant progression or side effects. The Applikation via s,c, infusion is NOT easý, but compared with the L- Dopa infusioc can be followeď by peritonitis and death (30% on the long run). I have parkinson since 16 years with high muscle tension and early dystonia of the big toes. No Tresor. Both Symptoms are influencrd quite well. Thè use of apomoŕphine is NOT so widespread, as senseful and necessarý.

[sharoncrayn in reply to matthias_baum]

Matt:

Don't think you mean infusion (into your vein! or with an IV); most commonly SC is done by injection (under the skin).

I wrote a post about the APO sublingual film that Sunovian has been trying to get approved by the FDA. I used the numerical name for it, so I forget the actual title, but I referenced APL-130277 in the title.

In my perspective, Sunovian have been pushing the film (CT Phase 3 has been completed) due to the difficulties with the subcutaneous injection (or the use of a pump) for most people.

Did your EU physician prescribe "domperidone", a D2 Dopamine agonist, along with APO? Usually given a couple of hours before treatment with APO (reduces nausea and vomiting).

What is your dose? (10mg/mL)? Do you take L-Dopa at the time of APO SC infusion?

Haven't heard too much about L-Dopa (INTESTINAL!) infusion except in studies or CTs. On balance, the continuous infusion of L-Dopa was deemed positive.

Anyway, glad to hear it is working for you.

S

[matthias_baum in reply to sharoncrayn]

Ok, habe some ösophagitis, no Problem (und 100mg omeprazol3xa,month). Furtermore Therme my Earl dysztona