levodopa prodrug (XP21279) / Azurity Pharma - LARVOL DELTA

Parkinson Disease: Managing Off-Episodes - Episode 9: Parkinson Disease Medications and Alternate Courses of Therapy (NeurologyLive) - "Rajesh Pahwa, MD: Some of our patients have OFF episodes randomly during the day or may not have them as often. And on-demand therapy or as-needed therapy are other decent options we have. Right now, we have 3 different options, and the other advantage about on-demand therapies is that it bypasses the gut, so we know that it is going to work, and it also works faster than the oral preparations."

Video

Parkinson Disease: Managing Off-Episodes - Episode 10: Unmet Needs and Key Takeaways for Treating Parkinson Off-Episodes (NeurologyLive) - "Rajesh Pahwa, MD: It's so true. We can treat both motor fluctuations and dyskinesias better than we could do even 20 years ago. But you're right, we do have some exciting products in the future. You talked about the subcutaneous options. Apomorphine right now, it's as-needed therapy, but in Europe apomorphine subcutaneous infusions have been around for decades, and it is time we may have it in the United States, where we could use it to give them continuous benefit during the day."

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Treating Morning OFF Episodes in Parkinson’s Disease - Episode 6: Practical Advice for Managing Morning OFF Episodes in Parkinson Disease (NeurologyLive) - "Peter A. LeWitt, MD: In my clinical practice and experience with all 3 on-demand products, that is inhaled levodopa for pulmonary uptake, apomorphine given by subcutaneous injection in liquid form, or apomorphine given in strips that are absorbed through the mucosa under the tongue, each of these has a role to play for certain patients. I use all 3 of them, and some of my patients have tried more than 1 of them. It's hard to know which will work best for every patient. Some patients may have adverse effects, such as lowering of blood pressure or nausea, with apomorphine no matter how you deliver it. For others, inhaling levodopa will have enough throat irritation or coughing that they choose not to continue with this drug. And apomorphine as a drug is probably more potent than levodopa in the doses that are used as on-demand therapies."

Video

Treating Morning OFF Episodes in Parkinson’s Disease - Episode 5: Parkinson Disease: SL Apomorphine Hydrochloride for Morning OFF Episodes (NeurologyLive) - "Peter A. LeWitt, MD: Apomorphine is a dopaminergic agonist that, in addition to being given subcutaneously, can also be given sublingually in a strip that is rapidly absorbed through the mucosa of the mouth and going into the circulation to treat Parkinsonian symptoms. Like the injected form, apomorphine has an optimal dose for many patients, and several different dose strips are available so that a patient can determine for themselves whether adverse effects would occur or whether they get optimal effect. Patients typically are asked to start with the lowest dose and build up gradually in repeated trials as to whether a particular dose is giving them the effect they want without adverse effects."

Video

Wearable Vibration Device May Ease Parkinson’s Tremor - "Dr. Michele Tagliati...'Tremor in Parkinson's disease is an interesting symptom, but it is often not the most disabling symptom,' he said....'We don't have perfect control of tremors, so a noninvasive method would be really nice,' Tagliati said. But it's too early to say whether this device will fill this need. 'More study is needed before any conclusions can be drawn about this wearable device,' he added."

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Treating Morning OFF Episodes in Parkinson’s Disease - Episode 4: Parkinson Disease: SQ Apomorphine Hydrochloride for Morning OFF Episodes (NeurologyLive) - "Peter A. LeWitt, MD: Another option for treating, on demand, the need for getting dopaminergic effect for rescuing a patient from an OFF state is injected apomorphine or apomorphine hydrochloride, which is available in liquid form and an injector that the patient can choose to give up to several times per day. Patients who are started on this therapy are titrated to an effective dose and to get to know it, both from the point of view of its benefits and adverse effects. This medication has been available for many years. It's the first on-demand therapy and can augment the effect of levodopa or other dopaminergic drugs because apomorphine, although it's a synthetic compound as far as the brain is concerned, is a very effective dopaminergic drug. And patients who are injecting this drug get a blood level rapidly, and usually within 10 to 15 minutes can experience a recovery from an OFF state to an ON state."

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Treating Morning OFF Episodes in Parkinson’s Disease - Episode 3: Parkinson Disease: Levodopa Inhalation Powder for Morning OFF Episodes (NeurologyLive) - "Peter A. LeWitt, MD: One option for rapid treatment of OFF time would be to use levodopa in a micropowder form which can be inhaled through the lungs. The alveoli can take up the powdered form of levodopa and put it into the bloodstream more rapidly than the same drug is absorbed orally in tablet form. The advantage here is the efficiency in terms of timing and the likelihood that that inhaled dose will reach a typical bloodstream concentration that is used on top of what was left over from that last levodopa tablet in order to boost the total blood level of levodopa to a therapeutic range. And this can be used by a patient on demand when observing an OFF time starting to happen, and the patient can use it to get back ON in a reliable manner. This can be used up to several times per day."

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Treating Morning OFF Episodes in Parkinson’s Disease - Episode 1: Challenges With Morning OFF Episodes in Parkinson Disease (NeurologyLive) - "Peter A. LeWitt, MD: Motor fluctuations are a common problem in Parkinson disease after patients have been treated with levodopa for a few years, sometimes as little as 1 or 2 years but generally 3 or more years. Motor fluctuations can be categorized in various ways, including delays in onset of medication benefit, a short duration of each dose of levodopa, perhaps only 2 or 3 hours. Sometimes the unpredictability of absorption or whether a particular dose will go to work for that patient is what characterizes motor fluctuations, and there are other phenomena as well."

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Treating Morning OFF Episodes in Parkinson’s Disease - Episode 2: The Advent of On-Demand Therapies in Parkinson Disease (NeurologyLive) - "Peter A. LeWitt, MD: With regard to managing Parkinson disease, we now have the opportunity to take care of morning OFF episodes. We have therapy available that can do better than just oral immediate-release levodopa. Among those options are what we can call on-demand treatments, medications that can be used at any time of the day but especially first thing in the morning to get a patient back into an ON state from the overnight OFF state that they have because of not taking medication for many hours since the evening before."

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Episode 5: Apomorphine Subcutaneous Injection: Circle of Care Program for Off-Episodes in Parkinson Disease (NeurologyLive) - "Daniel E. Kremens, MD, JD: We've talked about some of the advantages and great results we've had with this drug [apomorphine hydrochloride], but it's not for everybody. There are disadvantages. I know many of my patients are reluctant to use needles. There is also a societal stigma that surrounds needle use as well, and I find that to be a challenge for a lot of patients. It's not necessarily the physical use of the needle...Rajeev Kumar, MD: I agree with that. It's interesting. I call that needlephobia. It's very interesting. When I've talked to many neurologists and patients, if the concept of using a needle is approached in the correct way, then it's amazing how accepting the vast majority of patients are of using a needle to get back on again-when it improves quality of life. It's a very easy thing to administer, and it's not so scary once you've tried it."

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Parkinson’s Drug Levodopa Eyed as Treatment for Severe Macular Degeneration (Drugs.com) - "Dr. Raj Maturi, clinical spokesman for the American Academy of Ophthalmology, said confirming the drug's safety and effectiveness will require a larger, more robust clinical trial. Maturi also expressed concern about potential side effects of levodopa, especially given the age of the population that is affected by macular degeneration. 'You're talking about a population of their 70s and 80s-they already have other things going on,' Maturi said. 'An additional oral systemic drug that they will take for the rest of their life can significantly affect their quality of life. I'm always concerned about the side effect profiles of oral drugs that have to be taken for a long period of time.'"

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Singer Rob de Nijs: "Life doesn't end with Parkinson's" [Google translation] - "Bloem explains that the disease process has been going on for years before the first symptoms reveal themselves and then continues. 'In the brain stem is the so-called black area that produces dopamine, a substance that affects our mood, our ability to plan and organize, but also on movement. In Parkinson's disease, that area is damaged and dopamine deficiency occurs. At a later stage, other areas of the brain may also deteriorate. It is a complex disease, which can involve both physical and mental limitations.'"

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Keeping Treatment Response "On" in Parkinson Disease (NeurologyLive) - "In a recent Viewpoint column in JAMA Neurology, Jorik Nonnekes, MD, PhD...suggested that freezing of gait (FOG) might also be a manifestation of levodopa treatment and a reflection of the peak and valley levels from traditional levodopa regimens. 'It is accepted that long-term levodopa treatment, possibly because of its pulsatile administration, results in loss of compensatory postsynaptic dopaminergic receptor upregulation and maladaptive plasticity of the striatum via influence on physiological forms of synaptic plasticity,' Nonnekes...wrote."

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Five Off Road grants for researchers Radboudumc [Google translation] (Radboudumc) - "12 February 2020...Jorik Nonnekes...received an Off Road grant of €100,000 from ZonMw....'The drug levodopa may play a double role in this,' says Jorik Nonnekes....Nonnekes will now investigate whether long-term use of levodopa actually contributes to the onset of freezing of walking. For this he compares data from Tanzania with the Netherlands."

Grant • Media quote

No longer stay awake during deep brain stimulation [Google translation] (University of Amsterdam) - De Bie: 'We start with medicine. The most commonly used is l-dopa, which was last year shown to be safely used at an early stage of the disease. As the patient gets older and more symptoms or side effects worsen, then DBS is an option. I estimate that five percent of patients are eligible.'

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New Advances in the Treatment of Levodopa-Induced Dyskinesia in Parkinson's Disease (PRIME Education) - "Join in as expert faculty discuss the latest advances in assessing and managing levodopa-induced dyskinesia in Parkinson's disease. They will share key insights on integrating the latest evidence as well as strategies for incorporating patient-centered and coordinated care into clinical practice. Learn more about: Effectively identifying dyskinesia and assessing the burden of dyskinesia on patients' quality of life, physical functioning, and degree of disability....Optimization of care through the engagement and collaboration of patients, caregivers, and multidisciplinary teams."

CME

Altering Oral PD Regimens Versus Using On-Demand Therapy (NeurologyLive) - "I mentioned the different roles of tinkering with meditation or the experiments we can do to help a patient adjust medication to the best effect. I think the decision of whether to alter oral drugs, levodopa being the short-acting agent, but also to add longer-acting therapies, such as dopaminergic agonists, represents one way of handling motor fluctuations, especially the kind that can have an intermingling of delayed ON episodes and the wearing OFF episodes."

Video • Parkinson's Disease

XenoPort announces XP21279 phase 2 clinical trial results in patients with advanced Parkinson's disease (Market Watch) - P2, N=35; 279/CD dosed three times per day reduced mean daily “off time” by 46% compared to baseline when the patients were taking their pre-trial Sinemet dosing regimen; In the primary analysis of the trial, the improvement with 279/CD was not statistically better than the improvement seen with optimized Sinemet dosed four or five times per day during the double-blind phase of the trial

P2 data • Parkinson's Disease

Double-blind study of an actively-transported levodopa prodrug, XPc, in Parkinson disease (AAN 2013) - Presentation time: Tuesday, March 19, 2013 7:30 AM; P2, N=35; NCT01171313; "XP21279-CD 3 times/day reduced variability in LD concentrations compared to LD-CD 4 or 5 times/day, supporting the advantage of the novel prodrug delivery of LD. The efficacy and tolerability results suggest that more extensive studies are warranted."

P2 data • Parkinson's Disease

Double-blind study of the actively transported levodopa prodrug XP21279 in Parkinson's disease (Mov Disord) - P2, N=35; Sponsor: XenoPort; NCT01171313; "Both treatments had a similar incidence of new or worsening dyskinesias. XP21279-carbidopa administered three times daily produced a reduction in off time similar to that of carbidopa-levodopa administered four or five times daily, and the difference was not statistically significant. XP21279-carbidopa significantly reduced variability in levodopa concentrations compared with carbidopa-levodopa."

P2 data • Parkinson's Disease

Actively transported levodopa prodrug XP21279: A study in patients with Parkinson disease who experience motor fluctuations (Clin Neuropharmacol) - P1/2, N=14; NCT00914602; XP21279 provided less variability in LD concentration compared with CD-LD (p<0.05) in 10 PD subjects with motor fluctuations, consistent with lower peak-to-trough fluctuation for XP21279; Patterns of percentage of subjects OFF were consistent with LD concentration-time profiles for each respective treatment; Compared with CD-LD treatment, 6 of 10 study completers experienced reduction of 30% or greater in average daily OFF time during the last 4 days in XP21279 treatment period

P1/2 data • Parkinson's Disease

Xenoport: Credit Suisse Global Healthcare Conference (Xenoport) - Anticipated composition of matter patent expiry in 2025; Anticipated formulation patent expiry in 2030

Anticipated patent expiry • Parkinson's Disease

Xenoport: Investor Presentation (Xenoport) - "XP21279 Phase 2 Study in Advanced Parkinson's Patients"; "Minimal Fluctuation in Levodopa Blood Levels"; "Achieved levodopa levels with XP21279/Carbidopa tablet within the target therapeutic window"

P2 data • Parkinson's Disease

Xenoport: Annual Report 2013 (Xenoport) - Anticipated composition of matter patent expiry in US in 2025; Anticipated formulation patent expiry in US in 2025

Anticipated patent expiry • Parkinson's Disease

Xenoport: Annual Report 2015 (Xenoport) - Anticipated expiry of composition of matter and formulation patent in US in 2025

Anticipated patent expiry • Parkinson's Disease