Tagged: FDA

Nilotinib: the other phase II trial

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In October 2015, researchers from Georgetown University announced the results of a small clinical trial that got the Parkinson’s community very excited. The study involved a cancer drug called Nilotinib, and the results were rather spectacular.

What happened next, however, was a bizarre sequence of disagreements over exactly what should happen next and who should be taking the drug forward. This caused delays to subsequent clinical trials and confusion for the entire Parkinson’s community who were so keenly awaiting fresh news about the drug.

Earlier this year, Georgetown University announced their own follow up phase II clinical trial and this week a second phase II clinical trial funded by a group led by the Michael J Fox foundation was initiated.

In todays post we will look at what Nilotinib is, how it apparently works for Parkinson’s disease, what is planned with the new trial, and how it differs from the  ongoing Georgetown Phase II trial.


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The FDA. Source: Vaporb2b

This week the U.S. Food and Drug Administration (FDA) has given approval for a multi-centre, double-blind, randomised, placebo-controlled Phase IIa clinical trial to be conducted, testing the safety and tolerability of Nilotinib (Tasigna) in Parkinson’s disease.

This is exciting and welcomed news.

What is Nilotinib?

Nilotinib (pronounced ‘nil-ot-in-ib’ and also known by its brand name Tasigna) is a small-molecule tyrosine kinase inhibitor, that has been approved for the treatment of imatinib-resistant chronic myelogenous leukemia (CML).

What does any that mean?

Basically, it is the drug that is used to treat a type of blood cancer (leukemia) when the other drugs have failed. It was approved for treating this cancer by the FDA in 2007.

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DBS2.0: Look mum, no electrodes!

DBS


Deep brain stimulation is a surgical procedure that can provide immediate motor-related benefits to people with Parkinson’s disease.

The approach involves placing electrodes deep inside the brain. This procedure requires invasive surgery and there are no guarantees that it will actually work for everybody.

Recently, researchers at MIT have devised a new technique that could one day allow for a new kind of deep brain stimulation – one without the electrodes and surgery.

In today’s post we will review the science behind deep brain stimulation and the research leading to non-invasive deep brain stimulation.


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Source: Youtube

In 2002, deep brain stimulation (or DBS) was granted approval for the treatment of Parkinson’s disease by the US Food and Drug Administration (FDA). The historical starting point for this technology, however, dates quite far back…

Further back than many of you may be thinking actually…

In his text “Compositiones medicamentorum” (46 AD), Scribonius Largo, head physician of the Roman emperor Claudius, first suggested using pulses of electricity to treat afflictions of the mind.

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Roman emperor Claudius. Source: Travelwithme

He proposed that the application of the electric ray (Torpedo nobiliana) on to the cranium could be a beneficial remedy for headaches (and no, I’m not kidding here – this was high tech at the time!).

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Torpedo nobiliana. Source: Wikipedia

These Atlantic fish are known to be very capable of producing an electric discharge (approximately 200 volts). The shock is quite severe and painful – the fish get their name from the Latin “torpere,” meaning to be stiffened or paralysed, referring specifically to the response of those who try to pick these fish up – but the shock is not fatal.

Now, whether Largo was ever actually allowed to apply this treatment to the august ruler is unknown, and beyond the point. What matters here is that physicians have been considering and using this approach for a long time. And more recently, the application of it has become more refined.

What is deep brain stimulation?

The modern version of deep brain stimulation is a surgical procedure in which electrodes are implanted into the brain. It is used to treat a variety of debilitating symptoms, particularly those associated with Parkinson’s disease, such as tremor, rigidity, and walking problems.

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New drug approved for ALS

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The Federal Drug Administration (FDA) in the USA has approved the first drug in 22 years for treating the neurodegenerative condition of Amyotrophic lateral sclerosis (ALS).

The drug is called Edaravone, and it is only the second drug approved for ALS.

In today’s post we’ll discuss what this announcement could mean for Parkinson’s disease.


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Lou Gehrig. Source: NBC

In 1969, Henry Louis “Lou” Gehrig was voted the greatest first baseman of all time by the Baseball Writers’ Association. He played 17 seasons with the New York Yankees, having signed with his hometown team in 1923.

For 56 years, he held the record for the most consecutive games played (2,130), and he was only prevented from continuing that streak when he voluntarily took himself out of the team lineup on the 2nd May, 1939, after his ability to play became hampered by the disease that now often bears his name. A little more than a month later he retired, and a little less than two years later he passed away.

Amyotrophic lateral sclerosis (or ALS), also known as Lou Gehrig’s disease and motor neuron disease, is a neurodegenerative condition in which the neurons that control voluntary muscle movement die. The condition affects 2 people in every 100,000 each year, and those individuals have an average survival time of two to four years.

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ALS in a nutshell. Source: Walkforals

In addition to Lou Gehrig, you may have heard of ALS via the ‘Ice bucket challenge‘ (see image in the banner of this post). In August 2014, an online video challenge went viral.

By July 2015, the ice bucket campaign had raised an amazing $115 million for the ALS Association.

Another reason you may have heard of ALS is that theoretical physicist, Prof Stephen Hawking also has the condition:

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Source: BBC

He was diagnosed with in a very rare early-onset, slow-progressing form of ALS in 1963 (at age 21) that has gradually left him wheel chair bound.

This is very interesting, but what does it have to do with Parkinson’s disease?

Individuals affected by ALS are generally treated with a drug called Riluzole (brand names Rilutek or Teglutik). Approved in December of 1995 by the FDA, this drug increases survival by approximately two to three months.

Until this last week, Riluzole was the only drug approved for the treatment of ALS.

So what happened this week?

On the 5th May, the FDA announced that they had approved a second drug for the treatment of ALS (Click here for the press release).

It is called Edaravone.

What is Edaravone?

Edaravone is a free radical scavenger – a potent antioxidant – that is marketed as a neurovascular protective agent in Japan by Mitsubishi Tanabe Pharma Corporation.

An antioxidant is simply a molecule that prevents the oxidation of other molecules

Molecules in your body often go through a process called oxidation – losing an electron and becoming unstable. This chemical reaction leads to the production of what we call free radicals, which can then go on to damage cells.

What is a free radical?

A free radical is simply an unstable molecule – unstable because they are missing electrons. They react quickly with other molecules, trying to capture the needed electron to re-gain stability. Free radicals will literally attack the nearest stable molecule, stealing an electron. This leads to the “attacked” molecule becoming a free radical itself, and thus a chain reaction is started. Inside a living cell this can cause terrible damage, ultimately killing the cell.

Antioxidants are thus the good guys in this situation. They are molecules that neutralize free radicals by donating one of their own electrons. The antioxidant don’t become free radicals by donating an electron because by their very nature they are stable with or without that extra electron.

Thus when we say ‘Edaravone is a free radical scavenger’, we mean it’s really good at scavenging all those unstable molecules and stabilising them.

It is an intravenous drug (injected into the body via a vein) and administrated for 14 days followed by 14 days drug holiday.

So, again what has this got to do with Parkinson’s disease?

Well, it is easier to start a clinical trial of a drug if it is already approved for another disease.

And the good news is: Edaravone has been shown to be neuroprotective in several models of Parkinson’s disease.

In this post, we’ll lay out some of the previous research and try to make an argument justifying the clinical testing of Edaravone in Parkinson’s disease

Ok, so what research has been done so far in models of Parkinson’s disease?

The first study to show neuroprotection in a model of Parkinson’s disease was published in 2008:

2008-1

Title: Role of reactive nitrogen and reactive oxygen species against MPTP neurotoxicity in mice.
Authors: Yokoyama H, Takagi S, Watanabe Y, Kato H, Araki T.
Journal: J Neural Transm (Vienna). 2008 Jun;115(6):831-42.
PMID: 18235988

In this first study, the investigators assessed the neuroprotective properties of several drugs in a mouse model of Parkinson’s disease. The drugs included Edaravone (described above), minocycline (antibiotic discussed in a previous post), 7-nitroindazole (neuronal nitric oxide synthase inhibitor), fluvastatin and pitavastatin (both members of the statin drug class).

With regards to Edaravone, the news was not great: the investigators found that Edaravone (up to 30mg/kg) treatment 30 minutes before administering a neurotoxin (MPTP) and then again 90 minutes afterwards had no effect on the survival of the dopamine neurons (compared to a control treatment).

Not a good start for making a case for clinical trials!

This research report, however, was quickly followed by another from an independent group in Japan:

BMC

Title: Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons.
Authors: Yuan WJ, Yasuhara T, Shingo T, Muraoka K, Agari T, Kameda M, Uozumi T, Tajiri N, Morimoto T, Jing M, Baba T, Wang F, Leung H, Matsui T, Miyoshi Y, Date I.
Journal: BMC Neurosci. 2008 Aug 1;9:75.
PMID: 18671880            (This article is OPEN ACCESS if you would like to read it)

These researchers did find a neuroprotective effect using Edaravone (both in cell culture and in a rodent model of Parkinson’s disease), but they used a much higher dose than the previous study (up to 250 mg/kg in this study). This increase in dose resulted in a graded increase in neuroprotection – interestingly, these researchers also found that 30mg/kg of Edaravone had limited neuroprotective effects, while 250mg/kg exhibited robust dopamine cell survival and rescued the behavioural/motor features of the model even when given 24 hours after the neurotoxin.

The investigators concluded that “Edaravone might be a hopeful therapeutic option for PD, although several critical issues remain to be solved, including high therapeutic dosage of Edaravone for the safe clinical application in the future”

This results was followed by several additional studies investigating edaravone in models of Parkinson’s disease (Click here, here and here to read more on this). Of particular interest in all of those follow up studies was a report in which Edaravone treatment resulted in neuroprotective in genetic model of Parkinson’s disease:

2013-1

Title: Edaravone prevents neurotoxicity of mutant L166P DJ-1 in Parkinson’s disease.
Authors: Li B, Yu D, Xu Z.
Journal: J Mol Neurosci. 2013 Oct;51(2):539-49.
PMID: 23657982

DJ-1 is a gene that has been associated Parkinson’s disease since 2003. The gene is sometimes referred to as PARK7 (there are now more than 20 Parkinson’s associated genomic regions, which each have a number and are referred to as the PARK genes). Genetic mutations in the DJ-1 gene can result in an autosomal recessive (meaning two copies of the mutated gene are required), early-onset form of Parkinson disease. For a very good review of DJ-1 in the context of Parkinson’s disease, please click here.

The exact function of DJ-1 is not well understood, though it does appear to play a role in helping cells deal with ‘oxidative stress’ – the over-production of those free radicals we were talking about above. Now given that edaravone is a potent antioxidant (reversing the effects of oxidative stress), the researchers conducting this study decided to test Edaravone in cells with genetic mutations in the DJ-1 gene.

Their results indicated that Edaravone was able to significantly reduce oxidative stress in the cells and improve the functioning of the mitochondria – the power stations in each cell, where cells derive their energy. Furthermore, Edaravone was found to reduce the amount of cell death in the DJ-1 mutant cells.

More recently, researchers have begun digging deeper into the mechanisms involved in the neuroprotective effects of Edaravone:

2015-1

Title: Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress.
Authors: Jami MS, Salehi-Najafabadi Z, Ahmadinejad F, Hoedt E, Chaleshtori MH, Ghatrehsamani M, Neubert TA, Larsen JP, Møller SG.
Journal: Neurochem Int. 2015 Nov;90:134-41.
PMID: 26232623             (This article is OPEN ACCESS if you would like to read it)

The investigators who conducted this report began by performing a comparative two-dimensional gel electrophoresis analyses of cells exposed to oxidative stress with and without treatment of Edaravone.

Um, what is “comparative two-dimensional gel electrophoresis analyses”?

Good question.

Two-dimensional gel electrophoresis analyses allows researchers to determine particular proteins within a given solution. Mixtures of proteins are injected into a slab of gel and they are then separated according to two properties (mass and acidity) across two dimensions (left-right side of the gel and top-bottom of the gel).

A two-dimensional gel electrophoresis result may look something like this:

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Two-dimensional gel electrophoresis. Source: Nature

As you can see, individual proteins have been pointed out on the image of this slab of gel.

In comparative two-dimensional gel electrophoresis, two samples of solution are analysed by comparing two slabs of gel that have been injected with protein mix solution from two groups of cells treated exactly the same except for one variable. Each solution gets its own slab of gel, and the differences between the gel product will highlight which proteins are present in one condition versus the other (based on the variable being tested).

In this experiment, the variable was Edaravone.

And when the researchers compared the proteins of Edaravone treated cells with those of cells not treated with Edaravone, they found that the neuroprotective effect of Edaravone was being caused by an increase in a protein called Peroxiredoxin-2.

Now this was a really interesting finding.

You see, Peroxiredoxin proteins are a family (there are 6 members) of antioxidant enzymes. And of particular interest with regards to Parkinson’s disease is the close relationship between DJ-1 (the Parkinson’s associated protein discussed above) and peroxiredoxin proteins (Click here, here, here and here to read more about this).

In addition, there are also 169 research reports dealing with the peroxiredoxin proteins and Parkinson’s disease (Click here to see a list of those reports).

So, what do you think about a clinical trial for Edaravone in Parkinson’s disease?

Are you convinced?

Regardless, it an interesting drug huh?

Are there any downsides to the drug?

One slight issue with the drug is that it is injected via a vein. Alternative systems of delivery, however, are being explored.A biotech company in the Netherlands, called Treeway is developing an oral formulation of edaravone (called TW001) and is currently in clinical development.

Edaravone was first approved for clinical use in Japan on May 23, 2001. With almost 17 years of Edaravone clinical use, a few adverse events including acute renal failure have been noted, thus precautions should be taken with individuals who have a history of renal problems. The most common side effects associated with the drug, however, are: fatigue, nausea, and some mild anxiety.

Click here for a good overview of the clinical history of Edaravone.

So what does it all mean?

The announcement from the FDA this week regarding the approval of Edaravone as a new treatment for ALS represents a small victory for the ALS community, but it may also have a significant impact on other neurodegenerative conditions, such as Parkinson’s disease.

Edaravone is a potent antioxidant agent, which has been shown to have neuroprotective effects in various models of Parkinson’s disease and other neurodegenerative conditions. It could be interesting to now test the drug clinically for Parkinson’s disease. Many of the preclinical research reports indicate that the earlier Edaravone treatment starts, the better the outcomes, so any initial clinical trials should focus on recently diagnosed subjects (perhaps even those with DJ-1 mutations).

The take home message of this post is: given that Edaravone has now been approved for clinical use by the FDA, it may be advantageous for the Parkinson’s community to have a good look at whether this drug could be repurposed for Parkinson’s disease.

It’s just a thought.


The banner for today’s post was sourced from Forbes

Busy day for Parkinson’s – 9/2/2017

 

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Today there was a lot of Parkinson’s related activity in the news… well, more than usual at least.

Overnight there was the publication of a blood test for Parkinson’s disease, which looks very sensitive. And this afternoon, Acorda Therapeutics announced positive data for their phase three trial.

In this post, we’ll look at what it all means.


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Blood cells. Source: Reference.com

Today we found out about an interesting new study from scientists at Lund University (Sweden), where they are developing a test that can differentiate between different types of Parkinsonisms (See our last post about this) using a simple blood test.

We have previously reported about an Australian research group working on a blood test for Parkinson’s disease, but they had not determined whether their test could differentiate between different kinds of neurodegenerative conditions (such as Alzheimer’s disease). And this is where the Swedish study has gone one step further…

blood
Title: Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder
Authors: Hansson O, Janelidze S, Hall S, Magdalinou N,  Lees AJ, Andreasson U, Norgren N, Linder J, Forsgren L, Constantinescu R, Zetterberg H, Blennow K, & For the Swedish BioFINDER study
Journal: Neurology, Published online before print February 8, 2017
PMID: N/A       (This article is OPEN ACCESS if you would like to read it)

The research group in Lund had previously demonstrated that they could differentiate between people with Parkinson’s disease and other types of Parkinsonism to an accuracy of 93% (Click here to read more on this). That is a pretty impressive success rate – equal to basic clinical diagnostic success rates (click here for more on this).

The difference was demonstrated in the levels of a particular protein, neurofilament light chain (or Nfl). NfL is a scaffolding protein, important to the cytoskeleton of neurons. Thus when cells die and break up, Nfl could be released. This would explain the rise in Nfl following injury to the brain. Other groups (in Germany and Switzerland) have  also recently published data suggesting that Nfl could be a good biomarker of disease progression (Click here to read more on this).

There was just one problem: that success rate we were talking about above, it required cerebrospinal fluid. That’s the liquid surrounding your brain and spinal cord, which can only be accessed via a lumbar puncture – a painful and difficult to perform procedure.

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Lumbar puncture. Source: Lymphomas Assoc.

Not a popular idea.

This led the Swedish researchers to test a more user friendly approach: blood.

In the current study, the researchers took blood samples from three sets of subjects:

  • A Lund set (278 people, including 171 people with Parkinson’s disease (PD), 30 people with Multiple system atrophy (MSA), 19 people with Progressive Supranuclear Palsy (PSP), 5 people with corticobasal syndrome (CBS), and 53 people who were neurologically healthy (controls).
  • A London set (117 people, including 20 people with PD, 30 people with MSA, 29 people with PSP, 12 people with CBS, and 26 neurologically healthy controls
  • An early disease set (109 people, including 53 people with PD, 28 people with MSA, 22 people with PSP, 6 people with CBS). All of the early disease set had a disease duration less than 3 years.

When the researchers looked at the levels of NfL in blood, they found that they could distinguish between people with PD and people with PSP, MSA, and CBS with an accuracy of 80-90% – again a very impressive number!

One curious aspect of this finding, however, is that the levels of Nfl in people with PD are very similar to controls. So while this protein could be used to differentiate between PD and other Parkinsonisms, it may not be a great diagnostic aid for determining PD verses non-PD/healthy control.

In addition, what could the difference in levels of Nfl between PD and other Parkinsonisms tell us about the diseases themselves? Does PD have less cell death, or a more controlled and orderly cell death (such as apoptosis) than the other Parkinsonisms? These are questions that can be examined in follow up work.


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Source: 3rd-Solutions

Like we said at the top, it’s been a busy day for Parkinson’s disease: Good news today for Acorda Therapeutics, Inc.

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Source: Acorda

They announced positive Phase 3 clinical trial results for their inhalable L-dopa treatment, called CVT-301, which demonstrated a statistically significant improvement in motor function in people with Parkinson’s disease experiencing OFF periods.

We have previously discussed the technology and the idea behind this approach to treating Parkinson’s disease (Click here for that post).

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The ARCUS inhalation technology. Source: ParkinsonsLife

Basically, the inhaler contains capsules of L-dopa, which are designed to break open so that the powder can escape. By sucking on the inhaler (see image below), the open capsule starts spinning, releasing the levodopa into the air and subsequently into the lungs. The lungs allow for quicker access to the blood system and thus, the L-dopa can get to the brain faster. This approach will be particularly useful for people with Parkinson’s disease who have trouble swallowing pills/tablets – a common issue.

The Phase 3, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of CVT-301 when compared with a placebo in people with Parkinson’s disease who experience motor fluctuations (OFF periods). There were a total of 339 study participants, who were randomised and received either CVT-301 or placebo. Participants self-administered the treatment (up to five times daily) for 12 weeks.

The results were determined by assessment of motor score, as measured by the unified Parkinson’s disease rating scale III (UPDRS III) which measures Parkinson’s motor impairment. The primary endpoint of the study was the amount of change in UPDRS motor score at Week 12 at 30 minutes post-treatment. The change in score for CVT-301 was -9.83 compared to -5.91 for placebo (p=0.009). A negative score indicates an improvement in overall motor ability, suggesting that CVT-301 significantly improved motor score.

The company will next release 12-month data from these studies in the next few months, and then plans to file a New Drug Application (NDA) with the Food and Drug Administration (FDA) in the United States by the middle of the year and file a Marketing Authorization Application (MAA) in Europe by the end of 2017. This timeline will depend on some long-term safety studies – the amount of L-dopa used in these inhalers is very high and the company needs to be sure that this is not having any adverse effects.

All going well we will see the L-dopa inhaler reaching the clinic soon.


 

The banner for today’s post was sourced from the Huffington Post

A brave new world: 21st Century Cures Act

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In one of his last acts as President, this week Barrack Obama signed into law the 21st Century Cures Act. Enacted by the 114th United States Congress, the new law will have enormous implications for the American health system and for the Parkinson’s community.

In today’s post we’ll review the new law and what it will mean for Parkinson’s disease.


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An early version of the hypocratic oath. Source: Wikipedia

It may surprise you, but contrary to popular belief the phrase “First do no harm” (Latin: Primum non nocere) does not appear in the Hippocratic oath that medical practitioners are suppose to abide to.

Not now, nor in the original form.

The closest we get to it is (Greek) noxamvero et maleficium propulsabo (“I will utterly reject harm and mischief”). Despite this, the basic idea of ‘not doing harm’ has been part of the foundation of medical practise since the oath was first written around the 3rd century BCE.

The idea of ‘doing no harm’, however, presents a double-edge sword for practitioners when they are faced with patients prepared to try anything to cure themselves of a crippling condition. Does the practitioner knowingly consent to allowing a subject to take a treatment that could have negative side-effects or no effect at all?

The example above is provided simply to set the stage for the discussion below. For we are about to embark on a new age when practitioners will potentially be faced with this dilemma on an ever more frequent basis.

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The United States Capitol. Source: SpotHeroBlog

The ‘Science of Parkinson’s’ is politically neutral.

We do, however, investigate proposals and new legislations that will affect the Parkinson’s community, particularly those affecting the research world.

With that said, on the 13th December 2017, President Barrack Obama signed into law one of the most sweeping efforts to provide additional support and funding for health conditions that we have seen for some time. The 21st Century Cures Act (catchy name huh?) is going to have a big impact.

What is in the new law?

The law focuses on cancer, Alzheimer’s disease, opioid addiction, medical devices, access to new drugs, and mental health.

The new law provides $4.8 billion for three of the Obama administration’s key research programs over the next 10 years: Vice President Joe Biden’s cancer moonshot, the BRAIN Initiative, and the Precision Medicine Initiative. It will also give states $1 billion to fight the opioid crisis currently affecting certain areas of the country, and deliver an additional $500 million to the Food and Drug Administration (FDA).

In addition, the ‘Cures’ law will create new databases that will access health records and allow for a greater collection of information focused on certain diseases. Of particular interest to us is the creation of the ‘National Neurological Conditions Surveillance System’ at the Centers for Disease Control and Prevention (CDC), which will collect demographic information on people living with neurological diseases, like Parkinson’s disease.

Critically, the ‘Cures’ law will speed up the regulatory process for getting new treatments and devices approved for the clinic. Currently it can take up to a decade and a billion dollars to get new drugs from the lab bench to the clinic. Patient groups have been lobbying hard for this and they will be very happy with the Act being passed into law.

Who benefits from this new law?

With every new law there are winners and losers:

Winners:

1. Pharmaceutical and Medical Device Companies. The law will give the FDA new authority to request fewer studies from those companies trying to bring new products to the clinic. In theory this should speed up the approval process. Critics worry that this will result in a lowering of standards and bring products to the clinic that haven’t been properly tested (According to disclosures, 58 pharmaceutical companies, 24 device companies and 26 “biotech products and research” companies have spent more than $192 million on lobbying for this new law).

2. Patient groups. As we mentioned above, patient advocacy groups have lobbied very hard for this new law (spending $4.6 million according to disclosures). The law also includes the allowance for more patient input in the drug development and approval process. This aspect alone will be a boost to the clout of such groups.

3.  Health information technology companies. The law urges federal agencies and health providers nationwide to use electronic health records systems and to collect data to enhance research and treatment (the only caveat here is that this section is unfunded by the new law). Computer companies were apparently very keen on this aspect of the new law, however, as they too have been lobbying hard.

We wanted to write that Medical schools and research hospitals may benefit since the law provides $4.8 billion over 10 years in additional funding to the federal government’s main biomedical research organisation, National Institutes of Health (NIH). It should be noted, however, that these funds are not guaranteed and will be subject to annual appropriations. So we’ll hold off stating that research is a winner until this is resolved.

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President Obama hard at work. Source: Fastcompany

Losers:

1.  Preventive medicine groups. $3.5 billion — about 30 percent — of the Prevention and Public Health Fund will be cut. This fund was established under ‘Obamacare’ to promote prevention of Alzheimer’s disease, hospital acquired infections, chronic illnesses and other ailments. Obviously certainly things have to be cut in order to fund other aspects of this new law, but this particular cut is going to hurt some affected groups.

2.  The FDA. While the FDA will be given an additional $500 million (through to 2026), this amount is not enough to cover the additional workload resulting from the law. In addition, the agency has been pushing hard for extra funding to deal with deteriorating facilities, but there was nothing to cover this in the new law.

In addition, the FDA has to deal with the renewal of a controversial voucher system which rewards companies that receive approval for new treatments dealing with ‘rare pediatric diseases‘. Upon approval the company will receive a voucher that can be redeemed later and allows the company to receive a priority review of a marketing application for a different product.

3.  Randomised clinical trials. The gold standard for testing the safety and efficacy of new drugs and devices is the randomised clinical trial. The new law, however, directs the FDA to evaluate the use of “real world evidence” for approval of new indications for FDA-approved drugs. This may result in randomised clinical trials will become less important for drug and device approval.

Currently getting a drug or a medical device approved by the FDA and into the clinic, companies have to go through a rigorous screening process, included randomized double-blind clinical trials. With the 21st Century Cures Act, that process will be sped up by allowing the use of anecdotal evidence and observational data to clear a drug for approval. That is to say, patient feedback might be used to help get drugs into the clinic more quickly.

loyalty-drivers-in-the-consumer-healthcare-market

Source: DunnHumby

Getting treatments to the clinic sooner is a good though, right?

Critics of the new law, such as Public Citizen’s Health Research Group, are worried that the new law is relaxing the standards too much. For example they believe the designation of  “breakthrough” devices is too broad, and could lead to clearance of devices that aren’t ready for the market.

Neutral as we are here at the SoPD, we have to agree that there is the potential for real problems here. While we are as desperate as everyone else in the Parkinson’s community for new treatment, we have to be sure that those novel therapies are safe. Any lowering of standards will increase the likelihood of ineffective treatments coming to market.

What does it all mean for Parkinson’s disease?

There are a lot of positives for the Parkinson’s community resulting from this new law:

1.  The development of infrastructure to collect data on neurological diseases to better understand Parkinson’s is a good thing.

As the Micheal J Fox Foundation (MJFF) points out, we currently do not have really accurate information about how many people are living with Parkinson’s disease, let alone where they are located or who they are based on gender, ethnicity, etc. Critical pieces of information might be missing from our understanding of the disease based on the absence of such information.

2.  Extra funding for the Obama administration research initiatives to further our knowledge of the brain and developing individualized treatments is a good thing.

The ‘Cures law’ has allocated $1.5 billion over the next ten years to the NIH for the BRAIN Initiative. This will have benefits for Parkinson’s research. In addition, $30 million has been allocated for clinical research to further the field of regenerative medicine using stem cells.

3.  Speeding up the regulatory process and accounting for ‘real world observations’

The new law will make it easier for companies to bring new treatments to the clinic. Reducing the number of tests, and thus reducing the regulatory cost, may result in pharmaceutical companies being prepared to take more treatments to the FDA for approval.

In addition, the FDA will now be required to take patient perspectives into account in the drug approval process and the new law tasks the agency with creating a framework for collecting patient experience data.

This data will be collected from various sources (patients, family members and caregivers, patient advocacy organizations, disease research foundations, researchers and drug manufacturers), and it will detail a patient’s experience with a disease or therapy, taking into account the impact it has on their lives.

By involving patients/carers/families in this manner, it is hoped that government regulators will be more in touch with the community’s experiences and priorities as new drugs and devices enter late-stage clinical testing and move toward FDA approval.

What does it all mean?

It will be interesting to see how this new law impacts medical regulators globally. The US FDA is already considered to be a ‘fast mover’ when compared with other regulatory bodies. Whether these international counterpart will follow suit will be interesting to watch.

Bring treatments to market quicker, having more information regarding disease, and having a more patient-centric approach are all good aspects to this new law. As we have suggested above, however, there will be new potential for the system to be abused. Profit motivated companies will naturally look to game this new law to get their products to market.

And this may well result in medical practitioners being confronted by that double-edged sword dilemma we discussed at the start of this post. For now, all we can really so is sit back and see what happens.

If we thought 2016 was full of surprises, we can only imagine what 2017 will bring!


The banner for today’s post was sourced from Fanshare