Clinical trial Archives - Retina Specialist | Fairfax, Virginia

Implantable Telescope is Available!

CentraSight, the implantable telescope for macular degeneration, is now available! CMS (Centers for Medicare and Medicaid Services) has approved the telescope for those patients with macular degeneration meeting the eligibility criteria for the surgical procedure.

Medicare/Medicaid will cover the cost of the implant and the surgery in certain patients as October 1, 2011! For now, the procedure has a designation of a transitional pass-through payment, that is, CMS will approve the procedure for 2-3 years until enough payment data can be collected.

The Telescope Improves Vision

To achieve this milestone, Visioncare, the parent company, needed to show that the implantable telescope for macular degeneration met several criteria;

FDA Approval
CMS deems reasonable and necessary
Device offers Substantial Clinical Improvement

FDA Approval: VisionCare received FDA approval for their telescope last August.

Substantial Clinical Improvement may be difficult to attain as the device must surpass some steep challenges. In order to achieve this status, one of the following situations must be true;

the new device must be better than other available treatments
the device improves the ability to diagnose a condition
the device significantly improves the patient (i.e. clinical outcomes)

Availability of the CentraSight Telescope

For now, according to my contact at VisionCare, CentraSight will be offered at the locations where the original clinical trials were performed. This has been their plan all along. With time, as more physicians become trained, the availability will widen.

What Does This Mean? This is the first real step to helping patients with significant visual loss in both eyes. The surgery to insert the “telesope” is similar to cataract implantation, yet the CentraSight will modify the images so more of the retina surrounding the macula is utilized for vision.

While patients with either form of the disease might be candidates, this is the first FDA sanctioned “therapy” for patients with severe loss of vision from dry ARMD.

This is not a cure or a “fix” for loss of central vision, however, the telescope does improve function for those that have no central vision from the disease and can lead to am improvement in the quality of life.

VEGF-Trap Gets Closer to FDA Approval

VEGF Trap for Macular Degeneration and Diabetic Macular Edema

VEGF-Trap (aka aflibercept), another anti-VEGF drug, moves closer to FDA approval as it received “priority review” status. This status means that the FDA process will be accelerated and the drug can be reviewed in 6 months versus the usual 10 month period. Alfibercept is another injectable drug that may have an effect on choroidal neovascularization in wet macular degeneration.

In the press release, Regeneron Pharmaceuticals, Inc., cited an incidence of almost 200,000 new cases of wet ARMD in the U.S. alone. It is the leading cause of new blindness in patients 65 and older.

As with it’s predecessors, Macugen and Lucentis, the company must prove to the FDA that the drug is effective and safe.

Regeneron has also started Phase III clinical trials for VEGF-Trap for the treatment of diabetic macular edema. There will be two studies, an international study and a North American study. These trials, too, will be conducted to test the safety and efficacy of alibercept for retinal swelling caused by diabetic retinopathy, or diabetic macular edema.

Diabetic macular edema is the leading cause of decreased vision in patients with diabetes under the age of 50. Similar studies are underway for Lucentis and Avastin.

What Does This Mean?

On one hand, this is not new news. Macugen, Lucentis and Avastin have been used for several years for the treatment of wet macular degeneration. VEGF-trap is the same type of drug as the aforementioned. VEGF-trap is likely, in my opinion, to gain FDA approval if; it improves vision better than Lucentis and/or it requires fewer repeat injections to stableize the eye.

On the other hand, using VEGF-Trap for the treatment of diabetic retinopathy will be the first drug to gain FDA approval. Until now, we (retinal specialists) have been using Avastin and Lucentis “off label” for the treatment of DME. Approval of VEGF-Trap will validate our suspicions that this is a worthwhile treatment for diabetic retinopathy.

FDA Denies Iluvien

Iluvien Denied by FDA

The Food and Drug administration fails to approve Iluvien for the treatment of diabetic retinopathy and cites the need for more safety information in addition to concerns about the safety of the manufacturing process of Iluvien. Alimera Sciences had hoped to gain approval by the end of December 2010, instead, it was told by the FDA that more information was needed.

Safety and Efficacy of Iluvien

Data from almost 1000 patients were included in the FDA submission. If you remember, Alimera Sciences received a “Priority Review” from the FDA when the application was filed last summer. A “Priority Review” accelerates this last leg of the FDA approval process.

Instead, the FDA is asking for additional safety/efficacy information covering 36 months after treatment instead of the 24 months provided.

Is Manufacturing Safe?

There were also concerns regarding the manufacturing, packaging and sterilization of Iluvien, though no specifics were noted.

What Does this Mean?

We’ve now heard about Iluvien for diabetic macular edema for over a year. At the outset, the news has been promising and the technology exciting. For patients with diabetic macular edema, this drug promises options to the old standby …laser treatment.

Iluvien may be the second drug approved that is based on technology to offer sustained drug delivery into the eye. Ozurdex, a similar product, has been in use since the summer of 2009 and is used for retinal vein occlusions.

While promising, the FDA plods slowly, yet thoroughly. The request for additional data indicates that this product is probably effective for treating macular edema, yet recommendations need to be made regarding is use. Hence, the need for additional dtate.

Had the product been rejected, or requests for additional clinical trials, this would have been a clearer signal of failure.

In the end, though disappointing, the company hopes to have a marketable product by the end of 2011.

Hang in there.

Update on Implantable CentraSight Telescope

VisionCare’s implantable telescope for patients with advanced macular degeneration was FDA approved in August. Since then, little information has been available, but I received an update from the company last week.

Telescope is Not Being Shipped

Though FDA approval has been received, VisionCare, the parent company, has not started shipping this implantable device. The company is quite small and is gearing up for market release. Reading between the lines, this may occur in the next 6 months.

Medicare Reimbursement

In simplest terms, Medicare has yet to approve this device for insurance coverage, that is, they haven’t agreed to pay for it yet. The parent company must submit an application based upon the FDA approval and the fact that this is a brand new type of medical device.

Obviously, VisionCare isn’t going to ship the Centrasight telescope if it isn’t going to be covered by insurance.

Training Centers for Eye Doctors

If you read my last article regarding the CentraSight, the implantation of the telescope involves a team approach and, thus, training for all the eye professionals involved. Training will be required for the surgeons, eye doctors, nurses, technicians, etc.

The company is hopeful to start the initial “launch” at the centers involved in the clinical trials. Additional sites and doctors will be added as time goes on. My own practice is hopeful to be one of the first to train.

Information for Patients

Additional information has been provided on the CentraSite web page.

What Does This Mean? At the very least, the telescope will have limited availability for the first half of the year. Without Medicare approval, the device simply won’t be marketed. The development of other centers for the device to be implanted will depend upon the initial revenues and popularity of the device. This is not unlike cell phone coverage.

The CentraSight telescope is also a good example of how the FDA and Medicare together to bring devices to market. FDA approval doesn’t mean Medicare’s endorsement as the two operate independently.

Overall, there are many variables to watch; the speed or rate in which new centers are developed and new doctors trained and the fiscal issue of insurance payment. Be patient.

Iluvien Treatment for Diabetic Macular Edema

Iluvien gets closer to FDA approval for treatment of diabetic macular edema. Earlier this week, I wrote about emerging treatments for diabetic retinopathy. Of the group, Iluvien is now the most likely to be available.

Alimera Sciences has filed for NDA (New Drug Application) for Iluvien. In March, the company announced the favorable results in their clinical trials for the FDA. The NDA is the last step for FDA approval.

Iluvien Releases Steroid

Iluvien is a sustained release drug delivery system. Similar to Ozurdex, the delivery system will release steroid after injection into the eye. (Ozurdex is presently FDA approved for retinal vein occlusions, not diabetic retinopathy. The makers of Ozurdex are hopeful that it may be used for diabetes.)

The steroid released by Iluvien, fluocinolone, will last for 24 months after injection. The vehicle will remain in the eye after the drug is released.

Alternative to Present Treatments

The present treatment for diabetic macular edema involves laser treatment, anti-VEGF injections and/or steroid injections. The laser treatment has limited applications, that is, it can’t be used in all patients and also doesn’t work as well as any of the injections.

The injections, on the other hand, don’t last long and need to be repeated.

Iluvien may obviate the need for repeated treatments and offer significant improvement in vision compared to the standard laser therapy. With fewer injections, there is less chance of infection.

What Does This Mean? Ozurdex was FDA approved about one year ago. The significance of Iluvien’s NDA is the validation of the advantages of intraocular sustained release drug systems.

All emerging treatments for diabetic macular edema involve injections. All seem to offer superior treatment compared to the standard of care, laser photocoagulation. A sustained release system for diabetic retinopathy will change the way we treat this very common eye disease.

The introduction of Iluvien is estimated to be towards the end of the year according to this week’s press release.

I can’t wait.

How Many Lucentis Injections?

How many anti-VEGF injections of Avastin or Lucentis are needed to treat wet macular degeneration? We don’t know. While there is no question that anti-VEGF injections are the gold-standard for the treatment of ARMD, the exact way in which they are used varies from doctor to doctor.

Standard of Care

The standard of care for macular degeneration changed. The standard treatment for wet ARMD was Visudyne and before Visudyne, laser treatment.

Since Macugen, the initial anti-VEGF medication, other accepted standards have evolved including Lucentis and Avastin.

In the medical world, these are still “new” treatments and we are still finding our way. We are always looking to improve our treatments.

FDA Approval

In short, FDA Approval is needed to get a new drug introduced to the market. To state another way, FDA approval is needed to make it legal for a company, in the United States, to sell a drug.

Once available on the market, however, the way in which the drug is utilized varies from doctor to doctor.

Testing Serves as a Guideline

When a drug is initially sent to the FDA for approval, careful testing (clinical trials) must be completed proving safety and efficacy of the drug. The drug company must prove that it is safe in humans and that the drug does what the company claims it does.

For example, in the case of Macugen or Lucentis the treatment protocol used in the study (to prove the drug works) may have required injections every 6 weeks for more than a year. During these studies, there is strict adherence to the protocol. Little variation is allowed. For instance, every six weeks means every six weeks. If a patient were to receive an injection other than the 6 week interval, that patient may be removed from the study.

It’s Called Practice

When first introduced, everyone (doctors) followed a very similar protocol. We followed the protocol that was recommended by the manufacturer. They can only recommend the protocol approved by the FDA. That protocol is usually the same one that was included in the original study series.

With time, doctors get familiar with the drug and gain experience using the drug. Real life situations are not as stringent as FDA studies. We may find that if Mr. “Macugen” missed an injection, he does okay anyway. We may find that Ms. Lucentis can’t get an injection in 6 weeks, but can come in at 5 weeks.

Other studies, not necessarily for FDA purposes, emerge from our academic colleagues that change protocols, too. Perhaps a study is published from Johns Hopkins purporting great results using injections every week. Guess what, it’ll change how we practice.

Studies of related products also change how we practice. For instance, the protocols used for studies involving any of the anti-VEGF medications impact the use of the other drugs.

What Does This Mean? Treatments vary from doctor to doctor. The better a treatment, the more variation…in my opinion. The best treatments are inherently really good and do not require strict methods of employment.

Like a good recipe, a good treatment is hard to mess up.

Iluvien: New Drug for Diabetic Macular Edema

Iluvien™, a new drug for the treatment of diabetic macular edema, draws one step closer to FDA approval. Alimera Sciences/pSivida announced that Iluvien showed favorable results in two Phase 3 clinical trials. The company has announced they will file for a New Drug Application (NDA) based on the favorable results.

Iluvien is a Sustained Release Drug Delivery System

Iluvien releases fluocinolone acetonide, a well studied steroid, after injection into the eye. Intraocular injections have become a popular method for treating a variety of retinal disorders including macular degeneration and diabetic macular edema. The injections are performed in an office setting.

The drug will be released for 24-36 months. The delivery system is based upon the Medidur™ delivery platform. Medidur is the proprietary delivery system that, when coupled with fluocinolone acetonide, is dubbed Iluvien. The platform does not dissolve and remains inside the eye.

Results of the Clinical Trials

Basically, the steroid implant improved vision in almost twice as many patients as those treated with placebo. In addition, 75% of patients required only one application of the device.

New Drug Application is Last Step for FDA Approval

The last step for Iluvien is now to gain the coveted FDA approval. The last step following Phase 3 clinical trials is for Alimera Sciences (licensee of Iluvien from manufacturer pSivida) to file a New Drug Application. It expects to file by the end of the 2nd quarter of this year.

Remember Ozurdex?

Ozurdex™ received FDA approval last summer for the treatment of retinal vein occlusions; branch retinal vein occlusion and central retinal vein occlusion. Like Iluvien, Ozurdex releases steroid over a period of months. The major difference between the two technologies is the specific type of steroid (Ozurdex releases dexamethasone), duration of release and the FDA guidelines for use.

Iluvien is most likely going to be the first drug FDA approved for the treatment of diabetic macular edema, whereas, Ozurdex is the first for treatment of retinal vein occlusions.

What Does This Mean? One year ago, sustained release drug delivery did not technically exist in ophthalmology. By this summer, there may be a second delivery system for treatment of retinal disease. Clearly the tide is turning in terms of the way we can treat eye disease.

It is quite likely that other drugs will follow…we are anxiously awaiting the first sustained release system for macular degeneration.

I believe that sustained release technology will evolve to treat other eye diseases as well, not just retinal disease. For instance, what if there were no longer eye drops needed for glaucoma?

Standard of Care vs. FDA Approved – How We Choose a Treatment

Avastin® is not FDA (Food and Drug Administration) approved for treating wet macular degeneration, but it is the standard of care for treating the disease. The FDA has given approval for Avastin to be used to treat a variety of cancers, but nothing about eyes.

What is Standard of Care? Standard of care is the treatment that another prudent healthcare professional, of similar backgrounds and training, would give to the same patient. As an example, if I choose to treat you with Lucentis for wet macular degeneration and I am complying with the local standard of care, another retina specialist practicing across the street, would choose the same treatment for you.

What About FDA Approval? Last post, we spoke about evidenced based medicine and the need for a new drug to gain FDA approval. Once a drug gains FDA approval, it may be used “off-label.” Off-label indicates that healthcare providers have found other uses for the drug, in addition to the FDA indication.

Avastin is used “off-label” for the treatment of wet macular degeneration. Avastin has FDA approval for the treatment of certain colon, breast, lung, kidney and brain tumors.

What About Lucentis? Lucentis® is made by the same manufacturer as Avastin (Genentech/Roche). That manufacturer did go through clinical trials, and costs, of getting FDA approved for wet macular degeneration.

Avastin and Lucentis are chemically very similar, they are cousins. One is much more expensive than the other. Both are anti-VEGF treatments.

On Becoming the Standard of Care In this case, several people receiving chemotherapy for colon cancer started reporting that their vision was improving. Some smart docs paid attention to these comments. In short, because of the similarities, Avastin was soon used for intraocular injection.

The doctors that pioneered this approach designed a few “randomized” studies and reported their results at our industry meetings. Others repeated similar studies and were finding the same results.

This then becomes intriguing for community physicians (like yours truly) and we try it ourselves. If it works, we embrace the new “off-label” treatment.

What Does This Mean? In the case of Lucentis and Avastin, this means that we use a similar drug, get similar (or perhaps even better) results, but significant cost savings. From a healthcare point of view, while Avastin was never FDA approved, the industry provides its own proof.

This is still evidenced based medicine. While the traditional FDA clinical trials were not performed, similar trials are usually performed by institutions or groups of doctors that feel a new use, or indication, for a treatment is possible. The trials are usually shorter and focused on efficacy of the new treatment. The best “studies” are those that are prospective, randomized and double blinded. These ensure the accuracy of any results. The results are presented at meetings and in so-called “peer reviewed” journals. It is in this arena, that we decide, outside of government (i.e. FDA) sanction, if new treatments are worthwhile.

It is at this level, we read a plethora of “studies” making claims. There are good and bad studies. This is where we need to “read critically.”

“Randy”

Randall V. Wong, M.D.
Ophthalmologist, Retina Specialist
Fairfax, Virginia

Iluvien® For Diabetic Macular Edema Has Eyes on FDA

™Alimera Sciences’ “Iluvien®” moves closer to FDA approval for the treatment of diabetic macular edema. Iluvien is an extended release drug delivery system designed for direct intravitreal injection to the eye. Iluvien will release a steroid, fluocinolone acetonide, for up to 36 months to treat retinal swelling. The company has announced pivotal results in the ongoing FAME (Fluocinolone acetonide in diabetic macular edema) study. This is a phase 3 FDA clinical trial.

An earlier post covered Iluvien’s safety and efficacy in phase 2 trials for the treatment of diabetic macular edema.

Diabetic Macular Edema is the most common complication of diabetic retinopathy. The traditional laser for diabetic retinopathy has been usual treatment for about 30 years. I have written previously about the emergence of new treatments and new technologies to treat the diabetic macular edema. Intravitreal steroid injections, anti-VEGF and sustained release intraocular drug delivery systems are all the rage.

FDA Clinical Trials dictate how medicines are approved for treatment of disease in the U.S. I have always cautioned that you must consider a “treatment” only if it has already been FDA approved. Most of what is advertised as treatment is neither FDA approved nor even studied.

There are 4 different steps to passing the FDA requirements. There are 3 phases of clinical trials (sometimes an additional phase 4 is required) and the NDA (New Drug Application).

The phase 3 clinical trial (FAME) is almost complete. The study will proceed to 36 months. The early phase 3 findings indicate improvement in vision in about 25-30% of patients after the first 24 months of the study.

What Does This Mean? This is huge. It means that there is merit to what the company anticipates. Technically, phase III trials determine if the drug is useful and confirms safety.

New Drug Application (NDA) is usually the last step for a company, or sponsor, to be allowed to market and sell the drug. Alimera expects NDA submission later in 2010 after completion and analysis of the phase 3 data.

Alimera’s Iluvien is close to reality for the treatment of diabetic macular edema.

For fun, compare the status of this drug, Iluvien, to E10030. I wrote about Ophthotech’s E10030 a few days ago. E10030 is an anti-PDGF aptamer that treats wet macular degeneration. This drug is about to enter phase 2.

“Randy”

Randall V. Wong, M.D.
Ophthalmologist, Retina Specialist
Fairfax Virginia

Tree Bark May Be Beneficial To Diabetics: Supplement or Drug?

“Ever Eat A Pine Tree? Many Parts are Edible.”

That famous line by Euell Gibbons lives on. Now, “researchers” have described that Pycnogenol®, an extract from the bark of the French maritime pine tree, has the potential to improve vision in patients with diabetic retinopathy. The tree is found along the coast of southwest France.

In a small study involving 46 patients with early diabetic retinopathy, 24 patients were given Pycnogenol tablets daily and the remainder were given placebo (sugar pill).

After 2 months, patients taking Pycnogenol had statistically significant improvement in vision and decreased macular edema. An increase in retinal blood flow was also noted. (The standard treatment for diabetic macular edema is laser photocoagulation.)

The researchers think that Pycnogenol (Horphag Research) works by increasing blood flow to the retina that secondarily decreases the diabetic macular edema. Pycnogenol is said to be an antioxidant, anti-inflammatory and aids in vascular dilation.

CAUTION: What Does This Really Mean?

Pycnogenol is not a drug. It is a supplement. There are big differences in the requirements needed to bring a supplement to market vs. a drug.

Pycnogenol is marketed in the United States as a dietary supplement. As such, the manufacturers of dietary supplements do not have to provide safety and health information regarding their products as long as they do not claim the supplements can prevent, treat, or cure any specific disease.

On the other hand, drug manufacturers must submit health and safety data from carefully designed clinical trials to the FDA before marketing their products.

Lastly, supplements are not necessarily tested to find out if they interact with medicines, foods, or other herbs and supplements. Even so, such data is not necessarily available or provided.

Be careful out there! There’s a lot of masquerading of supplements. Be cautious.

“Randy”

Randall V. Wong, M.D.
Ophthalmologist, Retina Specialist
Fairfax, Virginia

Tag Archives: Clinical trial

Implantable Telescope is Available!

The Telescope Improves Vision

Availability of the CentraSight Telescope

VEGF-Trap Gets Closer to FDA Approval

FDA Denies Iluvien

Safety and Efficacy of Iluvien

Is Manufacturing Safe?

Update on Implantable CentraSight Telescope

Telescope is Not Being Shipped

Medicare Reimbursement

Training Centers for Eye Doctors

Information for Patients

Iluvien Treatment for Diabetic Macular Edema

Iluvien Releases Steroid

Alternative to Present Treatments

How Many Lucentis Injections?

Standard of Care

FDA Approval

Testing Serves as a Guideline

It’s Called Practice

Iluvien: New Drug for Diabetic Macular Edema

Iluvien is a Sustained Release Drug Delivery System

Results of the Clinical Trials

New Drug Application is Last Step for FDA Approval

Remember Ozurdex?

Standard of Care vs. FDA Approved – How We Choose a Treatment

Iluvien® For Diabetic Macular Edema Has Eyes on FDA

Tree Bark May Be Beneficial To Diabetics: Supplement or Drug?

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