Is a Cheaper, Off-Label Drug Better for Diabetic Eye Disease?Thursday, May 21, 2015
Genentech is a biotech company based in South San Francisco, Ca., and is a member of the Roche Group. The company has the distinction of having two medicines being used for the treatment of diabetic retinopathy. One of these drugs, Lucentis (ranibizumab), was approved back in February to be used in the treatment of diabetes retinopathy for patients with diabetic macular edema (DME). Lucentis is also indicated for the treatment of patients with wet age-related macular degeneration, and macular edema following retinal vein occlusion. This drug was specifcally designed to treat eye diseases and conditions. [Editor's note: Sam wrote about Lucentis a couple of months ago, and interested readers can go here to learn more about the drug.]
Genentech's other drug is Avastin (Bevacizumab).This drug was developed to treat various types of cancer and it is FDA-approved to treat the following: colorectal cancer, lung cancer, metastatic breast cancer, glioblastoma and metastatic renal cell carcinoma. And it is also being studied to treat liver, ovarian, pancreatic and prostate cancers. Avastin is not FDA approved for the treatment of diabetic retinopathy; and therefore, must be used off-label by healthcare providers. Using medicines off-label means the FDA did not state or intend to use it in the manner it is being used. It is legal for healthcare providers to treat patients with medicines off-label and is commonly carried out by them.
The challenge for healthcare providers for using Avastin for treating eye diseases is a bit of a double-edged sword: using it off-label may be seen as problematic without proper dosing instructions, and yet, Avastin is cheaper than Lucentis.
Avastin's off-label use for eye-related diseases and conditions was discovered by an ophthalmologist several years ago. Avastin is being used off-label in the retinal specialist community to treat retinopathy of prematurity, branch retinal vein occlusion, uveitic macular edema, macular degeneration, and neovascular glaucoma. In addition, Avastin is being used as a presurgical adjunct treatment for diabetic vitreous hemorrhage to reduce bleeding and facilitate membrane peeling.
Lucentis and Avastin's mechanisms of action work by stopping the growth of new blood vessels. Both are injected directly into the eye to target macular degeneration and proliferative diabetic retinopathy. Chemically, Lucentis and Avastin are very similar. Lucentis is a small fragment of the Avastin molecule. To be effective, the drugs must penetrate the tiny vessels of the retina. Avastin is delivered as an intravitreal injection. When injected directly into the eye, Avastin has been reported to totally reverse early-stage diabetic retinopathy in only three weeks.
Studies comparing treatment with Avastin vs. photocoagulation (another treatment for people with DR) showed that patients with macular degeneration:
- Larger reduction in central subfield thickness in Avastin treatment vs. photocoagulation
- One line better visual acuity in Avastin treatment vs. photocoagulation
Avastin is proposed to be used by providers only after laser and steroids therapy have failed or if patients are not candidates for these therapies. The typical injected dose ranges from 1.25 mg in 0.05 ml or 2.50 mg in 0.1 ml.
The increase in intraocular pressure (IOP) is an adverse effect that has been reported for patients on Avastin who receive multiple injections. In some cases, a rise of IOP is from 12 mmHg to 40 mmHg which may last days to weeks and may require multiple medications or surgery to lower IOP. This adverse effect occurs more often in patients with a history of or have baseline glaucoma.
Other risks with intravitreal eye injections include:
- The possibility of an eye infection (endophthalmitis)
- Glaucoma (increased pressure in the eye)
- Cataract formation (blurred vision due to clouding of the lens of the eye)
- Retinal detachment (floaters, shadow, reduced vision)
While many providers who are using Avastin report the medication is cheaper, there is no treatment guidelines about dosing, dosing frequency, and duration of therapy. Another question that remains is whether Avastin is just as safe and effective as lucentis. Moreover, providers reported that they observed that Avastin works well initially but the effect wears off, and there is no information about re-dosing the medication when this occurs.
Avastin’s manufacturer, Genentech, has no plans to find out because its drug Lucentis already received FDA approval for macular degeneration treatment. Therefore, Genentech officials say they have no intention of also funding clinical trials for Avastin to treat eye diseases. Instead, officials from the National Eye Institute (NEI) announced many years ago that they would pay for trials to compare the effectiveness and safety of the two drugs as treatment for macular degeneration
For providers who are continuing to use Avastin off-label to treat macular degeneration, it is recommended to watch IOP fluctuations more closely both in the acute and chronic phase. Also, in patients who have glaucoma and are receiving any type of intravitreal injections, IOP fluctuations should be monitored as well.
Avastin injections may not be a long-term solution; and therefore, other treatments for this condition, including panretinal photocoagulation and/or glaucoma surgery, should be considered. For many providers, Avastin allows them to buy time until eye surgery is needed.
Still, additional studies need to be completed in order to establish safe and effective dosing guidelines for Avastin.