Genentech Statement on Protocol T Trial Data in the New England Journal of Medicine

The Diabetic Retinopathy Clinical Research Network’s (DRCR.net) Comparative Effectiveness Protocol T Study was published today in the New England Journal of Medicine.

The study compared the safety and efficacy of Lucentis® (ranibizumab), aflibercept and bevacizumab to improve the visual sharpness or clearness (visual acuity) in people with diabetic macular edema (DME) based on the number of letters that are accurately seen on a visual eye chart, adding to the body of evidence of clinical trials of anti-VEGF treatments in DME. 

 

People with DME receiving Lucentis PRN (Pro Re Nata or as needed) showed significant improvement in visual sharpness with a gain of more than two lines of vision (11 letters), and only a difference of two letters when compared to aflibercept (13 letters) in the overall study population (baseline visual acuity ranged from 20/32-20/50; Lucentis N=206; aflibercept N=208). According to the study authors, there was no difference between the medicines when vision loss was mild (baseline visual acuity of 20/32 or 20/40). A 4.7 letter difference was observed with a baseline visual acuity of 20/50 or worse (Lucentis 14.2 letters; aflibercept 18.9 letters). Genentech looks forward to better understanding the full one-year Protocol T data and whether differences in baseline characteristics influenced study results particularly in patients with worse vision.

 

There were no differences in rates of serious adverse events, deaths, hospitalizations, and no major cardiovascular events were identified among the treatment groups in pre-specified endpoints. Out of the many safety comparisons conducted, a single post-hoc analysis showed an imbalance in the Lucentis arm in a broad, atypical grouping of vascular and cardiovascular terms called “Any Cardiovascular Event.” However, the authors identified this result as inconsistent with prior studies of Lucentis and said it “may be due to chance.”

 

Based on an additional post-hoc analysis from pivotal studies with Lucentis, we did not find an increased risk of cardiovascular events when compared to placebo (sham) treatment. We do not believe this is a new safety issue with Lucentis for patients with DME at this time.  

 

For more than 14 years, Lucentis safety and efficacy has been studied in more than 9,080 patients, across eight pivotal and 21 clinical trials, lasting up to five years in wet age-related macular degeneration (AMD), macular edema after retinal vein occlusion (RVO), DME and diabetic retinopathy in people with DME.

 

Based on the totality of evidence in support of its efficacy and well-characterized safety profile as well as the depth and breadth of clinical experience in treating these complex retinal diseases, Genentech believes Lucentis is an important treatment choice for physicians and patients.

 

The full study results can be found in the February 19, 2015 publication of the New England Journal of Medicine. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema. N Engl J Med 2015; Vol. 372 No. 8. 

LUCENTIS DOSAGE AND ADMINISTRATION

 

Lucentis is indicated for the treatment of patients with: 


Neovascular (Wet) Age-Related Macular Degeneration (AMD) 

Macular Edema Following Retinal Vein Occlusion (RVO) 

Diabetic Macular Edema (DME)

Diabetic Retinopathy (DR)

 

Neovascular (Wet) Age-Related Macular Degeneration (AMD) 

LUCENTIS 0.5 mg (0.05 mL) is recommended to be administered by intravitreal injection once a month (approximately 28 days).

 

Although not as effective, patients may be treated with 3 monthly doses followed by less frequent dosing with regular assessment. In the nine months after 3 initial monthly doses, less frequent dosing with 4-5 doses on average is expected to maintain visual acuity while monthly dosing may be expected to result in an additional average 1-2 letter gain. Patients should be assessed regularly.

 

Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses. Compared with continued monthly dosing, dosing every 3 months over the next 9 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average. Patients should be assessed regularly.

 

Diabetic Macular Edema (DME) 

LUCENTIS 0.3 mg (0.05 mL) is recommended to be administered by intravitreal injection once a month (approximately 28 days).

 

Macular Edema Following Retinal Vein Occlusion (RVO) 

LUCENTIS 0.5 mg (0.05 mL) is recommended to be administered by intravitreal injection once a month (approximately 28 days). In the RVO clinical studies, patients received monthly injections of LUCENTIS for 6 months. In spite of being guided by optical coherence tomography and visual acuity re-treatment criteria, patients who were then not treated at month 6 experienced on average, a loss of visual acuity at month 7, whereas patients who were treated at month 6 did not. Patients should be treated monthly.

 

Diabetic Retinopathy (DR) with DME

LUCENTIS 0.3 mg (0.05 mL of 6 mg/mL LUCENTIS solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).

 

 

 

LUCENTIS IMPORTANT SAFETY INFORMATION 

 

Patients should not use Lucentis if they have an infection in or around the eye or are allergic to Lucentis or any of its ingredients. Lucentis is a prescription medication given by injection into the eye and it has side effects. Some Lucentis patients have had detached retinas and serious infections inside the eye. 

 

Uncommonly, Lucentis patients have had serious, sometimes fatal problems related to blood clots, such as heart attacks or strokes.

 

Some patients have had increased eye pressure before and within one hour of an injection.

 

Serious side effects include inflammation inside the eye and, rarely, problems related to the injection procedure such as cataracts. These side effects can make vision worse.

 

The most common eye-related side effects are increased redness in the white of the eye, eye pain, small specks in vision and increased eye pressure. The most common non-eye-related side effects are nose and throat infections, headache, lung/airway infections, and nausea.

 

If the eye becomes red, sensitive to light, or painful, or if there is a change in vision, patients should call or visit an eye doctor right away.

 

Lucentis is for prescription use only.

 

For additional safety information, please see Lucentis full prescribing information, available here: http://www.gene.com/download/pdf/lucentis_prescribing.pdf

 

AVASTIN INDICATIONS 

 

Avastin is not approved for intravitreal (ITV) use in the eye by the FDA.  

 

Avastin is currently approved by the FDA for the following indications: 

•Metastatic colorectal cancer (MCRC): Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil–based chemotherapy. Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen. Avastin is not indicated for adjuvant treatment of colon cancer.

•Non-squamous non-small cell lung cancer (NSCLC): Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer in combination with carboplatin and paclitaxel.

•Metastatic renal cell carcinoma (mRCC): Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

•Cervical Cancer: Avastin is approved in combination with paclitaxel and cisplatin or paclitaxel and topotecan for treatment of women with persistent, recurrent or metastatic carcinoma of the cervix.  

•Ovarian Cancer: Avastin is approved in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan for the treatment of women with platinum-resistant, recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer, who received no more than two prior chemotherapy regimens.

 

 

Avastin BOXED WARNINGS and Additional Important Safety Information
People receiving Avastin may experience side effects. In clinical trials, some people treated with Avastin experienced serious and sometimes fatal side effects, including: 

 

Gastrointestinal (GI) perforation: Treatment with Avastin can result in the development of a serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine, or large intestine. In clinical trials, this event occurred in more people who received Avastin than in the comparison group (3.2 percent to 0.3 percent). In some cases, GI perforation resulted in fatality. Avastin therapy should be permanently stopped if GI perforation occurs. 

 

Surgery and wound healing problems: Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases, this event resulted in fatality. Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. In a controlled clinical trial, in patients with metastatic colorectal cancer who had surgery during the course of treatment, the incidence of wound healing complications, including serious and fatal complications, was 15 percent for patients who received Avastin and four percent for patients who did not receive Avastin. 

 

Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of wound healing problems following surgery has not been determined. Treatment with Avastin should be stopped at least 28 days before voluntary surgery and in people with wound healing problems following surgery that require medical treatment. Treatment with Avastin should be stopped in patients with slow or incomplete wound healing.  

 

Severe bleeding: Treatment with Avastin can result in serious or fatal bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds and vaginal bleeding. These events occurred up to five times more often in people who received Avastin compared to patients who received only chemotherapy. Across cancer types, 0.4 percent to 6.9 percent of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin. Treatment with Avastin should be permanently stopped if serious bleeding occurs. 

 

In clinical trials for different cancer types, there were additional serious and sometimes fatal side effects that occurred in more people who received Avastin than in those in the comparison group. The formation of an abnormal passage from parts of the body to another part (non-GI fistula formation) was seen in less than 1 percent of people. Severe to life-threatening stroke or heart problems were seen in 2.6 percent of people. Too much protein in the urine that led to kidney problems was seen in less than one percent of people. Additional serious side effects that occurred in more people who received Avastin than those in the comparison group included severe to life-threatening high blood pressure, which was seen in five percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.5 percent of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than three percent of people, and severe reactions occurred in 0.2 percent of people. Avastin can cause fertility issues for women. Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children.

 

Common side effects that occurred in more than 10 percent of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain, and inflammation of the skin (exfoliative dermatitis). Across all trials, treatment with Avastin was permanently stopped in 8.4 percent to 21 percent of people because of side effects. 

 

Patients who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risk of loss of the pregnancy or the potential risk of Avastin to the fetus during and following Avastin therapy, and the need to continue an effective birth control method for at least six months following the last dose of Avastin. 

 

Women should be advised to discontinue nursing or discontinue treatment with Avastin, taking into account the importance of Avastin to the mother.

 

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch.   

Patients and caregivers may also report side effects to Genentech at (888) 835-2555.

 

For full Prescribing Information and Boxed WARNINGS on Avastin, please visit http://www.avastin.com.

 

 

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About Genentech

Founded 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.