Genentech Statement on Two-Year Protocol T Trial Data in Ophthalmology

South San Francisco, CA — February 27th, 2016 — Protocol T Two-Year Results Published Today

• Two-year visual acuity data showed no statistically significant difference in mean vision gains between 0.3mg Lucentis® (ranibizumab injection) and 2.0mg aflibercept for all three pre-specified patient groups studied in Protocol T (overall, better, and worse vision groups)
• The median number of 15 injections given over two years was the same for Lucentis and aflibercept

 

The two-year results of the Diabetic Retinopathy Clinical Research Network’s (DRCR.net) Comparative Effectiveness Protocol T Study were published today in Ophthalmology. 


The study compared the efficacy and safety of Lucentis, aflibercept and bevacizumab to improve vision or visual acuity (VA) in people with diabetic macular edema (DME) based on the number of letters that are accurately seen on an eye chart. The primary study outcome, mean change in visual acuity at one year, was previously published in March 2015. (N Engl J Med 2015; 372:1193-1203 Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema.). A secondary and the final study endpoint at two years was chosen to determine if visual gains were sustained over two years, and whether there were differences in frequency of intravitreal injection or laser.

At year two, no statistically significant difference in mean change in visual acuity between Lucentis and aflibercept patients was observed in any pre-specified patient groups studied (overall, worse baseline vision (20/50 or worse) or better baseline vision (20/32 to 20/40)). The statistical difference observed at one year for aflibercept vs. Lucentis was no longer observed at year two with respect to the worse seeing group.

The median number of 15 injections given over the two years was the same for Lucentis and aflibercept.

The percentages of serious adverse events reported and of participants hospitalized within two years were similar across the three treatment groups. The data show an imbalance in Antiplatelet Trialists’ Collaboration (APTC) events for patients in the Lucentis arm. The study’s authors noted, "These findings have not been demonstrated consistently in previously reported clinical trials" and added, "the inconsistencies in the totality of the evidence create uncertainty as to whether there is a true increased risk of APTC events with ranibizumab at this time."

"These long-term outcomes are important when studying treatments for patients with a chronic disease like DME," said Jason Ehrlich, MD, PhD, Global Head of Ophthalmology Clinical Science at Genentech. "We are pleased that no statistical differences in vision outcomes or number of injections given at two years were seen when comparing Lucentis and aflibercept in all three pre-specified, Protocol T patient groups."

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 complex retinal diseases, Lucentis continues to be an important treatment choice for physicians and patients.

The full study results can be found in the February 27, 2016 publication of Ophthalmology. Wells JA et al. for the Diabetic Retinopathy Clinical Research Network. “Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-year Results from a Comparative Effectiveness Randomized Clinical Trial.” Ophthalmology, February 27, 2016.

LUCENTIS DOSAGE
 
LUCENTIS^® (ranibizumab injection) is indicated for the treatment of patients with diabetic macular edema (DME).

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).
 

IMPORTANT SAFETY INFORMATION

LUCENTIS is contraindicated in patients with ocular or periocular infections or hypersensitivity to ranibizumab or any of the excipients in LUCENTIS.

WARNINGS AND PRECAUTIONS

Intravitreal injections, including those with LUCENTIS, have been associated with endophthalmitis, retinal detachment, and iatrogenic traumatic cataract. Proper aseptic injection technique should always be utilized when administering LUCENTIS. Patients should be monitored following the injection to permit early treatment, should an infection occur.
Increases in intraocular pressure (IOP) have been noted both pre-injection and post-injection (at 60 minutes) with LUCENTIS. IOP and perfusion of the optic nerve head should be monitored and managed appropriately.

Although there was a low rate of arterial thromboembolic events (ATEs) observed in the LUCENTIS clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).

Fatal events occurred more frequently in DME patients treated monthly with LUCENTIS compared with control. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded.

ADVERSE EVENTS

Serious adverse events related to the injection procedure that occurred in <0.1% of intravitreal injections included endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.

In clinical trials in diabetic macular edema, the most common ocular side effects included conjunctival hemorrhage, cataract, increased IOP, and vitreous detachment. The most common non-ocular side effects included nasopharyngitis, anemia, and nausea.

For additional safety information, please see LUCENTIS full prescribing information at http://`www.LUCENTIS.com.


AVASTIN IMPORTANT SAFETY INFORMATION

Avastin is approved for:

• Metastatic colorectal cancer (mCRC) for first- or second-line treatment in combination with intravenous 5-fluorouracil–based chemotherapy. It is also approved to treat mCRC for second-line treatment when used with fluoropyrimidine-based (combined with irinotecan or oxaliplatin) chemotherapy after cancer progresses following a first-line treatment that includes Avastin
  
  • Avastin is not approved for use after the primary treatment of colon cancer that has not spread to other parts of the body
• Advanced nonsquamous non–small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel in people who have not received chemotherapy for their advanced disease
• Metastatic kidney cancer (mRCC) when used with interferon alfa
• Advanced cervical cancer (CC) in combination with paclitaxel and cisplatin or paclitaxel and topotecan is approved to treat persistent, recurrent, or metastatic cancer of the cervix
• Platinum resistant ovarian cancer (prOC) in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan, is approved to treat platinumresistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer in women who received no more than two prior chemotherapy treatments.
  
  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 (up to 3.2) 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.

Additional serious adverse events
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 in the body (GI and non-GI fistula formation) was seen in up to 2% of people in metastatic colorectal cancer and ovarian cancer patients. In a study of patients with cervical cancer, formation of an abnormal passage between the vagina and GI tract was seen in 8.3 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 ≤1 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 blood clots (VTE), up to 10.6 percent
  • severe to life threatening high blood pressure, which was seen in 5 percent to 18 percent of people
  • nervous system and vision disturbances (Posterior Reversible Encephalopathy 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 could cause a woman’s ovaries to stop working and may impair her ability to have children.
• Avastin should not be used in ovarian cancer patients who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction

 

Patients who are pregnant, think they 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 six months following the last dose of Avastin. Avastin can cause fertility issues for women.

Women should be advised that breastfeeding while on Avastin is may harm the baby and is therefore not recommended.

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.

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

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 more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and 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.