Two Pivotal Phase III Lucentis Studies Showed Patients With Diabetic Macular Edema Experienced Significant Improvements in Vision and Fewer Developed More Advanced Retinopathy

SAN DIEGO--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced 24-month results from the two pivotal Phase III trials (RISE and RIDE) assessing the efficacy and safety of Lucentis^® (ranibizumab injection) in people with diabetic macular edema (DME). The data showed patients who received Lucentisexperienced significant, rapid and sustained improvement in vision compared to those who received placebo (sham) injections. Additional analyses showed patients who received Lucentis were significantly more likely to achieve 20/40 vision*and experience less progression of the underlying diabetic retinopathy disease.

“The data are promising for patients with diabetes because there are currently no FDA-approved medicines to treat this debilitating eye condition”

[*A person with 20/40 vision would need to be just 20 feet closer to an eye chart to see it with the same visual acuity as an individual with 20/20, which is considered normal vision based on standard eye chart measures.¹ Vision less than 20/40 disqualifies a person from obtaining a driver’s license in many states.²]

The safety results were consistent with previous studies and no new adverse events related to Lucentis were observed.

DME is swelling of the retina that occurs in people with diabetes, who suffer from a complication called diabetic retinopathy. Diabetic retinopathy is the most common diabetic eye disease and is characterized by damage to the blood vessels of the retina, the nerve layer at the back of the eye.³DME can cause blurred vision, severe vision loss and blindness.³Up to 10 percent of people with diabetes, or more than 2 million Americans, will develop DME during their lifetime.⁴

“The data are promising for patients with diabetes because there are currently no FDA-approved medicines to treat this debilitating eye condition,” said David S. Boyer, M.D. of Retina-Vitreous Associates Medical Group in Los Angeles, who presented the results today in a Late Breaking Clinical Trial session at the American Diabetes Association 71^st Scientific Sessions. “These studies showed that Lucentis helped improve vision even in patients without tight glucose control, and fewer patients who received Lucentis progressed to more advanced stages of diabetic retinopathy.”

It was announced previously that both the RISE and RIDE studies met their primary endpoints, demonstrating that after 24 months, a significantly greater number of patients who received Lucentis were able to read at least 15 additional letters (three lines) on the eye chart than they could at the start of the study. A preplanned subgroup analysis reported today indicated the improvements were generally similar for patients with well-controlled glucose (baseline HbA1c ≤ 8) and poorly controlled glucose (baseline HbA1c >8).

Additionally, in both studies, significantly more patients who received Lucentis compared with sham injections:

Experienced improvements in average eye chart reading scores starting at seven days post first injection, which were sustained at 24 months;
Achieved vision greater than or equal to 20/40;
Were less likely to progress to more advanced (proliferative) diabetic retinopathy; and
Experienced decreased retinal swelling (central foveal thickness).

Impaired vision can impact day-to-day functioning and quality of life. In both the RISE and RIDE studies, patients who received Lucentis reported greater improvements in their ability to perform vision-related daily activities such as reading and driving, compared to the sham group, based on composite responses to the National Eye Institute Visual Functioning Questionnaire-25.

Genentech plans to file a supplemental biologics license application (sBLA) with the U.S. Food & Drug Administration (FDA) for Lucentis in DME later this year.

Study Results

In the studies, changes in vision were measured by best-corrected visual acuity (BCVA), which is the best possible vision a person can achieve with corrective lenses, based on reading a standardized eye chart. Key endpoint data presented included:

MONTH 24 OUTCOMES	RISE			RIDE
MONTH 24 OUTCOMES	Sham	Lucentis 0.3 mg	Lucentis 0.5 mg	Sham	Lucentis 0.3 mg	Lucentis 0.5 mg
Percent of patients able to read at least 15 additional letters (3 lines) on eye chart compared to baseline (primary endpoint)	18.1	44.8	39.2	12.3	33.6	45.7
Percent of patients meeting primary endpoint with better controlled glucose at baseline (HbA1c ≤ 8); RISE: n=243; RIDE: n=246	17.5	46.9	39.0	13.1	36.7	49.4
Percent of patients meeting primary endpoint with less controlled glucose at baseline (HbA1c >8); RISE: n=120; RIDE: n=122	18.6	43.6	42.1	12.2	29.3	40.0
Percent of patients able to achieve vision ≥ 20/40	37.8	60.0	63.2	34.6	54.4	62.2
Percent of patients who progressed to proliferative diabetic retinopathy	15.0	1.6	5.6	11.5	3.2	3.9

RISE and RIDE Safety

An analysis of the 24-month data from the RISE and RIDE studies showed an ocular and systemic safety profile consistent with previous Lucentis Phase III trials.

In the studies, patients who received Lucentis experienced fewer adverse events associated with diabetic retinopathy, including abnormal growth of new blood vessels inside the eye (retinal neovascularization; RISE: 13.8 percent of patients in the sham injection group vs. 0.8 percent in the 0.3 mg Lucentis dose group and 4.0 percent in the 0.5 mg Lucentis dose group; RIDE: 5.5 percent of patients in the sham injection group vs. 0.8 percent in each of the Lucentis dose groups) and bleeding inside the eye (vitreous hemorrhage; RISE: 13.0 percent of patients in the sham injection group vs. 3.2 percent in each of the Lucentis dose groups; RIDE: 15.0 percent in the sham injection group vs. 0.8 percent in the 0.3 mg Lucentis dose group and 2.4 percent in the 0.5 mg Lucentis dose group).

The incidence of serious adverse events occurring in the study eye in Lucentis-treated patients was low and often procedure-related. Study eye serious adverse events included traumatic cataracts (RISE: 0 percent of sham injection patients vs. 0.8 percent of patients in the combined Lucentis groups; RIDE: 0 percent of sham patients vs. 0.4 percent in the combined Lucentis groups), bacterial infection inside the eye (endophthalmitis; RISE: 0 percent of sham patients vs. 0.4 percent in the combined Lucentis groups; RIDE: 0 percent of sham patients vs. 1.2 percent in the combined Lucentis groups), increased intraocular pressure (RISE: 0 percent of all groups; RIDE: 0 percent of sham injection patients vs. 0.4 percent of patients in the combined Lucentis groups), retinal detachment (RISE: 0.8 percent of sham injection patients vs. 0 percent in the combined Lucentis groups; RIDE: 0 percent of sham injection patients vs. 0.4 percent in the combined Lucentis groups), and inflammation inside the eye (uveitis; RISE: 0 percent of all groups; RIDE: 0 percent of sham injection patients vs. 0.4 percent in the combined Lucentis groups).

The analysis indicates no new findings related to non-ocular or systemic safety. The overall rates of serious adverse events potentially related to systemic VEGF inhibition appears similar among treatment groups (RISE: 10.6 percent of patients in the sham injection group vs. 5.6 percent in the 0.3 mg Lucentis dose group and 11.9 percent in the 0.5 mg Lucentis dose group; RIDE: 9.4 percent of patients in the sham injection group vs. 9.6 percent in the 0.3 mg Lucentis dose group and 5.6 percent in the 0.5 mg Lucentis dose group).

Among non-ocular serious adverse events in the RISE and RIDE studies were strokes (RISE: 1.6 percent of patients in the sham injection group vs. 0.8 percent in the 0.3 mg Lucentis dose group and 4.0 percent in the 0.5 mg Lucentis dose group; RIDE: 1.6 percent of patients in the sham injection group vs. 1.6 percent in the 0.3 mg Lucentis dose group and 2.4 percent in the 0.5 mg Lucentis dose group) and heart attack (RISE: 2.4 percent of patients in the sham injection group vs. 1.6 percent in the 0.3 mg Lucentis dose group and 3.2 percent in the 0.5 mg Lucentis dose group; RIDE: 4.7 percent of patients in the sham injection group vs. 5.6 percent in the 0.3 mg Lucentis dose group and 2.4 percent in the 0.5 mg Lucentis dose group).

In RISE, one patient in the sham injection group, three patients in the 0.3 mg Lucentis dose group and five patients in the 0.5 mg Lucentis dose group died during the study. Three of the eight deaths in the Lucentis dose groups were from non-vascular causes. In RIDE, two patients in the sham injection group, four patients in the 0.3 mg Lucentis dose group and six patients in the 0.5 mg Lucentis dose group died during the study. Three of the six deaths in the 0.5 mg Lucentis dose group were from non-vascular causes.

About RISE and RIDE

RISE and RIDE are multicenter, randomized, double-masked, sham injection-controlled, 36-month (sham injection-controlled for 24 months) Phase III studies designed to assess the efficacy and safety of Lucentis in patients with DME (RISE n=377; RIDE n=382). Patients were randomized to receive monthly injections of either 0.3 mg Lucentis (RISE n=125; RIDE n=125), 0.5 mg Lucentis (RISE n=125; RIDE n=127) or monthly sham injections (RISE n=127; RIDE n=130). The studies were not designed to compare the two doses of Lucentis, but each dose against the sham injection group.

Beginning at three months, macular laser rescue treatment was made available to all patients, if needed, based on pre-specified criteria. Panretinal laser treatment was available to all patients as clinically indicated. After month 24, patients in the sham injection group were eligible to receive monthly injections of 0.5 mg Lucentis and all patients will continue to be followed and dosed monthly for a total of 36 months. The study then continues in an open-label extension phase.

RISE and RIDE are two identical, parallel confirmatory studies designed to support application to the FDA for a potential new indication for Lucentis for DME.

About DME

In DME, damaged blood vessels leak fluid into the central portion of the retina, called the macula, causing it to swell. The macula is the part of the eye responsible for sharp central vision.³ The fovea is at the center of the macula. DME can occur in patients with type 1 or type 2 diabetes.³

Approximately 26 million people in the United States have diabetes and 1.9 million new cases are diagnosed in people aged 20 and older each year.⁵ Up to 75,000 new cases of DME are estimated to develop each year.⁴ DME is a leading cause of blindness among the working-age population in most developed countries.⁶

The current standard of care for DME is laser surgery that helps seal the leaky blood vessels to slow the leakage of fluid and reduce the amount of fluid in the retina.^3,7

About Lucentis

Lucentis is a vascular endothelial growth factor (VEGF) inhibitor which was first approved by the FDA for the treatment of neovascular (wet) age-related macular degeneration (AMD) in June 2006. Lucentis was also approved by the FDA for macular edema following retinal vein occlusion (RVO) on June 22, 2010. Lucentis was approved in 2011 for treatment of visual impairment due to macular edema following RVO and for treatment of visual impairment due to DME in Europe, where it is marketed by Novartis.

Lucentis is designed to bind to and inhibit VEGF, a protein that is believed to play a critical role in the formation of new blood vessels (angiogenesis) and the hyperpermeability (leakiness) of the vessels. In wet AMD, these blood vessels grow under the retina and leak blood and fluid, causing rapid damage to the macula. In RVO, angiogenesis and hyperpermeability can lead to macular edema, the swelling and thickening of the macula.

In wet AMD clinical trials, Lucentis administered monthly demonstrated an improvement in vision of three lines or more on the study eye chart in up to 41 percent of patients at two years. Nearly all patients (90 percent) treated monthly with Lucentis in those trials maintained vision.

In two Phase III clinical trials studying macular edema following RVO, both studies showed that Lucentis administered monthly demonstrated an early (day seven) and sustained vision improvement of three lines or more on the study eye chart during the six-month controlled treatment period of the studies.

Lucentis Safety

Lucentis is a prescription medication given by injection into the eye, and it has side effects. Lucentis is not for everyone. Lucentis should not be used in patients who have an infection in or around the eye or are allergic to Lucentis or any of its ingredients.

Some Lucentis patients have serious side effects related to the injection. These include serious infections inside the eye, detached retinas, and cataracts. Other uncommon serious side effects include inflammation inside the eye and increased eye pressure. These can make a patient’s vision worse. Some patients have increases in eye pressure within one hour of an injection. A patient’s eye doctor should check the eye pressure and eye health during the week after a Lucentis injection.

Although not common, Lucentis patients have had eye- and non–eye-related blood clots (heart attacks, strokes, and death). If a patient’s eye becomes red, sensitive to light, painful, or there is a change in vision, patients should call or visit their eye doctor right away.

The most common side effects to the eye are increased redness in the whites of the eye, eye pain, small specks in vision, the feeling that something is in the eye. The most common non–eye-related side effects are nose and throat infections, headache, and respiratory (lung) infections.

Lucentis is for prescription use only.

Please visit http://www.lucentis.com for the Lucentis full prescribing information, and additional important safety information.

Lucentis was discovered by Genentech and is being developed by Genentech and Novartis for diseases or disorders of the eye. Genentech retains commercial rights in the U.S. and Novartis has exclusive commercial rights for the rest of the world.

About Genentech

Founded more than 30 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.

References:

¹American Optometry Association: Comprehensive Eye and Vision Examination, Visual Acuity. Available at: http://www.aoa.org/eye-exams.xml

²National Eye Institute. National Plan for Eye and Vision Research. Available at: http://www.nei.nih.gov/strategicplanning/np_low.asp

³National Eye Institute. Health Information. Available at: http://www.nei.nih.gov/health/diabetic/retinopathy.asp.

⁴Ali, F.A. A review of diabetic macular edema. Digital Journal of Ophthalmology, vol. 3, no. 6, 1997. Available at: http://www.djo.harvard.edu/site.php?url=/physicians/oa/387.

⁵American Diabetes Association. Statistics. Available at: http://www.diabetes.org/diabetes-statistics.jsp.

⁶Ciulla TF, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening and novel therapies. Diabetes Care. 2003;26:2653-2664.

⁷Macular Edema, Diabetic; emedicine from WebMD, Medscape Specialists: Ophthalmology/Retina; Updated: Oct 7, 2010. Available at: http://emedicine.medscape.com/article/1224138-overview.