On September 16, 2014 Regeneron Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has granted EYLEA (aflibercept) Injection Breakthrough Therapy designation for the treatment of diabetic retinopathy in patients with diabetic macular edema (DME) (Press release Regeneron, SEP 16, 2014, View Source [SID:1234500753]). The designation is based on positive results in two Phase 3 trials (VIVID-DME and VISTA-DME), in which EYLEA demonstrated a statistically significant improvement in a pre-specified measure of diabetic retinopathy in patients with DME after two years of treatment.

“Millions of people in the U.S. are living with diabetic eye diseases that can cause vision loss and even blindness,” said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. “There are no FDA-approved medicines for diabetic retinopathy and we look forward to working closely with the FDA to potentially bring EYLEA to these patients as soon as possible. We plan to submit a supplemental Biologics License Application (sBLA) in the U.S. for diabetic retinoapthy in patients with DME later this year.”

In the Phase 3 VIVID-DME trial in diabetic retinopathy patients with DME, 29 percent of evaluable patients in the 2Q4 group (monthly) and 33 percent of evaluable patients in the 2Q8 group (every two months, after 5 initial monthly injections) treated with EYLEA experienced at least a 2-step improvement on the diabetic retinopathy severity scale (DRSS), a grading system measuring the degree of retinopathy, compared to 8 percent of patients in the laser control group (p less than 0.001). In the Phase 3 VISTA-DME trial in diabetic retinopathy patients with DME, 40 percent of evaluable patients in both the 2Q4 and 2Q8 groups treated with EYLEA experienced at least a 2-step improvement on the DRSS compared to 17 percent of patients in the laser control group (p less than 0.0001). The most frequent ocular adverse events (AEs) observed in the VIVID-DME trial were conjunctival hemorrhage, cataract, and increased intraocular pressure. The most frequent ocular AEs observed in the VISTA-DME trial were conjunctival hemorrhage, eye pain, and vitreous floaters. The two-year results from these trials on the primary endpoint of best-corrected visual acuity (BCVA) and overall safety have been previously announced and are available here.

The Breakthrough Therapy designation was created by the FDA to expedite the development and review of drugs for serious or life-threatening conditions. Drugs qualifying for this designation must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy. The designation includes all of the fast track program features, as well as more intensive FDA guidance and discussion. The Breakthrough Therapy designation is distinct from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met.

EYLEA is approved in the United States, European Union (EU) and other countries for the treatment of wet age-related macular degeneration (AMD), macular edema following central retinal vein occlusion (CRVO), and DME. Regulatory submissions have been made for EYLEA in the U.S. and EU for macular edema following branch retinal vein occlusion (BRVO).

About Diabetic Retinopathy and Diabetic Macular Edema (DME)
Diabetic retinopathy is a common complication of diabetes, causing damage to the retina, which may lead to poor vision and vision loss. Over time, patients with diabetic retinopathy are at risk of experiencing vision-threatening events. These include DME, which refers to the swelling of the macula (the part of the retina responsible for central, fine vision) and progression to proliferative diabetic retinopathy, which often results in profound visual loss due to associated complications including vitreous hemorrhage and/or tractional retinal detachment. DME is the most frequent cause of vision loss in patients with diabetes and eventually can lead to blindness.1,2 It is estimated that of the 29.1 million American adults living with diabetes, 7.7 million have diabetic retinopathy, 1.5 million have been diagnosed with DME and approximately another million cases of DME are undiagnosed.3,4,5 Diabetic retinopathy and DME occur when blood vessels in the retina are damaged by chronic high blood sugar levels caused by diabetes.

Vascular endothelial growth factor (VEGF), a naturally occurring family of growth factors in the body, appears to play a critical role in the development of DME.

On September 16, 2014 Northwest Biotherapeutics reported that its DCVax-L is the first product to receive formal designation as a “Promising Innovative Medicine” (PIM) under the new “Early Access to Medicines Scheme” (EAMS) launched in the UK in April 2014 (Press release Northwest Biotherapeutics, SEP 16, 2014, View Source [SID:1234500752]). A PIM is the first step in a 2-step process for early access approval under the EAMS.

The PIM designation for DCVax-L covers all malignant gliomas, which would include both Glioblastoma multiforme (the most severe grade) as well as less malignant grades, and would include both newly diagnosed and recurrent gliomas.

The EAMS is an important new initiative in the UK, launched by the Medicines and Healthcare Products Regulatory Agency (MHRA, the FDA of the UK), to lead the way in accelerating patients’ access to innovative new medicines for serious diseases. Information about the EAMS program can be found on the MHRA website at: View Source

The first step under the EAMS is MHRA’s scientific evaluation of whether a product candidate meets three criteria for a PIM designation: (i) the product is for a serious disease or condition with high unmet medical need; (ii) the product is likely to offer a major advantage over treatments available today; and (iii) the potential adverse effects of the product are outweighed by the potential benefits.

NW Bio’s DCVax-L has now become the first product to earn this PIM certification. There is no expiration on the PIM certification.

The second step under the EAMS is MHRA’s determination of a Scientific Opinion about the product candidate’s benefits and risks, based on available clinical data. A positive or negative Scientific Opinion will be judged by the same three criteria as for the PIM designation, as well as a fourth criterion: the Company’s ability to manufacture the product to rigorous “GMP” (clinical grade) standards.

If the Scientific Opinion is positive, the product candidate may then be prescribed by physicians and provided to (and paid for by) patients before the product is formally licensed and while it is still in clinical development.

MHRA aims to deliver the Scientific Opinion within 90 days after a party submits an application for Step 2 of the EAMS process.

In granting the first PIM designation under this new EAMS to DCVax-L, the UK Department Of Health has stated, “An innovative cell therapy for cancer has become the first to be certified as ‘promising’ as part of a new Government scheme aimed at getting new medicines to patients quicker.

The medicine, which has been developed by US-based pharmaceutical company Northwest Biotherapeutics Inc. (NW Bio), is the first drug to be awarded the UK’s new Promising Innovative Medicines (PIM) designation, the initial step in the Early Access to Medicines Scheme which aims to increase patient access to unlicensed treatments.”

UK Life Sciences Minister George Freeman noted that “The designation of the PIM is the first, crucial step in developing cutting-edge medicines sooner, giving real hope to patients and their families.”

Dr. Keyoumars Ashkan, a senior neuro-surgeon at Kings College Hospital in London, and the Principal Investigator for the clinical trial of DCVax-L in the UK, commented that “Brain cancers strike patients of all ages, and are rapidly lethal. New treatment options are urgently needed. DCVax-L offers an exciting new approach to treating these brain cancers, through personalized immune therapy. It is encouraging to see this innovative new product be the first to receive certification as a Promising Innovative Medicine under the new EAMS.”

Linda Powers, CEO of NW Bio, commented that “We are most grateful to the MHRA and Minister Freeman for spearheading this new EAMS. It strikes a very practical balance between clinical benefits and risks, through careful scientific evaluations, and will be of great help to doctors and patients in opening up new treatment options.”

“In prior Phase I/II clinical trials of DCVax-L for brain cancer, significant delays in disease progression and significant extensions of patients’ survival have been seen, with virtually no serious adverse effects,” Ms. Powers continued. “We believe that DCVax-L embodies the combination of innovation and beneficial balance of clinical benefits and risks that the EAMS is designed to accelerate. We are excited that DCVax-L has received the first PIM certification.”