SUBSPECIALTY NEWS

CMS Defends Controversial Reimbursement Plan

Lucentis and Eylea would be most affected.

BY JERRY HELZNER, CONTRIBUTING EDITOR

■ A decision on a so-called “demonstration plan” announced by CMS in March that would reward medical practitioners for administering less-costly drugs and penalize them for using more expensive therapies is expected before the end of the year. The plan has not been withdrawn despite the fact that public comments from the medical community and lawmakers have been overwhelmingly against implementation of such an initiative. CMS Chief Medical Officer Patrick Conway, MD, strongly defended the plan in an appearance before a hostile Senate Finance Committee this summer. Dr. Conway would only say that CMS is continuing to review the more than 1,300 public comments it has received and is considering some modifications that would ensure patients in rural communities access to the drugs they need.

Though the plan — affecting Part B Medicare physician-administered therapies — would not be initially implemented nationwide, CMS says the number of practices affected would be sizable. The greatest impact in ophthalmology would fall on retina specialists who prescribe Lucentis (Genentech) and Eylea (Regeneron). Given the reimbursement formula that has been proposed by CMS, practices would most likely lose money on every injection of those two leading anti-VEGF drugs prescribed for a range of retinal diseases. The current formula of average selling price plus 6% would be reduced to average selling price plus 2.5% plus $16.80 per drug per day, which would not cover the overhead for procuring, storing, administering, tracking, and applying for reimbursement. In a joint letter to CMS disputing the merits of the plan, the AAO, ASRS, and The Retina Society assert that Avastin (Genentech) as the lower-cost alternative anti-VEGF is not interchangeable with Lucentis and Eylea for efficacy, safety, and — as a compounded drug — potential availability reasons.

WHO’S FOR THE DEMO PLAN?

Retinal Physician has learned that though the medical community is overwhelmingly against the demonstration plan, the major “public policy” groups such as AARP, Public Interest, and the Center for Medicare Advocacy are all strongly backing it.

David Lipschutz, JD, managing attorney for the Center for Medicare Advocacy, says his group is for the plan because it will cut Medicare outlays, as well as reduce the power of the pharmaceutical industry.

“We look at this initiative on more of a global basis and don’t get involved with the nuances that may affect each individual specialty or subspecialty,” he says. “If the ophthalmology community can cite some special factors that would make this plan a hardship, it’s up to their representatives to present them. We would be all ears.”

Meanwhile, attorneys who represent ophthalmology practices are advising that their clients prepare for a CMS decision that may not be to their liking.

“The plan may be amended and CMS may make special carve-outs to lessen the impact on certain specialties, but everyone is following this and it’s too much of a political ‘hot-button’ issue to go away,” says David Farber, of King & Spalding, Washington, DC.

Brian Dickerson, an attorney at FisherBroyles in Washington, DC, advises that practitioners must communicate directly with their patients as to any changes in treatment that may arise if the CMS plan is implemented.

“If you are switching to a different drug, you must talk to the patient and tell the patient how the new therapy may be different than what the patient was previously receiving. If it’s Avastin, you must tell the patient that’s it’s an off-label indication and that it is compounded rather than direct from the manufacturer.”

Meanwhile, both Mr. Farber and Mr. Dickerson say that ophthalmologists and their advocates should continue to make their case to their elected representatives as the next few months will be crucial in terms of influencing the CMS decision.

If the demonstration plan goes forward, CMS would introduce additional aspects at a later date, including value-based purchasing tools. However, the change is that reimbursement would still be the cornerstone of the initiative.

Allergan Buys Gene Therapy Pioneer RetroSense

RetroSense has begun clinical trial in RP.

■ Allergan, a leading global pharmaceutical company, and RetroSense Therapeutics LLC,  a private, clinical-stage biotechnology company focused on novel gene therapy approaches to restore vision in patients afflicted with blindness, announced that Allergan has acquired substantially all of the assets of RetroSense in an all-cash transaction. Under the terms of the transaction, Allergan has paid RetroSense a $60 million upfront payment and has agreed to potential regulatory and commercialization milestone payments related to its lead development program, RST-001, a novel gene therapy for the potential treatment of retinitis pigmentosa.

RST-001 is a first-in-class gene therapy application of optogenetics, a therapeutic approach that confers light sensitivity to cells that were not previously, or natively, light sensitive. By applying optogenetics to retinas in which rod and cone photoreceptors have degenerated, the technology introduces additional light sensitivity to the retina. In 2014, RST-001 received an Orphan Drug Designation by the FDA for the treatment of retinitis pigmentosa.

The RST-001 optogenetic approach employs a photosensitivity gene, channelrhodopsin-2, to create new photosensors in retinal ganglion cells to potentially restore vision in retinal degenerative conditions. In August 2015, RetroSense’s Investigational New Drug application for RST-001 received clearance from the FDA. In March 2016, RetroSense initiated a phase 1/2a clinical trial to evaluate the safety of RST-001 in patients being dosed, and in August 2016, the low-dose cohort of patients had been safely dosed.

“The RST-001 program and its optogenetic gene therapy approach could be a real breakthrough in the treatment of unmet needs across a host of retinal conditions, including RP,” said David Nicholson, chief research and development officer,  Allergan. “The team at Allergan is excited by the prospect of advancing an entirely new approach in the treatment of retinal diseases, and this technology is highly complementary to our ongoing development programs in this critical treatment area.”

Jetrea Effective in Two-year Study

Drug meets key endpoints in VMA.

■ The Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) trial was designed to evaluate the long-term efficacy and safety profile of ocriplasmin (Jetrea, ThromboGenics) for the treatment of symptomatic vitreomacular adhesion (VMA) and vitreomacular traction, including full-thickness macular hole (FTMH). Positive results from the 220-patient, phase 3b study are now reported in the journal Ophthalmology.

The OASIS trial met its primary endpoint with pharmacologic VMA resolution at day 28 being significantly higher in the ocriplasmin group (41.7%) compared with the sham group (6.2%). The treatment effect was maintained until study end. In the ocriplasmin group, pharmacologic VMA resolution at day 28 was higher in subgroups with the following baseline characteristics compared with the complementary subgroups without them: presence of focal VMA, presence of FTMH, absence of epiretinal membrane (ERM), and phakic lens status. In the ocriplasmin group, 50.5% of subjects had a ≥2-line improvement in BCVA from baseline compared with 39.1% of subjects in the sham group. The nonsurgical FTMH closure rate was 30.0% for the ocriplasmin group compared with 15.4% for the sham group. All other secondary endpoints also favored ocriplasmin over sham. Regarding safety, most adverse events were mild to moderate, had a short onset time, and were transient, with no new safety signals identified.

The trial involved 12 visits over 24 months. Inclusion criteria included presence of VMA and BCVA of 20/32 or worse in the study eye. Exclusion criteria included FTMH >400 μm, presence of ERM, and aphakia in the study eye.

The researchers concluded that the OASIS trial demonstrates the long-term efficacy and safety of ocriplasmin, providing improved resolution of symptomatic VMA compared with previous phase 3 trials, with no additional safety signals identified.

pSivida to Study Cancer Drug for Wet AMD

Delivery in sustained-release format

■ pSivida Corp. (Watertown, MA), a developer of sustained-release drug delivery products primarily for eye diseases, is preparing to begin an early-stage clinical trial using an approved cancer drug to combat wet AMD. The decision is based on data from two animal studies of an injectable, sustained-release insert utilizing pSivida’s proven Durasert implant to deliver a tyrosine kinase inhibitor (TKI) at therapeutic levels.

The preclinical data demonstrated that, at the completion of the studies in well-established animal models, the TKI insert was comparably efficacious to an injection of an FDA-approved AMD biologic both in preventing choroidal neovascularization and reducing vascular leakage. On the basis of these results, pSivida plans to advance toward clinical trials of the Durasert TKI insert for wet AMD, including toxicology studies necessary for an investigational new drug application. The company did not name the specific cancer drug being used in the trial.

Paul Ashton, PhD, former president and CEO of pSivida said, “The most commonly used therapies for the disease target only VEGF and require injections as frequently as monthly. However, blocking VEGF alone does not result in long-term suppression of the disease, and studies suggest that platelet-derived growth factor (PDGF) as well as VEGF may play an important role in AMD. The TKI used in our insert is known to block both VEGF and PDGF. Our goal is to effectively treat AMD on a sustained basis for six months with a single injection, targeting both VEGF and PDGF while avoiding the toxic systemic side effects of TKIs and the frequent injections of current AMD anti-VEGF biologics.”

In cancer therapy, TKIs are taken orally, but their significant toxicity prevents their systemic use to treat AMD. By using Durasert sustained-delivery technology, pSivida plans to deliver a TKI dose directly to the retina that is approximately 1,000 times less drug than is used in a course of cancer therapy.

In other pSivida news, industry veteran Dario Paggiarino has been named vice president and chief medical officer. He previously held positions with LPath, Alcon, and Pfizer Global. RP