Specialty pharmaceutical company Actavis and Allergan last month entered into a definitive agreement under which Actavis will acquire Allergan. The transaction is valued at approximately $66 billion, and will create one of the top 10 global pharmaceutical companies by sales revenue, with combined annual pro forma revenues of more than $23 billion anticipated in 2015. The transaction has been unanimously approved by the Boards of Directors of Actavis and Allergan, and is supported by the management teams of both companies. Allergan had for months been the target of a takeover attempt by Valeant Pharmaceuticals.

“We will establish an unrivaled foundation for long-term growth, anchored by leading, world-class blockbuster franchises and a premier late-stage pipeline that will accelerate our commitment to build an exceptional, sustainable portfolio,” said Brent Saunders, CEO and president of Actavis. “The combined company will have a strong balance sheet, growing product portfolios and broad commercial reach extending across 100 international markets. Our combined experienced management team is dedicated to driving strong organic growth while capturing synergies and maintaining a robust investment in strategically focused R&D.” Based in Dublin, Ireland, Actavis has U.S. headquarters in Parsippany, N.J.

David Pyott, chairman and CEO of Allergan, added, “Today’s transaction provides Allergan stockholders with substantial and immediate value, as well as the opportunity to participate in the significant upside potential of the combined company. We are combining with a partner that is ideally suited to realize the full potential inherent in our franchise. Together with Actavis, we are poised to extend the Allergan growth story as part of a larger organization with a broad and balanced portfolio, a meaningful commitment to research and development, a strong pipeline and an unwavering focus on exceeding the expectations of patients and the medical specialists who treat them. I am thankful for the hard work and dedication of our employees, and I’m confident they will make many valuable contributions to the combined company. Looking to the immediate future, all of us at Allergan are excited to roll up our sleeves and work closely with the Actavis team to ensure a smooth transition.”  

The combined company will be led by Mr. Saunders. The integration of the two companies will be led by the senior management teams of both companies, with integration planning to begin immediately in order to transition rapidly to a single company. The combined company will provide a strong commitment to R&D, with an annual investment of approximately $1.7 billion, focused on the strategic development of innovative and durable value-enhancing products within brands, generics, biologics and OTC portfolios. The combination is expected to add approximately 15 projects in near- and mid-term development to Actavis’ robust development portfolio.  

The transaction is subject to the approval of the shareholders of both companies, as well as customary antitrust clearance in the United States, the European Union and certain other jurisdictions, and is anticipated to close in the second quarter of 2015.

AMD Risk Score From OCT Data
Stanford University scientists have
found a new way to forecast which patients with age-related macular degeneration are likely to suffer from the most debilitating form of the disease. The new method predicts, on a personalized basis, which patients’ AMD would, if untreated, probably make them blind, and roughly when this would occur. Simply by crunching imaging data that is already commonly collected in eye doctors’ offices, ophthalmologists could make smarter decisions about when to schedule an individual patient’s next office visit in order to optimize the chances of detecting AMD progression before it causes blindness.

Until now, there has been no effective way to tell which individuals with AMD are likely to progress from the dry to the wet stage. Current injection treatments are costly and invasive, precluding the notion of treating people with early or intermediate stages of AMD. Doctors and patients have to hope the next office visit will be early enough to catch wet AMD at its onset, before it takes too great a toll. In a study published in the November issue of Investigative Ophthalmology & Visual Science, the researchers derived a formula that they say predicts, with high accuracy, whether a patient with mild or intermediate AMD will progress to the wet stage. The formula distinguishes likely from unlikely progressors by analyzing patient data that’s routinely collected by spectral domain optical coherence tomography.

The November 2014 article “ In the Dry-Eye Pipeline: Slow Progress” incorrectly indicated that lifitegrast manufacturer Shire had submitted clinical trial data to the Food and Drug Adminstration, and that the data was under review. In fact, Shire intends to submit a New Drug Application for lifitegrast as a treatment for the signs and symptoms of dry-eye disease in adults in the first quarter of 2015.

Review regrets the error.
“Right now, a patient who goes into the ophthalmologist’s office typically gets an SD-OCT scan anyway,” said the study’s senior author, Daniel Rubin, MD, assistant professor of radiology and of biomedical informatics. “Our technique involves no new procedures in the doctor’s office—patients get the same care they’ve been getting anyway. We’ve simply added on a computerized image-processing step that analyzes not only that scan but any previous ones available from that same patient’s earlier visits.”

From this computerized analysis, the investigators are able to generate a risk score: a number that predicts a patient’s likelihood of progressing to the wet stage within one year, three years or five years. The likelihood of progression within one year is most relevant, because it translates into a concrete recommendation: how soon to schedule the patient’s next office visit.

Until now, attempts to predict AMD progression have relied on eye doctors examining color photographs of the retina taken in their offices. There is no way to translate that information into risk scores. The high-resolution imaging technique, Dr. Rubin said, provides much richer detail. “You can almost see individual cells,” he said. Plus, it is far more amenable to digital analysis. Previously proposed predictive models have shown some accuracy over long periods of time, but none has been adequately accurate over the shorter, one-year time frame that’s relevant to making decisions about office-visit frequency, Dr. Rubin said.

The Stanford team analyzed data from 2,146 scans of 330 eyes in 244 patients seen at Stanford Health Care over a five-year period. They found that certain key features in the images, such as the area and height of drusen, the amount of reflectivity at the macular surface and the degree of change in these features over time, could be weighted to generate a patient’s risk score. Patients were followed for as long as four years, and predictions of the model were compared with actual instances of progression to wet AMD. The model accurately predicted every occurrence of progression to the wet stage within a year. About 40 percent of the time when the model did predict progression to wet AMD within a year, the prediction was not borne out.

“No test gets it right 100 percent of the time,” Dr. Rubin said. “You can tweak the model to trade off the risk of telling someone they will progress when they actually won’t against the risk of telling them they won’t progress when they actually will. With AMD you really don’t want any false negatives, so you tune the model accordingly. The downside is that some patients will wind up being told to come in sooner than, in fact, they probably need to. But that’s nothing compared with the downside of a patient at high risk for progression’s not coming in soon enough.” Dr. Rubin emphasized that this proof-of-principle study needs to be followed up by a larger study, ideally using data gathered from patients seen at other institutions. He and his associates have begun such a study.

Medicare Billing Status Passed for Omeros’ Omidria
Omidria (phenylephrine and ketorolac
injection, Omeros) 1%/0.3%, approved earlier this year by the Food and Drug Administration for use during cataract surgery or intraocular lens replacement, has received transitional pass-through status from the Center for Medicare & Medicaid Services.

Transitional pass-through status will allow ambulatory surgery centers and other outpatient facilities to bill Medicare and other insurance providers for Omidria using a temporary Healthcare Common Procedure Coding System code unique to Omidria. Pass-through status allows for separate payment for new drugs and other medical technologies that meet specific clinical-value and cost requirements. Pass-through status for Omidria will become effective on January 1, 2015, and will remain in effect for two or three years, after which CMS and other insurance providers will make a new reimbursement determination. Reimbursement will be based on the product’s wholesale acquisition cost of $400 to $500 per single-use vial.

“The recent approval of pass-through reimbursement for Omidria means that surgeons, surgicenters, and patients will have no additional costs associated with the use of Omidria,” says Eric Donnenfeld, MD, of Ophthalmic Consultants of Long Island. “There will be direct reimbursement to the surgicenter by Medicare. This is a win/win for surgeons and patients. We will be able to use an FDA-approved product during cataract surgery that improves surgical outcomes and the patient experience with the cost of the medication being paid directly by Medicare.”

Omidria is the only FDA-approved product for intraocular administration that prevents intraoperative miosis and reduces postop pain. In a recently published study, it was found to maintain mydriasis, prevent miosis and reduce early postop pain when administered in irrigation solution during intraocular lens replacement, with a safety profile similar to that of placebo.

According to Dr. Donnenfeld, Omidria fills a significant unmet need in ophthalmology. “This is the first FDA-approved product designed to prevent pupillary miosis and reduce postoperative ocular pain to create a more tolerable patient experience,” he says. “The combination of intracameral phenylephrine and ketorolac will not only improve surgical results, but will also improve both the patient and surgeon experience in the operating room. Predicting who will develop pupillary constriction is difficult, if not impossible, and once the pupillary constriction begins, the surgeon has to change his technique and sometimes stop in the middle of the procedure. Pupillary constriction may convert a conventional cataract surgery into a complex case that requires urgent and specialized treatment that wasn’t previously expected. In addition, successful surgeons pay attention to the patient experience. Omidria is an important step in moving surgeons from conventional to refractive cataract surgery.”

The company plans to launch Omidria no later than early 2015.  REVIEW