Eyeing the effects of ocriplasmin

Drug helps carefully selected patients, surgeons report as they continue to work on the why.

By Vanessa Caceres, Contributing Editor

The tale of ocriplasmn is likely best described as “still under construction.”

Approved in 2012, ocriplasmin (Jetrea, ThromboGenics) debuted on the market with some experts concerned about its safety and side effects. However, retinal surgeons familiar with the drug say that in carefully selected patients, ocriplasmin effectively treats vitreomacular adhesion with minimal and only transient side effects — and it can help with avoiding surgery.

COURTESY RISHI SINGH, MD

Gaining support

“The idea behind ocriplasmin has been talked-about and dreamed about for a long time,” says Pravin U. Dugel, MD, managing partner, Retinal Consultants of Arizona and Retinal Research Institute LLS, Phoenix, and clinical professor, USC Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles. “Like any first-of-its-kind drug, there are lots of lessons we have to learn. We saw that happen with Lucentis [ranibizumab, Genentech] as well.”

“I’ve been more comfortable with it over the past year as we’ve learned more about the types of patients it works well with,” says Carl D. Regillo, MD, FACS, director, Retina Service, Wills Eye Hospital, and professor of ophthalmology, Thomas Jefferson University, Philadelphia.

Rishi Singh, MD, assistant professor of ophthalmology, Case Western Reserve University, Cleveland, notes the drug’s significant advantages. “With ocriplasmin, there’s no need for anesthesia or time away from work or the need for family members to help patients,” he says. “It’s been a nice thing to have in our armamentarium, albeit not a perfect one.”

In practice

So how do retinal specialists most familiar with ocriplasmin injections make it work effectively in their patients? Here are some lessons learned.

1. Careful patient selection is crucial. Research and clinical experience show that patients who are phakic, under age 65, have a vitreoretinal macular adhesion of 1500 microns or less, and who do not have an epiretinal membrane are most likely to have success with ocriplasmin, Dr. Singh says. In a study led by Dr. Singh and published last year in the British Journal of Ophthalmology, the overall response rate to the drug in the 17 patients studied was 47.1% per results viewed via spectral domain optical coherence tomography.¹ However, those who met three of the four positive predictive criteria had a 50% success rate. In patients with all four criteria, the success rate improved to 75%.

Another study, co-authored by Dr. Regillo and published in the May 2015 issue of the American Journal of Ophthalmology, reported a 50% success rate.² If patients do not meet the ideal criteria for success with ocriplasmin, it’s probably best to go right to surgery, Dr. Regillo says. “Yet doing [ocriplasmin] first is a very good option in patients with ideal features.”

“We can confidently tell our patients there’s an approximately 50% chance they’ll avoid surgery,” Dr. Dugel says. “And if they do need surgery and ocriplasmin fails, it won’t have a negative impact on the surgical outcome.”

Dr. Regillo points out that another advantage with ocriplasmin in a phakic patient is that if the injection works, then two surgeries are effectively avoided — vitrectomy and cataract surgery.

2. Take chair time with the patient to explain how the medication works. “It’s a big counseling discussion,” Dr. Regillo says. “There are two very different interventions, one with the OR with surgery, and the other with an office-based injection. With the patient, what they may or may not experience is very different. It’s a time-consuming dialogue.”

Dr. Dugel likes to explain that safety with ocriplasmin is good but that in a minority of patients, changes occur that are not yet fully explained (see No. 4, below). He also points out that most changes — if they do occur — are transient and that patients recover fully. After a thorough discussion about ocriplasmin’s efficacy and safety profile, what is known and unknown, he gives qualified patients the choice of surgery or ocriplasmin injection; the majority want to try the injection before surgery.

3. Think of ocriplasmin like surgery. This is important because patients might think they’ll get the injection and get better right away with no side effects, Dr. Regillo says. Then, something else happens. “When it works, it anatomically fixes the problem quickly but functionally, it’s typically a slow recovery. It’s somewhat of a disconnect because it’s more similar to surgery.” This is another area where a frank, thorough conversation with the patient can keep expectations in check.

Yet another reason that surgeons should bear the surgery comparison in mind is when they think about side effects, Dr. Dugel says. For example, if a patient has surgery for vitreomacular adhesion, the surgeon likely will not ask about next-day flashes, floaters or changes in color because he or she feels confident those will go away quickly if they occur at all. The same concept applies with ocriplasmin, he says. “We need to ask how this compares to surgery and what is reversible versus not reversible. We need to keep everything in proper perspective.”

4. Transient side effects exist. A report published in the June 2015 issue of Retina analyzed premarketing and postmarketing experiences with ocriplasmin and categorized adverse events into eight categories: acute reduction in visual acuity caused by worsening of macular pathology or development of subretinal fluid; electroretinogram changes; dyschromatopsia; retinal tears and detachments; lens subluxation or phacodonesis; impaired pupillary reflex; and retinal vessel findings.³ There were also ellipsoid zone findings. “Adverse events were generally transient, and characteristics of these adverse events were generally similar between the premarketing and postmarketing experience,” according to the study.

In Dr. Singh’s study, seven of the 17 patients studied experienced transient outer segment ellipsoid zone loss.¹ There was also subretinal fluid presence after injection in five patients.

COURTESY RISHI SINGH, MD

On a practical level, the side effects were not strong or chronic enough to prevent certain surgeons from using ocriplasmin. “When the drug works, [then] the side effects are transient, common and mainly related to what the drug is intended to do. So, there’s release of the vitreous gel and you get flashes and floaters,” Dr. Regillo says. He also has seen patients experience decreased vision or discoloration that can last a few weeks or longer. He has not seen side effects in non-responders.

Although most patients do not have safety issues, when they do occur, it’s not yet always clear why, Dr. Dugel says. Still, he thinks it important to keep side effects in perspective. “Let’s ask how many patients have their vision permanently affected. It’s very, very few. However, it’s important to keep trying to understand these patients.”

5. The drug’s playbook is still a work in progress. There’s plenty more that retinal surgeons would like to know about ocriplasmin. One clinical trial that many are eagerly awaiting the results from is OASIS, short for Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole. The OASIS study collected data from various sites and tracked patients for two years. A press release in March from ThromboGenics said in OASIS, about 42% of patients treated with ocriplasmin had their adhesion resolved by day 28 compared with 6.2% of patients receiving a sham injection.⁴ The drug’s safety profile was consistent with its already reported safety profile as known from the approved label, according to the press release. Further results from OASIS will be reported at larger clinical meetings later this year.

Dr. Singh believes the Holy Grail will involve studies showing if vitreous separation with ocriplasmin can occur in diabetic patients. He’d also like to see more research related to small macular holes, which he says is an approved use for ocriplasmin in other countries. Dr. Dugel adds that the unknowns about ocriplasmin’s safety profile — and why certain side effects occur in some patients and not others — will continue to be reviewed.

Dawn of a new drug class?

Dr. Dugel thinks ocriplasmin has opened the door for more drugs to treat vitreomacular adhesion — instead of just observing the patient or moving straight ahead to surgery. “We know this is just the beginning of drugs in its class. I think it will open the door for many other drugs in the same category.” OM

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