Advancements in Biotherapeutics for Retinal Disease and What It Means for the Future of Gene Therapy

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A treatment for retinal dystrophies may become the first gene therapy drug approved by the FDA. It if succeeds, others are sure to follow but what issues do biotherapeutics firms face?
Image source: Flickr CC user Gordon Wrigley

Are we finally about to see a change in the U.S. gene therapy sector? Stark Therapeutics would certainly like us to think so. The company recently announced that one of its drugs has succeeded in late-stage clinical trials. The medicine in question treats patients with rare, inherited retinal dystrophies that eventually lead to complete blindness. Not only were patients who received the therapy better able to maneuver in dimmer light than before, they did so at a statistically higher percentage than the control group, which had received no treatment.1

While there are many gene therapies currently undergoing clinical trials—at least 320, as of 20122—none have ever received FDA approval. In fact, only one type of gene therapy has garnered approval in a regulated market worldwide. Glybera, which treats a rare disorder that can cause severe pancreatitis, received the green light from the European Commission in 2012.3 But despite having achieved this major accomplishment, the drug has yet to launch, fueling skepticism about the efficacy of gene therapies.

When gene therapy first came into clinical development over two decades ago, many people considered it a source of hope in treating rare genetic disorders. Unfortunately, in the years since, it has failed to deliver on that promise. But if Stark’s retinal disease drug does win FDA approval, the crossing of this major hurdle will likely encourage other biotherapeutics companies to follow suit. That said, to do so successfully will require firms to ensure that all safety and quality standards be followed at every step of the way.

Potential Hurdles Faced by Gene Therapy on the Road to Final FDA Approval

Public skepticism regarding the efficacy and safety of gene therapy stems from a few sources. Gene therapies typically make use of a viral vector to deliver the corrected gene into target cells. But what if the vector ends up targeting the wrong cell? The effects of incorporating genetic material into perfectly functional DNA could have drastic repercussions. Some gene therapy drugs have even caused spontaneous mutations or even tumors. In terms of the delivery vehicle, what if the viral vector regains its original function? What will happen to the affected patient then? And like other biotherapeutics, what if the gene therapy triggers an immune response? The ultimate goal of gene therapy is to cure disorders in patients, not cause more problems for them.

The embodiment of these fears became reality when a patient died during clinical trials in 1999. The death occurred as the result of a massive immunogenic reaction to the adenoviral vector. Subsequent investigation revealed that the death could have been prevented and was the result of major lapses in safety and compliance. The latter, more than anything else, damaged public perception of gene therapy as a safe course of treatment.

In the case of Stark’s retinal drug, they may face difficulties aside from those normally experienced by gene therapies. While they claim their tests showed that the effects of the drug were permanent, other firms that replicated the study say the benefits wore off after a year or two. The disparity between the two findings serves as a point of contention and one that, no doubt, will receive FDA scrutiny. Since gene therapy modifies and corrects faulty genetic material, it is assumed to be a permanent cure. If the results are temporary, then is it actually an effective treatment?

Ensuring Biotherapeutic Quality Can Aid Companies’ Efforts to Gain FDA Approval

The discrepancies between Stark’s results and those of other companies will likely need to be reconciled before the drug can obtain final approval. At the very least, they must demonstrate that the effects observed in clinical trials can be reproduced. Considering the concerns about how long the positive results last, longitudinal studies may even be required.

No matter how the company decides to address these issues, FDA guidelines for gene therapy drugs are still in nascent form. While Stark’s issues may have nothing to do with procedural or material quality, other firms should begin with these points to build a solid foundation in their research efforts. To gain FDA approval, biotherapeutics firms hoping to launch a product will likely have to prove the following:

  • Safety and efficacy: Are there minimal adverse side effects in the majority of the patients? Does it target the correct cells? Does the drug actually correct the disorder?
  • Length of efficacy: How long do the benefits last? Permanently? Ten years? One year? Obviously, shorter periods of time are not as ideal.
  • Good manufacturing procedures: How is the drug manufactured? Are its raw materials of good quality? For example, do the viruses used as vectors remain safe delivery vehicles that do not recover their original properties?

Considering gene therapy’s murky history, any drug that has a chance of reaching market will face intense scrutiny from the FDA. Biotherapeutics firms will need to demonstrate that their results come from procedures emphasizing safety and quality. The 1999 clinical trial death, for example, was the result of failing to exclude the patient from the study. He did not fit the profile for participants and that difference should have been flagged. Along those lines, documentation provided to the FDA must provide evidence that any deviations are within acceptable limits, and not ones that will have massive repercussions. After all, gaining approval is only the first step. Biotherapeutics firms also want to make sure that quality and safety continues down the line, in order to prevent product recalls 1-2 years after launch.

Despite the positive results of Stark Therapeutics’ clinical trials, they have yet to garner FDA approval. It may be that another gene therapy drug becomes the first to overcome this hurdle in the U.S. market. Regardless of any issues and their corresponding causes that may arise, biotherapeutics companies developing gene therapy drugs must emphasize quality and safety at every stage of the discovery, development and manufacturing process. Investing in such a strategy is the only way to sway public perception and lift the shadow lingering over the gene therapy market.

The BIOVIA Total Quality Solution is a complete suite of tools that supports your company’s efforts at executing a total quality and safety strategy. Among its benefits are consistent enterprise-wide document management of all quality and compliance procedures, better process understanding, and enhanced knowledge sharing. Supported by these tools, firms can develop gene therapies with confidence, knowing that they are backed by a system capable of maintaining records according to regulatory guidelines and reducing compliance risks. In addition, any deviations from acceptable limits can be flagged by the system, allowing the organization to determine necessary improvements earlier in the process and avoid unwanted repercussions later down the road. Contact us today to learn more.

  1. “Eye Treatment Closes In on Being First Gene Therapy Approved in the U.S.,” October 5, 2015,
  2. “The State of Gene Therapies: The FDA Perspective,” May 2012,
  3. “Glymera Gains Official EMA Nod as First Gene Therapy,” November 2, 2012,

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