Article | March 1, 2024

State Of The Orphan Space

Source: Life Science Leader
wayne koberstein

By Wayne Koberstein, Executive Editor, Life Science Leader
Follow Me On Twitter @WayneKoberstein

D. Treco Headshot - Cropped
Douglas Treco

Inozyme’s Leader Shares Informed Views

In the decades since the United States passed the Orphan Drug Act in 1983, its policies have succeeded in raising the number of drugs developed for rare diseases. Incentives in the Act were so effective, in fact, orphan drugs may have replaced blockbusters as the driving force of biopharma. The only hitch: replacing the revenue from blockbusters seems to require that the orphans carry unprecedented and perhaps limitless prices.

“The original idea behind the Orphan Drug Act was to induce more companies to work on drugs for rare diseases, because normally a company would not have made enough money doing that,” says Douglas A. Treco, Ph.D., Inozyme CEO and chairman of the board. “But now that’s been flipped on its head and people say, ‘How do we really optimize our ability to make money in this business? We’ll find a rare disease.’”

Our recent conversation with Treco sheds light on the current environment for developing new drugs in the rare disease space. Inozyme is developing a new drug, INZ-701, for treating three rare conditions: ENPP1 Deficiency, ABCC6 Deficiency and calciphylaxis, which interrupt normal mineralization. Treco’s perspective includes his experiences as a leader of multiple companies and an active observer of the biopharma industry. He judges the outlook for the orphan-drug space, particularly the issues of company financing, IPOs, FDA trials and their fluctuating costs, technological innovations in the field, and others related to rare disease drug development. Adding the real-life perspective of his growing company, he cites relevant details of Inozyme’s history, its progress in research, and approach to clinical development, and he offers his own business and management insights on the orphan space.

Despite Treco’s critical appraisal of companies that push profitability at the top of their orphan drug priorities, he expresses confidence in the system that underlies innovation in this space. “There is still a huge interest in developing orphan drugs, and investors are still very eager to put money behind that. It has been very lucrative for investors for a long time, and good companies that have good products will continue to be able to get funding, and that’s just the way it should be.”

Products Over Platform

Treco points out that orphan drugs attract development for more reasons than profits. Rare diseases tend to have mechanisms that present narrow targets compared to mass-scale conditions such as heart disease or diabetes.

“One of the reasons why orphan drugs and rare diseases are attractive is because in most cases they have a defined genetic component,” he says. “In most cases, you can look at something that’s missing, such as an enzyme, and if you can replace it or find a way to accomplish the same thing, you can treat the disease. Most major diseases are multifactorial. In Type 2 diabetes and probably Alzheimer’s disease, there are so many factors involved that you need massive studies to tease out very small effects.”

Treco led companies that developed second-generation products to treat some diseases for the first time, such as erythropoietin for anemia, Vpriv for Gaucher Disease, Zilbrysq for myasthenia gravis, and Replagal (agalsidase alfa) for Fabry disease. “With Fabry, we were at the forefront and there was no competition; we were very close to the beginning. Here, at Inozyme, the product we’re working on now is one of only a couple I’ve led with a wide-open noncompetitive position. It’s a nice position to be in, but I still don’t want to charge prices that are inaccessible.”

He considers Inozyme a unique company, founded on licensing a molecule and a therapeutic approach out of a group at Yale in 2017. “As companies hit roadblocks that force them to pivot strategically, they will sometimes change their path completely, perhaps to a new molecule that has better properties or better safety, or to a supplier model, delivering services from their technology platforms. But in the original design and concept of our molecule, and the diseases we want to treat, we haven’t changed our approach at all since the beginning, and that’s why I say our company is unusual.”

Treco suspects some companies pivoting to new molecules wind up in the orphan space, hoping for large financial windfalls. “Platform companies look at their pipelines and decide they should be finding other rare disease drugs that are completely outside of their area. They are being opportunistic in that regard and really hungry for any rare disease drug. It is kind of where we’re at now. New drugs for rare diseases do hold a lot of promise for people, but I don’t think they deserve to have whatever price you want to charge for them out there in the market. The good news for patients is that insurers see the burden that these patients experience and see how new drugs can reduce overall lifetime treatment costs, so they are generally tolerant of high prices for rare disease drugs. Ultimately, though, there will be a breaking point given the large number of rare diseases and patients out there.”

What is his solution? Competition. “What I’ve tried to bring into the industry are competitive products for rare diseases so that patients have choices, and that those choices will lead to better prices for people because there’s an alternative. It will become more prevalent in some rare diseases as technology changes and new approaches come up, and there will be more competitive products to help keep these prices down.” And sometimes, the discovery of a rare disease drug produces new knowledge that spills over into the treatment of more complex diseases — depending on whether, perhaps, the developer company genuinely chases the science, not just the black ink.

Keep On Keeping On

Inozyme has traveled the road of clinical development all the way to Phase 3 at this point, with several Phase 2 and earlier trials of its drug in other indications. As a well-experienced traveler on that path, Treco has encouraging but realistic words of advice for others who will make the same trek.

“In this industry, I would tell people to not get discouraged,” he says. “There’s a lot ahead for you, and you’re going to hit roadblocks as early as preclinical testing where you will have to deal with issues. You’re going to get questions from regulators, and they get more and more challenging as you go along. You just can’t give up. We’re lucky at Inozyme to be working on an enzyme replacement therapy. When people are missing an enzyme and you give them that enzyme back, the enzyme typically functions outside the cell, so, the success rate there is extraordinarily high, on the order of 80 percent. With a lot of other more complicated metabolic diseases, there’s no determining genetic component. So, don’t get discouraged. Perseverance is key here.”

Perseverance — and confidence based on diligent development. “There are two ways to build value in this industry. One is to get your drug approved and sell it, the other is for pharma companies to take notice and see the value you have created. That gets translated into shareholder interest, share-price increase, and being able to raise money, or sometimes even acquisitions. There are still a lot of pharmas that have a big interest in rare diseases.”