Answering The Call To Develop Novel Drugs For Rare Diseases

By Gabi Hanna, MD

Faced with a serious diagnosis or an unexpected hospitalization, patients and their families are often left feeling like they’ve been hit with a gut punch. This insecurity is compounded when the diagnosis is some type of rare condition, such as an uncommon sarcoma or an ailment that lacks widely accessible treatment like acute pancreatitis.

For those in the field of drug development, the desire to expedite the delivery and implementation of new treatments is tempered by an important but lengthy process created to ensure the efficacy and safety of any new protocol. These obstacles can feel like Sisyphean task when you acknowledge the decade-plus timeline and multi-billion dollar costs typically associated with bringing a new drug to market. That’s before we acknowledge the reality that 90 percent of drugs that enter clinical trials fail. 

Approximately 95 percent of all identified rare diseases currently have no approved treatment options. Developing drugs for rare diseases is a complex process with unique challenges and opportunities.

Despite these monumental hurdles, working in the field of drug development remains captivating because opportunity still abounds for major advancements that will improve the lives of millions of people the world over.

Standing out in the crowd requires four important components: entrepreneurial thinking, accelerating innovation, financial considerations, and a commitment to science.

Entrepreneurial Thinking

Innovation is at the heart of nearly every successful endeavor of the last century. Whether it was Henry Ford, Steve Jobs, Jeff Bezos, or Elon Musk, entrepreneurs committed to taking risks in the pursuit of new approaches have transformed the world. Across decades and industries, that spirit has been proven to mean more than using the latest technology, for instance. It’s also come to demonstrate that efficiency, speed, and an ethic for doing more with less will outperform gargantuan budgets time and again.

For many in biotech, however, operating with an entrepreneurial mindset is the antithesis of their modus operandi. As a sector, biotech has long been dominated by behemoth pharmaceutical companies clinging to status quo operations that slow research and stifle discovery. Often, these blue-chip companies prioritize short-term, shareholder-driven quarterly profits over long-term patient outcomes, leaving critical advancements stalled in the lab.

The stagnation of Big Pharma presents a tantalizing opportunity for those willing to bet on themselves. Startups and smaller firms that harness entrepreneurial practices that prioritize efficiency, outside the box thinking, and passion for healing over rigid financial metrics can indeed break through the noise.

This doesn’t mean being cavalier. Instead, it means embracing a balanced approach: managing risk effectively while accelerating data analysis, ensuring patient safety, and maximizing long-term benefits. At Lamassu, our team has worked hand-in-glove with the FDA and major institutions to find ways we can accelerate the drug development process, whether through parallel development or alternative treatment protocols, to more quickly increase drug dosages and a reliance on smaller data sets.

Accelerating Innovation

The scientific and logistical hurdles in rare disease drug development are significant. Small patient populations make it difficult to recruit enough patients for traditional large-scale clinical trials. This often leads to the use of innovative trial designs, such as adaptive or basket trials, and reliance on smaller data sets.

Further, a lack of expertise and infrastructure can make it challenging to conduct research and deliver care. The high degree of scientific uncertainty and the small patient numbers can lead to a higher risk of failure, as there may not be enough data to show statistical significance or confirm efficacy.

When it comes to data, accelerating innovation means we must look beyond large-scale randomized controlled trials, which are often not possible with rare diseases. Instead, here we have an opportunity to prioritize other data points, including real-world evidence, patient registries, and biomarkers.

Smaller patient pools, combined with a clear understanding of the disease, can mean faster clinical trials and approval timelines. Additionally, regulators can and must be more willing to consider a drug's effectiveness in the context of the high unmet need rather than strictly adhering to traditional standards of absolute cure. This means a therapy that provides a significant benefit, even if not a cure, may be approved.

Fortunately, regulatory bodies like the FDA are increasingly adopting flexible and innovative approaches to accelerate the development and approval of drugs for ultra-rare diseases (e.g., those affecting fewer than 1,000 people). These programs may allow for three key variables: the acceptance of nontraditional data, shorter developmental paths, and consideration of unmet need.

Financial Considerations

While innovation can help propel us forward, the business of America’s biotech sector is at a precipice. The industry faces serious obstacles, including funding challenges, regulatory uncertainty, outmoded intellectual property laws, and investor wariness, which have combined to create a fragile environment. Following the global pandemic, the market has seen a significant decline in initial public offering (IPO) activity, down dramatically from its 2020 and 2021 levels, and venture capital, once a pillar of any startup’s business plan, has tightened. Beyond Wall Street, American companies are seeing serious competition from foreign investors backed by China, Saudia Arabia, and other nations.

Here again we find both challenges and opportunities. First, the market for rare disease drugs, often called orphan drugs, is small. The return on investment (ROI) for rare disease drug development can be low, especially compared to drugs for larger markets. This makes them less attractive to large pharmaceutical companies focused on blockbuster drugs for common conditions. Due to the limited patient pool, the high cost of research and development (R&D), and clinical trials, costs often aren’t recouped through high sales volume.

While there's growing political pressure and regulatory scrutiny on drug pricing, which could diminish this economic model and discourage future investment, there is a strong business case for this important work. Governments have historically tried to incentivize this research through programs like the Orphan Drug Act, Rare Pediatric Disease Priority Review (RPDD), and Priority Review Vouchers (PRV) in the U.S. and other countries. These initiatives offer benefits such as tax credits for clinical research, making the work both possible and potentially profitable.

Strategic thinking, foresight, and planning, which are hallmarks of successful entrepreneurs, present an opportunity for those willing to tackle the challenges of rare diseases. By demonstrating the success of our innovative processes in the lab, Lamassu Biotech has been able to secure major partnerships with leading institutions like Mayo Clinic and Cleveland Clinic, as well as international engagements with distinguished companies like Adamed. These partnerships have helped strengthen investor confidence in our process.

Commitment To Science

Business acumen and strategic thinking, while important, can only take you so far. What must be resolute is a commitment to science. What allows for the swiftest development of new novel therapies is not big money but quality science garnered through rigorous preclinical study. Scientific transparency is critical for regulatory support, coalition building, and, most importantly, providing patients with peace of mind that they can trust new treatment options. This is particularly critical following the COVID-19 pandemic and persistent questions about the efficacy of treatments and validity of information provided to the public.

Ultimately, while financial and regulatory factors are critical, the core mission of the biotech and healthcare industries is to improve human health. The high personal costs to patients and families living with rare diseases creates a moral imperative to pursue solutions more expeditiously.

For drug development scientists, the motivation must remain to tackle the toughest medical problems and make the biggest impact.

About The Author

Gabi Hanna, MD, is the CEO and cofounder of Lamassu Biotech, a private clinical-stage biopharmaceutical company that uses innovative processes to speed up the development of transformational treatments.