FDA Advisory Committee Backs Alnylam's RNAi Therapy Patisiran for ATTR Cardiomyopathy Expansion: Is the Rare Disease Drug an Overlooked Billion-Dollar Molecule?

Yesterday, the FDA committee voted in favorAlnylam's RNAi Therapy PatisiranIndicated for the treatment of transthyretin-mediated (ATTR) amyloidotic cardiomyopathy. As the first successfully marketed siRNA drug, patisiran was previously approved for the treatment of a rare disease—hereditary ATTR (hATTR) amyloidosis with polyneuropathy in adults—which affects approximately 50,000 patients worldwide. If this indication expansion is approved, its patient coverage will also include wild-type ATTR (wtATTR) amyloidosis, which affects approximately 200,000–300,000 people globally.

Alnylam has rapidly emerged as the leader in small nucleic acid therapeutics through the development and successful commercialization of drugs for rare diseases. The company is expanding indications for its approved therapies to further grow its market size, while leveraging the technological expertise and insights gained from rare disease drug development to tackle common conditions such as hepatitis B and non-alcoholic steatohepatitis (NASH).

This represents one of the significant values of innovative pharmaceutical companies specializing in rare diseases. In China, these enterprises must strike a balance between drug innovation and accessibility, sustain sales growth following price negotiations, and continue investing in research and development while effectively managing cash flow and controlling costs. Most critically, unlike other disease categories, rare diseases constitute a “broad concept” encompassing a multitude of conditions. Merely establishing reasonable project initiatives and identifying patients presents considerable challenges. Furthermore, subsequent commercialization and medication access assurance are complex due to their strong association with social responsibility.

An innovative rare-disease pharmaceutical company stated that it has always maintained an open attitude toward fundraising, but finding investors willing to collaborate is not easy.

In fact, the commercialization prospects for innovative pharmaceutical companies focused on rare diseases can be highly attractive. For instance, Vertex’s growth from a biotech firm to a biopharma company was driven in part by its steadfast commitment to its cystic fibrosis (CF) program. In the first half of this year, CF drugs generated $4.337 billion in revenue for the company, with these substantial earnings continuously fueling the development of other innovative therapies.

Rare-disease pharmaceutical companies walking a tightrope can become valuable “catfish” in the biopharmaceutical sector, whether through technology or business models, and can also yield “billion-dollar molecules.”

Rare diseases, by virtue of their “rarity,” have revealed a blue-ocean opportunity for some biotech companies: large pharmaceutical firms do not prioritize investment in this area, competition is less intense than for common diseases, and supportive policies—such as accelerated approval of clinical trials and extended exclusivity periods for rare-disease drugs—are in place. Meanwhile, many rare-disease therapies command high prices, yet require relatively low sales and marketing expenditures due to the inelastic demand from patients, enabling biotech firms to maintain end-to-end control from R&D through commercialization.

Innovative companies can quickly stand out. For example,Rare Disease Gene Therapy Company Krystal Biotech,VYJUVEK™, a product indicated for the treatment of dystrophic epidermolysis bullosa (DEB) in patients aged 6 months and older, received FDA approval in May this year. It is an FDA-approved topical gene therapy and the first reusable gene therapy, enabled by its independently developed STAR-D technology platform, which facilitates efficient, repeated delivery of therapeutic genes to skin cells.

Krystal Biotech’s successful operations have also made the company popular in the market, with its stock price rising from $10 at the time of its initial public offering to $124 today.

There are approximately 9,000 patients with dystrophic epidermolysis bullosa (DEB) worldwide.However, a noteworthy aspect in the field of rare diseases is that the patient population may be larger than anticipated and shows an upward trend, largely due to historically low screening and consultation rates in the absence of specific therapies.In addition, for many rare diseases caused by genetic mutations, the availability of targeted pharmacotherapies has significantly extended patient survival, prolonged treatment durations, and resulted in annual incident cases outnumbering deaths.

AsGenentechAs the first biotech company to master recombinant protein technology, it highly valued its growth hormone for treating rare diseases such as dwarfism. With continuous improvements in safety, efficacy, and stability, its indications gradually expanded to further address potential poor quality-of-life indicators associated with short stature, propelling it to become an industry giant before being acquired by Roche at a premium valuation.

It must be acknowledged that the welfare or commercial insurance systems in European and American markets can serve as payers for rare disease drugs, providing a relatively favorable commercialization environment for foreign rare-disease biotech companies. However, in China, the primary payer remains the national medical insurance system; rare disease drugs that fail to gain reimbursement coverage often withdraw from the market due to their small patient populations.

For example, Vimizim (elosulfase alfa), a medication for mucopolysaccharidosis type IVA (MPS IVA), is withdrawing from the Chinese mainland market. While the Chinese market may not be substantial for pharmaceutical companies, its exit leaves domestic patients with no available treatment options. Vimizim was included in the preliminary list for the 2021 National Reimbursement Drug List (NRDL) negotiations, but the talks ultimately failed. It did not participate in the 2022 NRDL negotiations; consequently, the drug remains excluded from the national NRDL and is currently covered only by certain local medical insurance schemes and supplemental commercial health insurance plans (such as “Huimin Bao”).

Vimizim is prohibitively expensive and requires lifelong administration, with only a handful of patients able to afford it out-of-pocket, leading to its discontinuation upon expiration. Even for orphan drugs, pharmaceutical companies should actively strive to include their products in the National Reimbursement Drug List (NRDL) over the long term, provided they can demonstrate sufficient therapeutic value.

“Drugs for rare diseases with more than 5,000 diagnosed patients and over 3,000 treated patients in China should be considered for inclusion in the National Reimbursement Drug List (NRDL).” This was pointed out by Yu Lei, Head of Rare Diseases and Rare Hematological Disorders at Sanofi China, during a discussion at the 12th China Rare Disease Summit. “Inclusion of rare disease drugs in the national medical insurance scheme” was one of the key topics of the conference.

Currently, 70% of rare disease drugs already marketed in China are included in the National Reimbursement Drug List. However, as policy incentives and advancements in innovative drug R&D accelerate the domestic launch of high-cost rare disease therapies, the pressure to include these expensive treatments in the national medical insurance system is intensifying. In this context, special funds and policy-backed commercial insurance products, such as city-specific supplementary medical insurance (Hui Min Bao), can serve as additional payers beyond basic medical insurance.

“Huiminbao covers both healthy individuals and those with pre-existing conditions, giving it an inherent affinity for providing medical security for rare diseases,” said Wang Pingyang, Vice President of the Zhejiang Provincial Medical Insurance Research Association and Chairman of the Commercial Supplementary Medical Insurance Committee.

In Zhejiang Province, regarded as a benchmark for Huiminbao (inclusive commercial health insurance), the comprehensive reimbursement rate for certain rare disease medications reaches approximately 90%.

However, it is undeniable that the high cost and risk of rare disease drug development mean that excessive price reductions could dampen pharmaceutical companies’ incentives. In this regard,Wang Xiaohui, Co-founder and Chief Commercial and Operating Officer of Shufang Pharmaceuticals, stated, “For certain high-cost orphan drugs, it is essential to first open a door—for instance, by setting an overall reimbursement cap within the national medical insurance framework—so that patients with ultra-rare diseases can also qualify for insurance coverage. Subsequently, more reasonable multi-tiered security mechanisms for rare diseases should be explored.”

The commercialization and profitability of innovative drug companies can instill sustained confidence in the industry, and rare-disease innovative drug companies are no exception. Successful commercialization should be defined as achieving scaled sales revenue and stable profitability through drug sales. Chinese innovative drug companies specializing in rare diseases are exploring this path, with Shufang Pharmaceutical being one of them.

Shufang Pharma is not a typical biotech company; it primarily builds a commercially promising pipeline through rapid deal-making. Wang Xiaohui, the co-founder responsible for commercial operations, previously held positions at Actelion, Merck Serono, and Xi’an Janssen. Well-versed in regulatory affairs, government relations, and commercial channels, he has secured multiple partnerships for the company, including collaborations with Spain’s Minoryx, Akeso Biopharma, and Switzerland’s Santhera Pharmaceuticals. The most advanced asset is vamorolone, for which Shufang holds exclusive rights to develop and commercialize the drug in the Greater China region for Duchenne muscular dystrophy (DMD) and other rare disease indications.Vamorolone, a blockbuster drug for rare diseases, is expected to receive NDA approval from the U.S. FDA next month.

In 2021, the global market size for Duchenne Muscular Dystrophy (DMD) treatments exceeded USD 1 billion. China, with approximately 100,000 DMD patients, is one of the countries with the largest DMD patient populations worldwide. Vamorolone is considered the most promising candidate to replace standard treatment regimens. Shufang Pharmaceuticals has recognized the market potential and commercial prospects of this drug. Currently, its clinical development in China is progressing significantly. According to public announcements by the Center for Drug Evaluation (CDE), the vamorolone oral suspension jointly submitted by Shufang Pharmaceuticals is proposed for inclusion in the Breakthrough Therapy Designation program. The company stated that it plans to submit a New Drug Application (NDA) for vamorolone in China in the first half of next year.

“We regard vamorolone as an ‘anchor product’,“First, ensure that a product can be commercialized in China. Then, by collaborating with clinical experts and focusing on the disease areas of anchor products in the pipeline, expand the range of pipeline products. Forming multiple product portfolios in focused therapeutic areas can enhance operational efficiency,” said Wang Xiaohui, introducing Shufang Pharma’s commercialization strategy.

“The nervous system is the primary area of our current strategic focus,“Future resource accumulation around DMD will extend to pediatric genetic and metabolic diseases. At the same time, we are moderately laying out independent research and development, and there is already a self-developed product with a new target in the early pipeline.”

The commercial success of innovative drugs in China is closely tied to the national medical insurance system.Although high-value innovative drugs are at a disadvantage in being included in national medical insurance, rare diseases are often severe chronic conditions requiring long-term treatment. If effective pharmacological interventions significantly extend patients’ life expectancy, the prevalence of these diseases will gradually increase, leading to a cumulative patient population that grows like a “snowball.”From a temporal perspective, if pharmaceutical companies are willing to drive this “snowball” effect, they can ultimately achieve “volume-for-price” exchanges in the field of rare disease treatment, thereby creating conditions for drugs to be included in the national medical insurance reimbursement list.

Therefore, innovative drugs for rare diseases can establish a virtuous cycle, spanning project initiation, research and development, commercialization, and improved accessibility.

Previously,Langyu Group CEO Xiang YuIt was also stated: “Historically, perceptions of rare disease drug development have been biased, leading to the misconception that such endeavors yield only social value without economic returns... In contrast to the highly saturated fields of oncology and autoimmune diseases, rare disease drug development boasts higher success rates, shorter clinical trial durations, and faster regulatory approval.”It is precisely because of the various preferential policies for rare diseases that we have chosen to enter the market through this segment, accelerating product commercialization and thereby unlocking a larger market.”

Tangible economic benefits can better alleviate the difficulties faced by patients with rare diseases and also inject fresh vitality into the entire pharmaceutical industry.

References

1. https://mp.weixin.qq.com/s/XypfjzCuhVL_8_HycqEHNA

2. https://mp.weixin.qq.com/s/PA4C7Fx5yoFwJoRnIPE24g