The propionic acidemia therapeutic market is estimated to be valued at USD 600.6 Mn in 2024 and is expected to reach USD 1,016.6 Mn by 2031, growing at a compound annual growth rate (CAGR) of 7.8% from 2024 to 2031. Increase in research and development activities for developing newer treatments for propionic acidemia is a major factor anticipated to drive market growth. Several pipeline drugs are under development which upon approval will provide novel treatment options and boost market revenues.

Market Driver - Increasing Research on Gene Therapy and its Application to Metabolic Disorders

Gene therapy holds immense potential in treating various metabolic disorders including propionic acidemia by replacing the missing or defective genes. Recent breakthroughs in vector technology and gene delivery methods have enabled more targeted and reliable introduction of normal genes into the body's cells and tissues.

Scientists are developing viral as well as non-viral vector systems that can efficiently transport therapeutic genes to the liver cells, which is the primary site of pathogenesis in propionic acidemia. This can normalize the metabolizing process and prevent toxic buildup of substances that leads to various acute and long-term health complications.

Some of the key research institutes evaluating gene therapy approaches for propionic acidemia include NIH Rare Diseases Clinical Research Network, University College London, Mount Sinai School of Medicine and Massachusetts General Hospital.

A few early-stage human trials are also underway to assess safety and preliminary efficacy. If proven successful, gene therapy may emerge as a one-time curative treatment for propionic acidemia instead of life-long management with special diets and medicines. This growing research focusing on developing gene-based treatments for metabolic disorders like propionic acidemia is attracting more funding and investments in this domain.

Market Driver - Growing Focus on Rare Disease Markets

There is an increased emphasis on developing treatments for rare or orphan diseases. Regulatory agencies and governments across various countries are proactively supporting research on rare disorders through incentives such as tax credits, grant funding, fee waivers and market exclusivities. For instance, in the US, the Orphan Drug Act of 1983 aims to stimulate drug development for rare diseases by providing manufacturers with various benefits if the product is approved to treat a rare condition affecting less than 200,000 people.

The European Commission also recognizes rare diseases as a public health priority area and has implemented the EU Regulation on Orphan Medicinal Products to promote development of orphan drugs. Specialized funding programs like the Horizon Europe and increased scientific collaborations are expediting progress. Additionally, patient advocacy groups are playing a bigger role in raising awareness, catalyzing research and creating a conducive environment for industry participation in rare disease drug development.

There are also increased M&A deals involving small rare disease-focused biotechs which helps accelerate product pipelines. The rarity of individual rare disorders concentrates patient populations, making marketing and commercialization strategies more targeted and feasible. This industry evolution makes propionic acidemia an emerging therapeutic category attracting greater R&D investments.

Market Challenge - High Costs of Advanced Therapies Limiting Accessibility

One of the major challenges facing the propionic acidemia therapeutic market is the high costs associated with advanced therapy options such as gene and cell therapies. These innovative treatment approaches have promising potential to effectively manage and even cure rare metabolic diseases like propionic acidemia.

However, the extreme expense of researching, developing and manufacturing such complex gene and cell-based interventions means the end costs routinely run into the hundreds of thousands to millions of dollars per patient. While these high price points may be justified and economical from a traditional drug development perspective, they significantly limit treatment accessibility for patients.

Most national healthcare systems and private insurance providers have difficulty incorporating the costs of these new advanced treatments into their budgets. As a result, only a small subset of eligible patients who can afford the out-of-pocket costs or have sponsors willing to pay are able to access these potentially life-changing therapies.

The large price differential between older traditional treatments and cutting-edge gene and cell therapies threatens to worsen health inequities if not addressed.

Market Opportunity - New Advancements in mRNA Technology for Rare Metabolic Diseases

One promising opportunity for propionic acidemia therapeutic market is the ongoing progress in mRNA technology. Researchers are exploring the application of messenger RNA as a new platform for developing gene therapies to treat rare metabolic disorders. Unlike traditional gene therapies that rely on viral vectors, mRNA therapeutics could offer advantages in safety, scalability of manufacturing, and possibly lower costs over the long term.

Several biotech companies are conducting research programs using mRNA to deliver gene replacements for inborn errors of metabolism like propionic acidemia. Preliminary data from early studies have shown mRNA treatments may effectively restore missing or mutated enzyme activity in animal models.

Advancements that result in safe, effective, and affordable mRNA therapies translatable to humans could open up a major new treatment option for propionic acidemia. Widespread application of mRNA technology holds potential to address one of the key current challenges facing market adoption of advanced therapies - high costs limiting accessibility. Successful development of mRNA gene replacements could re-shape the entire rare disease therapeutic landscape in the coming years.

Propionic Acidemia is typically treated via a step-wise treatment approach consisting of multiple lines of therapy targeting different stages of the disease. For mild cases, prescribers typically start with nutritional interventions like restricting protein intake and supplementing with carnitine and glycine.

As the condition progresses, drug therapy is initiated. For acute metabolic crises, intravenous antibiotics like cefotaxime (Claforan) are prescribed to prevent infection while sodium benzoate (Proglycem) is used to help remove toxic metabolites from the body. Prescribers may also use sodium phenylbutyrate (Buphenyl) to induce the formation of alternative metabolic pathways.

In more severe or chronic cases, hematopoietic stem cell transplantation (HSCT) is considered. Prior to HSCT, prescribers aim to minimize toxic metabolite levels using the above medications. HSCT has shown promise in arresting further progression if performed early.

Other important factors affecting treatment decisions include a patient's overall clinical status, organ involvement, nutritional management responsiveness, and metabolic control achievability using medication. Prescribers closely monitor various markers to assess treatment effectiveness at each disease stage.

Propionic Acidemia has four primary stages - Neonatal, Early Childhood, Late Childhood and Adulthood.

Neonatal stage presents within the first few days of life with lethargy, poor feeding and vomiting. Treatment involves hospitalization, intravenous fluids, antibiotics to prevent infections and supplementary carnitine.

In early childhood, metabolic control is crucial to prevent further complications. A specialized low-protein diet with supplements to assist protein breakdown is initiated. Medium-chain triglyceride (MCT) oil provides an alternate energy source. Drugs like sodium benzoate and glycine help eliminate toxic byproducts.

During late childhood, in addition to lifelong special diet and medications, ammonia scavenging drugs like sodium phenylbutyrate and arginine are preferred. They work by conjugating nitrogen and facilitating excretion. Hospitalization is needed during stress periods or if metabolic imbalance occurs.

In adulthood, the standard treatment comprises of dietary therapy with low protein foods supplemented by essential amino acids, carnitine, B12, glycine, MCT oil, sodium benzoate and sodium phenylbutyrate. While medications help control acute episodes, long-term complications involving heart, brain and muscles may arise needing multidisciplinary management. Liver and kidney transplant is considered in severe, treatment-resistant cases to cure the underlying defect.

Product Innovation: One of the most effective strategies adopted by players has been continuous product innovation. In 2017, Synlogic launched SYNB1618, a synthetic biotic designed to degrade propionate as a potential treatment for propionic acidemia. Clinical trials are currently underway. Earlier in 2013, Horizon Pharma launched BUPHENYL tablets, the first FDA approved drug to treat urea cycle disorders including propionic acidemia.

Tie-ups & Partnerships: Companies have formed strategic collaborations with leading academic research centers to gain access to new drug candidates and pipelines. For example, Synlogic collaborates with Massachusetts General Hospital. In 2018, Synlogic and Mirum Pharmaceuticals co-developed SYNB8802, an oral therapy for urea cycle disorders and organic acidemias.

Acquisitions: Larger players have strengthened their portfolio through acquisitions of smaller biotechs. In 2019, Chiesi Farmaceutici acquired Orphan Technologies, acquiring rights to commercialize Orphan Technologies' product Carglumic acid for propionic acidemia in the EU. This expanded Chiesi's global presence.

Patient Advocacy: Players conduct patient advocacy programs to raise awareness and collaborate with foundations. Synlogic works closely with patient networks like MMA International and Organic Acidemia Association. This helped gain patient support for ongoing clinical trials.

Insights, By Therapeutics: Advances in Gene Therapy Drive its Rising Adoption

In terms of therapeutics, gene therapy is expected to hold 55.2% share of the market in 2024, owing to major advances in this field. Gene therapy offers the potential for a 'one-time' curative treatment by delivering therapeutic genes into target cells of patients to compensate for mutated genes that cause disease.

Researchers have made significant progress in developing effective gene therapies for Propionic Acidemia. Specifically, research is underway to develop gene therapies that can deliver 'healthy' copies of the PCCA or PCCB genes directly into liver cells, enabling them to process propionyl-CoA naturally.

Additionally, new delivery methods allow for more targeted and efficient gene delivery compared to earlier techniques. As the technology matures, gene therapy is gaining recognition as a viable treatment option instead of standard of care enzyme replacement therapies that require frequent administrations.

Insights, By Molecule Type: Convenience Drives Popularity of Small Molecule Therapeutics

In terms of molecule type, small molecules are expected to hold 51.6% share of the market in 2024, due to the convenience they offer over biologics in administration. Small molecule therapies for propionic acidemia mainly aim to lower toxic metabolite levels or help bypass blocked metabolic pathways. They are easier to develop, manufacture, store and administer compared to biologics.

For patients, they provide more user-friendly options in terms of route of administration like oral pills that do not require frequent hospital visits or healthcare professional involvement. This improved convenience is a major driver of patient preference and adherence for small molecule therapies, resulting in their increased usage in propionic acidemia management.

Insights, By Administration Route: Oral Route Gains Traction Due to Ease of Use

In terms of By Administration Route, the Oral route contributes the highest share due to the unparalleled ease and comfort it offers patients over other routes. Oral medications have clear advantages for long-term conditions like Propionic Acidemia, which require lifelong treatment. They are generally perceived as more natural and discreet by patients compared to alternatives involving needles or intravenous access. Additionally, oral drugs allow for self-administration at home without much training.

This empowers patients and increases adherence. The non-invasive nature of oral therapies also helps healthcare providers easily transition pediatric patients to adult therapies. Given these major benefits, more Propionic Acidemia treatments are being developed as oral regimens, driving the segment's growth.

Propionic acidemia affects approximately 1 in 100,000 people globally. Current treatments rely on strict dietary management and supplements, but gene therapy is expected to revolutionize the market by offering more comprehensive treatment options.

The major players operating in the propionic acidemia therapeutic market include HemoShear Therapeutics, LogicBio Therapeutics, Roche, Astellas Pharma, Moderna Therapeutics, Homology Medicines, Inc., Abeona Therapeutics, Inc., and Ultragenyx Pharmaceutical Inc.

• In July 2024, HemoShear Therapeutics announced a breakthrough in gene therapy targeting Propionic Acidemia. The company’s research shows a potential 50% reduction in harmful metabolites, offering hope for long-term disease management.
• In October 2023, LogicBio Therapeutics completed its Phase I trial for a gene-editing treatment for Propionic Acidemia, marking a significant step toward precision medicine.
• mRNA-3927 is Moderna's investigational mRNA therapeutic for Propionic Acidemia (PA). It utilizes mRNA technology to encode for the alpha and beta subunits of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). This enzyme is crucial for addressing the underlying genetic cause of Propionic Acidemia, where patients have mutations in the genes responsible for the production of this enzyme. Moderna's therapy aims to restore the enzyme's function, helping to reduce the accumulation of harmful metabolites​.
• Gene therapy: Companies like Homology Medicines and Abeona Therapeutics are focusing on gene therapies to address genetic defects causing the disorder. Homology Medicines works on gene therapy and gene editing programs for conditions like PKU and Hunter syndrome, while Abeona Therapeutics focuses on gene therapies for lysosomal storage diseases and ophthalmic conditions​.

• By Therapeutics
  • Gene Therapy
  • Enzyme Replacement Therapy
• By Molecule Type
  • Small Molecules
  • Biologics
• By Administration Route
  • Oral
  • Intravenous