China News Service, Beijing, March 25 (Liu Yi) Cell and gene therapy has shown potential in the treatment of many diseases such as cancer, genetic diseases and infectious diseases, and has received widespread attention.

For example, the China Drug Regulatory Science Action Plan has long included cell and gene therapy as a priority area of ​​regulatory scientific research.

  In order to comprehensively and deeply describe the development of gene therapy, KPMG recently released the "One Time Curing" Gene Therapy Report (hereinafter referred to as the "Report"), which covers the technical difficulties of gene therapy, market challenges faced by biopharmaceutical companies, investment mode, etc.

 three puzzles

  The "Report" believes that R&D and production technologies are still immature, and gene therapy faces three problems.

  - Drug delivery is the main technical obstacle.

Manufacturers still struggle to determine the optimal dose to deliver therapeutic effects to target tissues while minimizing toxicity and immunogenicity concerns.

Dr Alasdair Milton, general manager of KPMG's strategic life sciences division, said that delivery via a virus was the most common method, and recombinant adeno-associated virus (rAAV) was the "preferred" vector, at least for in vivo administration.

  The analysis also believes that about 70% of the current "one-step cure" gene therapy clinical trials use rAAV for delivery.

Scientists have been working to improve the rAAV genome due to slow startup and limited vector capacity.

  - Production and supply chains are the main drags.

Gene therapy is complex to produce, still requires manual operations, and is very expensive.

Yu Zilong, head of life sciences industry at KPMG China, said some companies have strengthened their control over supply chains by investing in their own production facilities and independent production capacity.

But this strategy only works for big biopharma companies with deep pockets, while smaller biotech companies that dominate the cell and gene therapy space remain very dependent on outside suppliers.

  -- The effects of gene therapy are still fraught with uncertainty.

Dr. Alasdair Milton pointed out that in reality, scientists are still grappling with the challenges related to the persistence of gene therapy, which also raises the question of whether gene therapy can actually "cure" the disease.

In childhood diseases such as Duchenne dystrophy, for example, cell metabolism and gene therapy may lose efficacy in certain tissues, such as muscle, as children age.

  Dr. Alasdair Milton further quoted the "Report" as saying that polygenic genetic diseases often have multiple genetic factors as well as environmental factors, lifestyle factors and other complex factors, and it is very difficult to use gene therapy.

At the same time, polygenic genetic diseases often have mature standards of diagnosis and treatment, and some of these treatment options are low-cost, which has become a commercial resistance affecting gene therapy.

In the foreseeable future, "one-step cure" gene therapy will remain largely limited to a small number of single-gene genetic diseases.

  five challenges

  The report pointed out that although the development of treatments for single-gene genetic diseases is very scientifically attractive, these diseases are often rare diseases with narrow patient populations.

To achieve commercial success in this area and bring potentially revolutionary treatments to patients, companies need to address five challenges.

  First, they faced the question of "where to start."

Yu Zilong explained that companies must understand the underlying etiology, biological complexity and natural history of the target disease in order to design appropriate basic research and clinical protocols.

  Secondly, as a short-term niche market, the "first-mover advantage" is particularly prominent in the "one-step cure" gene therapy industry, and whether it can be the first to enter the market will initially determine the success or failure of the business.

  The third key question is whether the company can strengthen its R&D and management capabilities to deal with future risks so that its revenue can be sustainable in the long term.

The report suggests that, in addition to launching follow-up treatments for patients, companies can track and focus on diseases that are pathologically similar, such as two genetic diseases caused by a defect in the same gene.

  Reaching early and maintaining close contact and communication with key stakeholders such as patients, healthcare providers, and payers is also a challenge, given the complexity and technological barriers to entry in the field.

  Yu Zilong reminded that it is crucial to establish an appropriate team, which should include researchers, regulatory experts in coordination with relevant regulatory agencies, manufacturing teams, supply chain and distribution teams, medical liaison officers for patients, and science communication experts for the general public. , pricing and market access experts, payer-facing health economics and outcomes research experts, genetic consultants, and more.

  In view of the challenges in the development, manufacturing and commercialization of gene therapy, the "Report" believes that "active and prudent, diversifying investment, persevering to the end, and pursuing long-term success" is more in line with the actual investment and management strategy of the current industry.

(over)