DDW’s Megan Thomas looks at how different diseases will benefit from the success of therapeutic antibodies.
Monoclonal antibodies (mAbs) are a type of targeted drug therapy, and as such are often used to treat cancer. Alongside surgery, radiation and chemotherapy, antibody-based immunotherapy is considered to be a main component of cancer therapy1. This is not only made clear by the fact that the global cancer mAbs market size was valued at $55.6 billion in 2021, and is projected to reach $106.8 billion by 2031, growing at a CAGR of 7% from 2022 to 20312, but is also reflected in data by The Antibody Society, which shows that of the over 100 approved mAbs, around 40% are for cancer3.
Data highlights include results from Purple Biotech, which revealed positive new results in March 2023 from exploratory analyses conducted as part of a Phase I dose escalation study into CM24 plus nivolumab for advanced cancer. Additionally, interim results from an ongoing Phase I/II trial for Aulos Bioscience’s monoclonal antibody AU-007 were positive, showing that AU-007 is well tolerated in patients with unresectable locally advanced or metastatic cancer and there are early signs of anti-tumour activity.
The approval of mAb bamlanivimab for Covid-19, which took a record time of only eight months from discovery to dosage, was a landmark moment for this field, and this is reflected in the prevalence of therapeutic antibodies when it comes to treating Covid-19. The Antibody Society’s data confirmed that 3.63% of the approved mAbs were for the treatment of Covid-19, which is significant when considering that it has overtaken diseases such as Alzheimer’s, which has been studied for much longer.
What is particularly noteworthy when it comes to the mAbs being developed and approved for Covid-19 is drug repurposing, showing the scope of future treatments with mAbs. For instance, in 2022, Cyxone, a Swedish clinical stage biotech company developing disease modifying therapies for diseases such as rheumatoid arthritis, used its previously demonstrated favourable safety and tolerability profile for its drug candidate Rabeximod in the Clinical Study Report from its exploratory Phase II study in Covid-19 patients.
Earlier in 2023, a mAb to prevent Covid-19 in vulnerable patients, AZD3152, entered clinical trials less than 12 months after its discovery. AstraZeneca initiated the SUPERNOVA Phase I/III trial of AZD5156 (a combination of AZD3152 and cilgavimab) in pre-exposure prophylaxis of Covid-19, following the company licensing AZD3152 from RQ Bio in May 2022. The work is continuous for this disease target.
While previously mentioned that approved mAbs for Alzheimer’s Disease are less than that of Covid-19, this is not to say that the development in this area is insignificant. The 2.72% reflects two approved mAbs for the disease: aducanumab (Aduhelm) and lecanemab-irmb (Leqembi, Eisai), the latter of which was approved earlier this year.
The FDA approved Biogen’s regulatory application for the use of aducanumab in the treatment of Alzheimer’s disease, which reduces the build-up of beta-amyloid from brains – a hallmark of the disease. At the time, aducanumab was the first new Alzheimer’s drug in nearly 20 years. On 6 January 2023, the FDA approved lecanemab-irmb via the Accelerated Approval pathway for the treatment of Alzheimer’s disease.
In terms of arthritis, rheumatoid arthritis reflects 2.72% of the mAbs currently approved for treatment, while psoriatic arthritis reflects 9.09% of approved mAbs3. The global arthritis monoclonal antibodies market grew from $49.44 billion in 2022 to $53.81 billion in 2023 at a compound annual growth rate (CAGR) of 8.8%4.
The following drugs have been approved by the FDA for the treatment of rheumatoid arthritis: adalimumab (Humira), golimumab (Simponi), infliximab (Remicade), sarilumab (Kevzara), tocilizumab (Actemra), rituximab (Rituxan), abatacept (Orencia), certolizumab (Cimzia), and etanercept (Enbrel)5.
For psoriatic arthritis, approved treatments include: Adalimumab (Humira), Certolizumab (Cimzia), Etanercept (Enbrel), Golimumab (Simponi), Infliximab (Remicade), Brodalumab (Siliq), Guselkumab (Tremfya), Ixekizumab (Taltz), Risankizumab (Skyrizi), Secukinumab (Cosentyx), Tildrakizumab (Ilumya), and Ustekinumab (Stelara)6.
A large element of the success of Covid-19 therapeutic antibody treatment was scientists’ ability to repurpose drugs and findings from previous work, as is evident with the previous example of Rabeximod for rheumatoid arthritis. The foundations are solid and there is plenty of promise for using these therapies for rare diseases, an area which also highlights the significance of umbrella trials when it comes to therapeutic antibodies.
It is important to remember that when it comes to rare diseases, by nature they are highly specific and in general, have no cure. Often, symptom management is the end-goal with rare diseases. Similarly, mAbs have the potential to be highly specific and targeted, making them a natural pillar for the development of treatment for rare disease. In addition, their low toxicity mean that long-term treatment is possible7.
A prime example of repurposing for rare disease is Eculizumab, which targets the C5 protein. Originally, it was used to treat Paroxysmal Nocturnal Haemoglobinuria (PNH), a blood disease7. However, it also has applications in the kidney condition Atypical Haemolytic-Uremic Syndrome (AHUS) and the neuromuscular disease Myasthenia Gravis (MG)7.
DDW Volume 24 – Issue 3, Summer 2023 – Therapeutic Antibody Guide