Market Insight from

Immuno-oncology high prescriber survey reveals which R&D strategies the industry should be focusing on in the 7MM

High-prescribing physicians who routinely use immuno-oncology (IO) agents in their practice ranked the combination of co-inhibitory and co-stimulatory checkpoint modulation as the most important R&D strategy that the industry should be working on in the seven major markets (7MM): the US, France, Germany, Spain, Italy, UK and Japan (Figure 1).

Other very important R&D strategies include validating biomarkers to guide personalised IO therapy based on the likelihood of response and cytokine manipulation as supportive augmentation of other IO therapies.

Finding a balance between inhibition and strong stimulation of immune signalling is viewed as a great challenge while providing an important drug development opportunity.

For example, single-agent PD-1/PD-L1 checkpoint inhibition is often inadequate and combinations with co-stimulation of other checkpoints to promote further anti-tumour immunity would be highly desirable.

Bispecific antibodies are viewed as ideal to achieve this, as one antibody can engage in suppressing or augmenting controllers of immune activity simultaneously.

The aforementioned balance is key because while a strong anti-tumour response has apparent therapeutic advantages, it also carries a number of very significant side effects.

The intensity of these side effects may increase proportionally to the anti-tumour immune response and it should be reduced for this approach to translate in the clinic.

T-cell redirection is another version of the same strategy, wherein a bispecific antibody may target a tumour antigen while stimulating further immunity by bringing more T-cells into the tumour microenvironment.

Notable examples of this strategy include the late-stage anti-CD20/CD3 antibodies, Roche’s mosunetuzumab and Genmab’s epcoritamab for non-Hodgkin’s lymphoma.

The discovery of new biomarkers that limit IO therapy only to the most likely responders has been a hurdle for this field since the initial success of checkpoint inhibition in melanoma and limited success has only come about with the use of PD-L1 expression levels or measures of mutational burden/potential such as microsatellite instability.

As such, this is simultaneously an unmet need and an important strategy that physicians think should occupy much of the industry’s focus. Cytokine manipulation such as with interleukins or interferons has mostly fallen out of favour with physicians and key opinion leaders (KOLs) due to better options being available.

However, physicians believe that very interesting and promising biology for cytokine manipulation remains and that it just requires groundbreaking approaches to rejuvenate the field.

Recently, Nektar Therapeutics’ bempegaldesleukin has generated significant KOL excitement for its potential in melanoma when combined with Bristol Myers Squibb’s Opdivo, leading to high future sales projections by analysts.

Several variations of other R&D strategies were echoed by physicians at a lower frequency such as the need for head-to-head comparisons to pick the best among the drugs that are already marketed, investigation of the potential of time-limited therapy to alleviate long-term toxicities and the potential for sequential treatment wherein various mechanisms of action are introduced at different times.

For pharmaceutical industry data, comment and analysis, visit GlobalData's Pharmaceuticals Intelligence Centre.

Go to top

02/23/2024 23:26:44

Market Insight from

Using methotrexate may reduce the negative impact of high treatment-related costs on patients with myasthenia gravis

Myasthenia gravis (MG) is a rare autoimmune synaptopathy that is caused by the dysfunction of nerve cells and muscle fibres at the neuromuscular junction. The disease is characterised by pronounced muscle weakness and fatigue.

In the vast majority of MG patients, the disease is initially localised and limited to the eye muscles, causing drooping of the eyelid and double vision. Patients with untreated disease can experience severe weakness of respiratory muscles, leading to myasthenic crisis. In this situation, the patient can only survive through the use of mechanical ventilation and intubation.

Treatment of MG involves the administration of acetylcholinesterase inhibitors and corticosteroids. As it is an autoimmune condition, immunosuppressive therapies such as rituximab, tacrolimus and Alexion’s Soliris (eculizumab) have demonstrated efficacy in the management of patients with severe disease.

However, the high treatment-related costs associated with biologics mean that patients from underprivileged backgrounds can have difficulty accessing Soliris, despite the fact that the drug is approved in more than eight countries.

One potential solution to this issue is to encourage the use of drugs such as methotrexate, which has notable advantages over other widely available immunosuppressants, such as azathioprine and cyclosporine.

Methotrexate tablets are taken once weekly, while azathioprine and cyclosporine tablets are both administered once-daily. The potential teratogenicity of azathioprine is a subject of ongoing debate. Cyclosporine is associated with hypertension, gingivitis, renal dysfunction and impaired insulin metabolism.

Conversely, clinical trials have shown that methotrexate is a safe, effective drug that is well tolerated by young patients and in people with comorbidities such as rheumatoid arthritis and psoriasis. Another clinical advantage is the fact that methotrexate can be injected subcutaneously and intravitreally for ocular indications.

Methotrexate is an anti-neoplastic agent that prevents the proliferation of lymphocytes. In MG, these are responsible for the production of autoantibodies that inhibit the neurotransmission of acetylcholine, which is a key component of the autonomic nervous system.

Despite the widespread availability of generic methotrexate in countries such as the US, Italy, Germany and Switzerland, the lack of formal approval for MG restricts its use for this debilitating and potentially fatal condition.

Increasing the volume of clinical data to provide evidence of the drug’s efficacy and safety profile in people with MG could be an important step toward making the treatment more affordable for socioeconomically disadvantaged patients.

This is especially important for patients who are unable to be managed with non-pharmacotherapeutic strategies such as thymectomy and plasmapheresis.

For pharmaceutical industry data, comment and analysis, visit GlobalData's Pharmaceuticals Intelligence Centre.

Go to top

02/23/2024 23:26:44

Image: Goodwin partner Andrew Harrow

Image: Atomwise CEO and co-founder Abraham Heifets

Comment

What should the pharmaceutical serialisation sector be doing to protect against fake Covid-19 vaccines?

CEO of advanco Alf Goebel examines how the pharmaceutical sector can unite in the ongoing battle against fake covid vaccines and other counterfeit drugs. As a provider for level 3 item level serialisation, advanco was acquired by parabellum investments, led by founder and chief executive Rami Cassis in 2020.

CEO of advanco, Alf Goebel. Credit: advanco

The ongoing problem of counterfeit drugs has been brought to mainstream attention following the seizure of 3,000 saline-filled vials being sold as Covid-19 vaccines in China at the beginning of February 2021.

The police operation resulted in more than 80 group members being arrested, with reports stating that the group had been filling the vials with saline and passing them off as vaccines for many months.

Apart from the shocking human impact of this case – I am sure there will be people who pinned all their hopes on receiving this fake vaccine – it has highlighted once again the massive scale of drugs and medicine scams.

Although this case originated in China, I am sure that fake Covid-19 vaccines are being produced in multiple countries all around the globe at this very moment in time.

It is predicted that 10% of pharma products worldwide are counterfeit, with the global counterfeit drug market exceeding an eye-watering $75bn. Research further estimates that the death-toll caused as a result could increase to ten million people by 2050.

Further estimates by the World Health Organization show that between 72,0000 and 169,000 children may die from pneumonia every year after receiving counterfeit drugs, and that fake anti-malarial medication might be responsible for an additional 116,000 deaths.

During this time of a global pandemic, when people across all nationalities, age-ranges and backgrounds are genuinely worried about medical concerns, we are especially vulnerable to drug counterfeiters.

So, what can the pharmaceutical industry be doing to protect against these criminal acts?

Stricter enforcement

When it comes to pharmaceutical track-and-trace, even in developed and developing economies that have already laid out, or are in the process of laying out, the regulatory road map for serialisation, governments and enforcement agencies must ensure the legislation is in place to ensure it is being enforced.

The recent case in China has shown that criminal activity remains prevalent in these regions, and it remains relatively easy for the forgers to continue plying their trade.

Enforcement needs to be strict, sharp and ongoing – not only focusing on Covid-19 vaccines during this pandemic, but on all drugs and medical equipment.

Opening up the supply chain

It is important for product serialisation services to work together and encourage an open and secure supply chain, resulting in a supply chain that will minimise costs for pharmaceutical companies.

We are already seeing the advent of the virus accelerating the implementation of agile supply chain regulation, which will require a strong, industry-standard open interface and interoperability.

To do this, the hardware and the software among different vendors need to be much more aligned and should work much closer together.

Although, on the surface, this might seem a bold step within the pharmaceutical sector, we are already seeing some inroads being made, which will help to provide a solution to the dependency on the production of medication in China.

Moving forwards, trends to look out for include digital transformation in the serialisation sector, with increased usage of barcoding helping to reduce errors in dispensing in stressful periods.

Vaccines and test kits developed to detect the virus will need to continue to be supplied across the world quickly and efficiently - which requires more standardisation.

Even when more countries will change production strategies and localise, many drugs will continue to be manufactured in China and India, again emphasising the need for an efficient distribution system.

Stepping up ESG efforts

Environmental problems – a major topic for most industries across the world nowadays – can also be exacerbated by drug counterfeiters.

The pharmaceutical sector must abide by strict guidelines to meet environmental protection standards and reduce the amount of chemical waste and by-products that they produce. And of course, any waste products must be disposed of in line with strict regulations and guidelines.

In direct contrast, the producers of forged drugs often completely disregard the effect that the illegal disposal of toxic chemicals and waste materials can have on the environment around them – in much the same way they disregard the potential to kill people with their illegal products.

That is why I fully support the stepping up of ESG efforts within the serialisation sector specifically, and the entire pharmaceutical sector more generally. We at advanco are committed to our ESG efforts and would expect all other firms within pharmaceutical track-and-trace to also treat it as a cornerstone of their business.

Support of global ESG initiatives is an important step forward to stamping out the issue of fake drugs, whether these are fake Covid vaccines, or any other type of drug or piece of equipment. The UN Charter on sustainable development is a clear example of moves that are being established to ensure a safer and more responsible world which we can all enjoy.

Tight industry standards

The implementation of open standards is another crucial method in the fight against fake Covid vaccines and other drugs. The establishment of OPEN-SCS, the industry body responsible for promoting common standards across the pharma sector, is another solid step forward in the fight against fake medicines.

OPEN-SCS, of which advanco was a founder member, was formed in September 2014 and is a working group in the OPC Foundation, whose success speaks for itself.

Today, there are more than 4,200 suppliers, who have created more than 35,000 different OPC products, used in more than 17 million applications. The estimate of the savings in engineering resources alone is in the billions of dollars.

The seizure of the 3,000 fake Covid-19 vials at the start of February was, unfortunately, far from being a mere blip in the system. It is something we are likely to see repeated sooner rather than later, potentially in any country in the world.

However, by working together, I hope the pharmaceutical sector can provide substantial resistance to those who think it is acceptable to risk lives – and livelihoods – by peddling fake medicine.

Go to top

02/23/2024 23:26:44