Ordering new and rare medicines from Europe

Daraxonrasib by Revolution: a new development in the treatment of pancreatic cancer

Daraxonrasib is a new targeted drug for the treatment of pancreatic adenocarcinoma carrying the KRAS G12D mutation, one of the most common and most aggressive forms of pancreatic cancer. It has been developed as a selective inhibitor of the mutated KRAS protein, which makes it possible to act directly on a key driver of tumour growth and potentially to improve survival in patients who today have very few effective options.

The main focus at present is on late-phase clinical trials, whose results will form the basis for approval submissions to the regulators in the USA (FDA) and the EU (EMA). Once these trials are successfully completed, the developer plans to seek accelerated review of the applications, since the disease in question is severe, hard to treat and carries a high unmet medical need.

For patients this means that within the next few years a fundamentally new treatment option may become available — one aimed at a specific genetic mutation of the tumour rather than at standard chemotherapy alone. Doctors and patients are already following the status of the trials and are preparing for a situation in which, if the drug is approved in the USA and the EU, access to molecular testing for the KRAS G12D mutation will be decisive in selecting those who can genuinely benefit from the treatment.

Anktiva: a new option for bladder cancer on the horizon

The EMA has recommended conditional approval of the new drug Anktiva (nogapendekin alfa inbakicept) for some patients with non-muscle-invasive bladder cancer who do not respond to standard BCG therapy. This new drug, with its hard-to-pronounce name and novel targeted mechanism, will most likely reach the EU market soon: nogapendekin alfa inbakicept is the first interleukin-15 (IL-15) receptor agonist.

The European Medicines Agency (EMA) has come out in favour of conditional approval of Anktiva® for the treatment of patients with non-muscle-invasive bladder cancer (NMIBC). It is a fusion protein which, as an IL-15 receptor agonist, activates and stimulates the proliferation of natural killer cells, CD8⁺ T cells and memory T cells. In this way Anktiva strengthens the anti-tumour immune response.

According to the EMA, bladder cancer, with 200,000 new cases a year, is among the most common cancers in Europe. Most patients are diagnosed with non-muscle-invasive bladder cancer. Standard treatment involves surgical removal of the tumour followed by intravesical instillations of the BCG vaccine (Bacillus Calmette-Guérin). This is intended to activate the immune system and destroy the remaining cancer cells. In many patients, however, the disease recurs.

For patients who do not respond (or are unlikely to respond) to BCG therapy there have so far been no approved treatment options, and the bladder often had to be removed. With the arrival of Anktiva the situation may change: the drug is intended precisely for such therapy. The new active component is administered together with BCG as intravesical instillations once a week for six weeks, and is then used as maintenance therapy

Anktiva is given together with BCG as a course of instillations followed by maintenance therapy, strengthening the immune response against the tumour. In a study of 100 patients, the combined treatment produced a response in 71% of patients lasting an average of 27 months, with the expected local and systemic side effects (dysuria, haematuria, urinary tract infections, fever and others)

Next-generation weight-loss drugs: what to expect in the coming years

Why everyone is talking about incretins right now

In recent years the treatment of obesity has changed dramatically: incretin-based drugs have come to the fore — above all GLP-1 receptor agonists and their combinations. These medicines do not simply «suppress appetite»; they act on the body's hormonal response: they reduce the feeling of hunger, slow gastric emptying and improve blood sugar control. As a result, many patients lose 10–20% or more of their initial body weight, provided that they also change their diet and lifestyle.

Some incretin drugs are already available on the market, while several more important molecules and formulations are on the way. Below is an overview of the key new developments that patients and doctors should know about.

GLP-1-based weight-loss tablets

Oral semaglutide (Wegovy in tablet form)

Until recently semaglutide was known mainly as an injectable drug (Ozempic, Wegovy). The tablet form of semaglutide for the treatment of obesity has already been approved in the USA and has shown weight loss comparable to the results achieved with injections. This is an important step for patients who are afraid of injections or tolerate them poorly.

In the coming years the availability of tablet semaglutide is expected to expand to other markets, including the countries of Europe. For healthcare systems this means a wider choice of treatment options: the doctor will be able to select both the dose and the form — injections or tablets — depending on the individual patient.

Orforglipron (Eli Lilly)

Orforglipron is a new once-daily weight-loss tablet that also belongs to the incretin class. In clinical trials the drug produced a reduction in body weight of roughly 6–8% and demonstrated better efficacy than oral semaglutide.

Orforglipron is currently under review by the regulators in the USA. The manufacturer has provisionally indicated a price from 149 dollars a month at the initial stage. If the drug is approved and subsequently reaches the US and EU markets, it will become another important option for people with obesity who need effective yet convenient tablet therapy.

New injectable drugs

Retatrutide — a triple agonist (GLP-1/GIP/glucagon)

Retatrutide (Eli Lilly) is one of the most talked-about molecules in the treatment of obesity. It is a triple agonist that acts simultaneously on the GLP-1, GIP and glucagon receptors. In phase II trials the drug produced a reduction in body weight of up to 28–29% of the initial weight — comparable to the effect of bariatric surgery, but without an operation.

Retatrutide is currently in the late stages of clinical trials. If the results are confirmed, it is expected to be one of the most powerful anti-obesity drugs: it could become an option for patients with severe obesity and metabolic complications in whom standard therapy has not worked.

New regimens of semaglutide and tirzepatide

Alongside fundamentally new molecules, manufacturers are actively developing drugs that are already well known:

• semaglutide (Ozempic, Wegovy);

• tirzepatide (Mounjaro, Zepbound), a dual GIP/GLP-1 agonist.

Combination and longer-acting formulations are currently being tested, which allow injections to be given less often while maintaining or even strengthening the effect. This matters for treatment adherence: the less often a patient has to think about the drug, the greater the chance that they will complete the full course.

Combinations and the «next wave» of drugs

CagriSema and other combinations

A separate line of development is the combination of semaglutide with other active substances. One example is CagriSema, in which semaglutide is combined with a further active molecule. Such combinations are being developed above all for difficult cases: patients with marked obesity and severe concomitant diseases.

The aim of these regimens is to increase weight loss, improve control of glucose and fat metabolism and reduce cardiovascular risks. In the longer term, combinations of this kind may become the standard of therapy in high-risk patients, for whom a simple «minus 10% of body weight» is no longer enough.

New incretin molecules

In parallel, companies are working on new oral and injectable drugs that also act on the incretin system, but that:

• produce a more pronounced and more stable weight-loss effect;

• cause fewer gastrointestinal side effects;

• make it possible to individualise therapy (choice of dose, dosing frequency and formulation).

This means that in the coming years doctors will have not just one or two drugs «to choose from», but a whole range of agents that can be combined with diet, physical activity and other forms of treatment.

Important: these are drugs for the treatment of obesity, not «magic pills»

Despite the loud headlines in the media, all of these medicines are serious medical therapy for the treatment of obesity and the diseases associated with it, not «beauty pills».

• They are prescribed for strictly defined indications: usually for a BMI ≥30, or ≥27 in the presence of concomitant conditions (type 2 diabetes, arterial hypertension, dyslipidaemia and others).

• Treatment must take place under the supervision of a doctor (an endocrinologist, dietitian or obesity specialist).

• An essential condition is a change of diet, increased physical activity and work on eating behaviour. Without this the effect will be weaker and less lasting.

• Side effects are possible (nausea, vomiting, diarrhoea, constipation, headache and others), so individual dose selection and monitoring are important.

Incretin drugs open up a completely new level in the treatment of obesity, but they do not do away with the basic principle: a lasting result is only possible when medication is combined with a change of lifestyle and regular medical supervision.