1. Insulin inhalers

According to data from the World Health Organization (WHO), there are approximately 10 million patients with type 1 diabetes worldwide who require insulin injections to survive. Some patients with type 2 diabetes also require medication.

Modern technologies make injections safe, convenient, and almost painless, but it is still an unpleasant process, also from a psychological point of view. The idea of creating a new approach to insulin administration had been brewing for a long time. In fact, the first insulin inhalation device was tested back in 1924, just three years after the medicine itself appeared. Unfortunately, the technology of those years did not allow for the creation of effective inhalation methods.

The idea was revisited in the 1980s, when a small company called Nectar Therapeutics developed a technology that allowed insulin to be produced in the form of fine particles suitable for use in inhalers. The license for this invention was purchased by Pfizer, which began the long process of developing the world's first insulin inhaler.

The process of creating the device took a decade and a half, and the developers encountered a number of technical problems, primarily related to the need for accurate dosing of the medicine. Nevertheless, the device worked and showed sufficient efficacy and safety. It seemed that Pfizer had a product that could radically change the market, so high hopes were pinned on it.

In 2006, Exubera was introduced — the world's first insulin inhaler, designed to replace constant injections and make life easier for patients, but it almost immediately faced a resounding failure. There were several reasons for this.

[caption id="" align="alignnone" width="1920"] Exubera inhaler. Source: Science Museum Group[/caption]

Firstly, the cost of inhaled insulin turned out to be several times higher than usual, and given that this medicine is already significantly more expensive in the US than in other countries, this became a very serious deterrent. Insurance companies refused to reimburse patients' expenses, which sharply reduced potential interest in the new product.

Secondly, inhalers could not be called convenient or compact. For example, before dinner at a restaurant, it was easier for a person to give themselves an injection than to publicly manipulate a massive device, which the press sarcastically compared to a drug paraphernalia.

Finally, according to some experts, the company did a poor job of positioning the product. The medicine was promoted as a universal solution for all patients, most of whom were not willing to overpay for relatively conditional comfort with similar effectiveness. At the same time, the medicine demonstrated high effectiveness in treating obese patients in whom injectable insulin is retained in the subcutaneous tissue. However, the company did not conduct the necessary clinical trials and did not target this audience. Exubera was withdrawn in 2007 after being on the market for about a year, and Pfizer had to write off more than $3 billion in losses.

The failure of the American corporation did not stop the French company Sanofi from making a new attempt to bring inhaled insulin to market. Sanofi entered into an agreement with the American company Mannkind, which developed the medicine and inhaler Afrezza. The device was much more advanced than Exubera: more compact, more convenient, and more accurate.

[caption id="" align="alignnone" width="797"] Affreza inhaler. Source: everydayhealth.com[/caption]

Afreza proved to be more successful than its American counterpart, but Sanofi failed to learn from Pfizer's mistakes. The cost remained high, and it was not possible to reach an agreement with insurance companies. In addition, there were reports that the medicine could cause lung problems. Sales for the whole of 2016 amounted to only $7.5 million, so Sanofi eventually withdrew from the project. Mannkind continued to work on the project, but for the whole of 2024, sales amounted to a very modest $64 million by insulin market standards. However, it is too early to completely abandon the idea of inhaled insulin. Despite two unsuccessful attempts, insulin inhalers may become the new standard in the future.

1. Addyi

The segment of medicines for treating sexual dysfunction in men is very extensive. The most famous brand, Viagra (sildenafil), has become one of the most recognizable brands in the history of the global pharmaceutical market and has practically become a household name. Naturally, many companies dreamed of repeating this success. One of them was Sprout Pharmaceuticals, a small American startup that was serious about radically changing the pharmaceutical market.

Sprout's plans were ambitious, and the idea was revolutionary. Viagra and other similar medicines are only available to men, which means that there is potentially an unoccupied niche in the treatment of sexual dysfunction (hypolibidemia) in women. The first company could strike gold if it reached this. All that remained was to create the product itself. Addyi (flibanserin) was a contender for this role.

[caption id="" align="alignnone" width="905"] Addyi advertisement, source: Addyi HCP[/caption]

It seemed that Addyi was destined to repeat the success of Viagra, even the history of its appearance was very similar. Like sildenafil, which grew out of the development of a medicine for the treatment of hypertension and angina pectoris, flibanserin was originally created as an antidepressant. And just as with sildenafil, the reason for the change in research focus was the side effect of increased libido in women. However, Boehringer Ingelheim, which originally developed the medicine, abandoned it after a negative assessment by the FDA, and Sprout ultimately acquired the rights to the product.

The chances of a small company obtaining approval were expected to be significantly lower than those of a multinational giant, but management had a sophisticated plan in place for this scenario. Sprout resubmitted its application, providing data from new studies, but the FDA again refused, citing an uncertain benefit-risk ratio. The company appealed, and an advisory board was created to resolve the dispute, which ruled in favor of Sprout.

One of the reasons for the FDA advisory board's positive decision was that the diagnosis of hypolibidemia was first divided into male and female only in 2013 in the DSM-5 nosological system. The newly emerged diagnosis of female sexual interest/arousal disorder (FSIAD) had a very weak theoretical and practical basis.

One of the most controversial aspects of the FDA situation was that some members of the expert council were affiliated with the manufacturer, including receiving direct funding from the company.

In 2015, Sprout became a division of Valeant Pharmaceuticals (now known as Bausch Health) in a deal worth $1 billion. However, four years later, the original owners bought the company back for the same amount.

To promote Sprout, the company decided to enlist the support of not only experts but also the public, launching the “Even the Score” campaign and positioning the product as “Another step toward gender equality.” The company also enlisted the support of several women's organizations.

[caption id="" align="alignnone" width="2700"] Even the Score campaign logo. Source: PR Newswire[/caption]

The Addyi marketing campaign caused a huge stir, though not quite the one they were hoping for. People from the medical community, patient organizations, feminists, and even politicians spoke out against it. Many doctors criticized the FSIAD diagnosis itself and believed that psychological problems should be addressed first, rather than resorting to ineffective medicine treatment. The Even the Score campaign also raised a number of questions. Many argued that Sprout was exploiting the issue of gender equality solely to boost sales.

Despite significant investments in marketing, lobbying efforts, and addressing important social issues, the result was a resounding failure. The manufacturer, which expected to sell at least 1 million prescriptions per year in the US market, faced a different reality: in the first year, this figure was only 4,000, and after 10 years, it barely reached 400,000. For comparison, more than 3 million prescriptions are written annually for sildenafil alone in the US.

Interestingly, a similar product was developed and launched on the market in our country. In February 2022, the peptide medicine Desirix from the company of the same name received a registration certificate in the form of a nasal metered spray. In August of the same year, sales of the product started in the retail market, but it is still too early to talk about market success. According to the database “Audit of retail sales of medicines in Russia (total sell-out)” from the analytical company RNC Pharma, in 2024, just over 8,000 packages of the medicine were sold for a total of 31 million rubles (at retail prices, including VAT). Compared to 2023, the growth rate was 26% in real terms and about 9% in ruble terms. At the beginning of 2025, the medicine remains a purely niche product, with 1,650 packages sold in January-April for a total of 11.6 million rubles.

3. Glucose meters — a potential failure for Apple?

The third case cannot yet be unequivocally called a failure. The company has spent a significant amount of money over the past 15 years and has not yet achieved results, but this is more likely due to regulatory opposition. We are talking about glucose meter technology built into Apple smartwatches.

Apple first began developing blood sugar measurement technology back in 2010. At that time, the latest iPhone model was the fourth generation, Steve Jobs was still alive, and the first Apple Watch model was still five years away. It was then that the corporation acquired RareLight, a startup specializing in non-invasive glucose measurement technology.

It is unknown when work began on integrating a glucometer into the Apple Watch, as the company carefully conceals its internal documentation. There is no data on the actual costs incurred, but insiders say the amount could be up to a billion dollars. It is known that working prototypes already exist, but the manufacturer has encountered a very serious obstacle — resistance from the US regulator.

[caption id="" align="alignnone" width="896"] Sensor diagram from Apple patent. Source: Apple Insider[/caption]

The FDA's position is that non-invasive glucometers, especially those built into smartwatches, may pose a health risk to users, as even the most advanced non-invasive blood sugar measurement technologies cannot yet match the accuracy of “traditional” devices. Any malfunction in the sensors or software could result in the patient being misinformed about their condition.

It is likely that sooner or later Apple will achieve its goal and the FDA will issue approval for non-invasive glucometers in smartwatches. However, the big question is whether this will be the breakthrough the company was hoping for. It is known that competitors such as Samsung and Xiaomi are also actively developing in this area. Specialized companies are also actively involved — in 2024, the American medical technology manufacturer Dexcom received approval to sell its biosensor, which is as close as possible in its properties to non-invasive devices and is integrated with a smartphone.

Thus, Apple may lose its most important advantage — time. Competitors are closely monitoring Apple's actions, and it is quite possible that by the time the regulator makes a positive decision, they will already be ready to flood the market with their own devices with similar functionality.

Moreover, smartwatches with blood glucose monitoring functionality are already available today. There are many models with this claimed functionality on any marketplace, but they do not have medical device status, provide relatively low measurement accuracy, and can generally only be considered as functional toys.