Drug approvals are often the outcome of vicious fights between big and mid-level actors in the pharmaceutical industry. Patients that cannot have access to efficient and innovative drugs are the ultimate victims of such fights.
A medical breakthrough was scheduled to disrupt the European pharma market in 2017. The drug, Aplidin developed by Pharma Mar (PHM.MC), is a life-prolonging treatment for cancer patients suffering from multiple myeloma that uses marine-based antitumor molecules. The life prolonging drug could have opened the door to other potentially efficient treatments but instead, it was blocked by bureaucratic red tape during the authorization process of the European Medicines Agency (EMA). Their competitors are Pharma giants, companies whose drugs were swiftly approved for market distribution. These giants are responsible for nearly half of the global market share.
PharmaMar vs. Big Pharma
Over 40,000 multiple myeloma patients in Europe alone could benefit from a treatment that can prolong their life. However, rejection of that first-in-class drug came as a surprise, including for patients, after a positive review by EMA’s Committee for Medicinal Products for Human Use (CHMP), an entity designated to assist pharma companies in the authorization process. This was even more unexpected as PharmaMar’s drug Aplidin has found success elsewhere. The drug received the orphan drug designation in many countries and has been authorized in several staple markets including Australia, New Zealand and several Asian countries. Their most powerful competitor, Celgene (CELG), saw its drug Revlimid swiftly approved.
This is a prevalent trend in the pharma world, as big pharma companies are almost always approved, largely because they have the power to amass volumes of hard data, and are regarded as a safer bet, regardless if their drug prolongs life or not. In 2018, smaller companies such as Dexxience, Eladynos and EnCyzix all produced viable drugs that were rejected by the EMA even though were approved by the American FDA a year prior. These companies have one common thread- they are small fish in a pond of massive pharma companies and pose a market disruption threat. More direct competitors of Aplidin , namely Lenvima and Xalkori, are similar anti-cancer products that were approved with one major difference- they are backed by Eisai (ESALY) and Pfizer (PFE), global pharma leaders with average revenues exceeding an average of $29B USD.
The EU oncology sector is dominated by the Pharma giants –Roche (RHHBY), Novartis (NVS), Celgene and Aztrazenca (AZN) will constitute approximately 37% of the world market share of oncology sales by 2022, and that’s even after Roche is predicted to take a market share dive from 30.9% in 2015 to 17% in 2022. The monopoly is nearly impossible to break. Opening this market to smaller actors would mean more chances for patients to see their lives prolonged.
A European conflict of interest
The oncology pharma industry is one of most profitable, with 5 of the top 15 bestselling drugs globally. Europe alone is responsible for 24% of global oncology drug revenues, starting at $21.8 B USD. Several factors explain the large demand for anti-cancer drugs, including the increase in European cancer cases (approx. 3.7 million per year) and an ageing population set to grow in the next decade.
Amidst the high demand for life prolonging drugs, the approval hurdles are unfortunately quite persistent, with the EMA authorization process as the largest obstacle. Since 1995, the EMA adopted a centralized procedure to grant marketing access, and these are compulsory for cancer drugs. The EMA often treats approval decisions with a conservative approach, and many believe that their view of small companies and their research as seeing the glass “half full”. In fact, studies confirm that an informal approach is often required to get a drug approved – all you need to do is have a good connection with EMA committee members and your odds increase considerably.
Another challenge is price negotiation and budget allocation for patients that are in need of a better quality of life. European governments must establish reimbursement policies before the drug is launched, and it usually takes a lot longer than the standard 120 days. Out of these budgets, anticancer drugs represent less than 15% of total allocated oncology costs, and around 5% of the total drug budget. To make matters worse, the final price of cancer drugs is freely determined by the pharma companies themselves, as EU governments give them free reign. Smaller funds are actually spent on manufacturing drugs, as the final market price is solely determined by the cost of the authorization and the aforementioned research hurdles. Patients struggling for their lives end up paying for most of the cost, and the benefit of the drug is not required to be proportional to the price.
Financial Dependencies and Revolving Doors at EMA
The EMA frequently authorizes cancer drugs at around a 63% approval rate, as mostly big pharma conglomerates survive the entire process from drug target identification to patient compliance. This is not surprising, given that over 90% of the EMA’s budget in 2019 was based on fees from big Pharma players. With more resources to validate data in the application process, and paid lobbyists that can influence approval committees, an unfair advantage has derailed the playing field.
The NDA, a Swedish drug and pharma consultancy boasts an extensive lobbying agenda, as representatives have been closely involved with EMA authorization procedures. In fact, former EMA execs end up working for the firm- “six out of the 10 members of NDA’s advisory board are former regulators at EMA and other regulatory agencies”, said Anne Chailleu of Formindep, a non-profit NGO which advocates for
independency in the French health sector.
Policies have since been launched by the EMA to mitigate revolving door symptoms. Since 2016, all clinical data submitted to the EMA must be published. The agency has also taken measures to declare any conflict of interest within all committee and executive levels. For instance, Stefano Marino, EMA’s Head of Legal Department, declared himself a level 3 risk and therefore cannot participate in decision-making processes of his former employer, Sigma-Tau.
With EMA’s recent relocation to Amsterdam due to Brexit-related circumstances, the 17-month long preparations have spurred questions of how the newly minted offices would affect the agency’s data and authorization policies. Will small and big pharma players be treated equally, or will efforts to open access to other safe and effective cancer treatment for patients remain futile?