Cubist: Meeting the challenge in antibiotics

Cubist's Patrick Vink on the need for new antibiotic treatments

A few years ago European Antibiotic Awareness Day, which took place on November 18 to highlight the growing threat of resistance to antibiotic treatments for infectious diseases, would have passed most people by with barely a thought, satisfied with the current number of available drugs and their effectiveness.

This year though the day stood as evidence of the growing awareness among the public, governments and healthcare community that antimicrobial resistance is a deadly serious public health threat that doesn't show any sign of abating.

Among those adding their voice to the growing chorus demanding new antibiotics and more sensible use of existing treatments was Vytenis Andriukaitis, the newly-elected European Commissioner for Health and Food Safety.

“The near doubling of resistance in a certain bacteria in three years is truly alarming, and illustrates the need to tackle the issue from all directions,” he said.

“Antimicrobial resistance is one the most pressing public health issues of our time, and as incoming health commissioner, I pledge to prioritise it throughout my five-year mandate.”

Other organisations proposing actions to stem the impact of antimicrobial resistance include the World Health Organization (WHO), which is in the middle of developing a global action plan to tackle what it describes as “one of the three greatest threats to human health”.

The plan will likely cover much ground, including raising awareness of the consequences of imprudent use of antibiotics, but another key area will be the development of new antibiotic drugs.

Antibiotics used to be big business for pharma, with 16 drugs approved by the FDA in the period 1983-87 and 14 approved in 1988-92. However, the number of approvals for new antibiotics has shrunk in recent years, with just five approved by the FDA during 2003-07 and two approved in 2008-2012.

This is due to a variety of reasons, including hubris on the part of the healthcare community and the poor return on investment offered by new treatments due to their short-term use causing large pharma companies to divert attention to more profitable areas, such as the long-term conditions diabetes and cancer.

Cubist expansion

One company that has remained in the field despite these difficulties is US-based Cubist Pharmaceuticals, which has been involved in developing new antibiotic treatments since 1992 and recently expanded its efforts with the creation of an international base in Switzerland and a $400m investment in R&D.

Cubist's strong pipeline has attracted the attention of Merck & Co, which announced in December 2014 that it has agreed to acquire Cubist for $8.4bn, boosting its own ambitions in antibiotics.

One of the key figures in turning Cubist into such a strong target is Patrick Vink, who joined Cubist in 2012 as senior VP and general manager of international business and is set to become chief operating officer in the New Year.

Cubicin (daptomycin) is Cubist's leading product with net revenues of $256.7m for the third quarter of 2014

Speaking to PME at the launch of Cubist's Swiss office in October - before the agreement with Merck & Co - Vink explained why Cubist has remained active in antibiotic development when other companies have shied away.

“We stayed in this market because we saw the unmet need. We knew there were patients out there who needed these new products and that no alternative options were forthcoming.”

The optimism of Cubist has been justified many times over and is being seen in wider efforts to spur development of new drugs. This includes the introduction of the FDA's Qualified Infectious Disease Product (QIDP) classification to create a more favourable regulatory environment for antibiotic products, while the UK has launched a review into how the research environment can be improved.

For Cubist its beliefs have been justified with the approval of the new antibiotic Sivextro (tedizolid phosphate) to treat acute bacterial skin and skin structure infections, while another drug - ceftolozane/tazobactam - is on course for approval in both the US and Europe.

These developments are a welcome addition for Cubist, according to Vink who says that there is now an awareness that antimicrobial resistance is a “real problem”.

“We are embracing the fact that initiatives like the one launched by UK Prime Minister David Cameron are actually here,” he said. “And the QIDP, as part of Generating Antibiotics Incentives Now Act (GAIN Act), is a good signal that in the US we need incentives to advance in this area and the unmet need in antibiotics is being taken seriously.”

And there is now no denying that resistance to antibiotics is a very serious issue, said Vink, who explained why bacteria pose such a big problem.

“They are organisms that are pretty smart in beating the current therapeutic options. They are a continually moving target and we are in continuous need of new products.

“We estimate that more than 30,000 people per year die in Europe alone due to bacterial infections and hospital-acquired infections are in particular a problem because that is where resistance usually occurs.”

Cubist's pipeline

It's not just the current threat but its growth that worries Vink, who explains that this is what Cubist is ultimately combating.

“We are in desperate need of new anti-infectives. Only a few products have been developed and launched in the past few years. Everyone recognises we need more - not only us, as a leading member of the pharma community working in the area, but also governments and global health organisations.”

This need to grow is part of the reason why Cubist chose to set up shop in Zurich, adding to its existing corporate headquarters in Lexington, Massachusetts.

“AMR is something that is increasing and it doesn't stop at borders - we see big resistance problems in Europe. Our first product was commercialised in Europe by another company but we felt now that with our pipeline and global reach it was the right time to start doing it ourselves.”

Patrick Vink

A European base will also help Cubist build relationships with partners in the region, which include members of the Innovative Medicines Initiative (IMI) - a public-private partnership bringing together pharma companies and the European Commission.

“We are a member of trade body the European Federation of Pharmaceutical Industries and Associations (EFPIA) and as part of that membership we are actively involved in the IMI's efforts in AMR,” said Vink.

“There are a number of collaborations we have with biotech companies in Europe, but regarding the IMI collaboration, it is too early yet for discussion.”

Several other companies are signed up to the IMI's efforts in AMR, including GlaxoSmithKline, AstraZeneca, Janssen and Sanofi, suggesting that the larger firms are coming back to antibiotic development.

GSK has even been working with the US government in AMR research, while AstraZeneca is a step ahead having had the antibiotic AZD0914 receive fast track status from the US FDA for use in gonorrhoea.

Patient benefit

For Vink this renewed interest in the area can only be a good thing for patients. “It's good that companies are coming back into this fray. But I would say it's still a company like Cubist that is dedicated to this area that will make a difference.”

Despite the urgent need for treatments, return on investment remains a key issue and the right incentives are a necessity if companies are to commit to the development of new antibiotics. This boils down to three core areas outlined by Vink.

“First we need to have a comprehensive framework for regulatory requirements that are adapted to specific needs of AMRs,” said Vink. “This includes pathogen specific pathways.

“Furthermore what really helped in the US was the extension of the exclusivity period as drugs don't always have fast uptake in terms of utilisation but grow over time.

“The third thing is that antibiotics, which are one-time use but save lives, require a premium price to justify investment. They are not treatments for chronic diseases where once a patient is on a product they are on it for a long time.

“We need the right incentives, the right regulatory frameworks and extension of exclusivity.”

It seems that more and more healthcare stakeholders are coming to Vink's side on this matter, and that real changes are being implemented by governments and health bodies to both raise awareness of the danger of AMR and that a more favourable R&D and regulatory environment is a required to ensure new drugs hit the market before it's too late.

And for Vink the real winner will be the people that gain another weapon to fight infections: “It is an exciting time for patients as we bring more products to market that are needed.

“We are very eager to work in an alliance with medical care providers, payers, regulators and governments to bring these products to market for the benefit of patients.”