The cancer drug market is going through one of its most innovative and exciting times. The much lauded ‘immunotherapies’ – drugs that reveal the presence of cancer to the immune system – are significantly shifting the way in which the disease is approached. PD-1 inhibitors the likes of Keytruda and Opdivo are leading the wave of promising new immunotherapies, with both drugs blazing their way to blockbuster status at break-neck speed and both projected to be two of the best-selling drugs of all time by 2020.
But a new class of drugs capable of producing the same calibre of sales could be on the horizon.
The drugs class in question is that of the cyclin D kinase 4/6 (CDK 4/6) inhibitors.
A blistering start
Already, CDK4/6 inhibitors have shown great promise. Pfizer’s Ibrance (palbociclib) was the first of these drugs to be approved by the US Food and Drug Administration (FDA) in 2015 as a first-line combination treatment with letrozole for oestrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. The decision was made under accelerated Priority Review and Breakthrough Therapy designation programmes based on results from the PALOMA-1 trial.
Since then, in November 2016, results from the PALOMA-2 trial showed significantly longer progression-free survival in those patients given palbociclib and letrozole, compared to those given letrozole alone.
Palbociclib has performed well alongside fulvestrant too, proving superior than fulvestrant alone in terms of progression-free survival in its PALOMA-3 study. The results led to its FDA approval for this indication in February 2016.
Since its entrance into the market, Ibrance quickly reached blockbuster status. In Q4 of 2015 – not even a complete year after its launch – the drug achieved sales of $315 million.
The funds are likely to keep rolling in following Ibrance’s European approval in November. The firm are looking to launch Ibrance across Europe this year.
An expanding roster of competitors
On the back of Pfizer’s Ibrance success, other pharma companies are naturally looking to get their own piece of the action. Swiss giant Novartis’ ribociclib – believed to become Ibrance’s biggest rival in Europe – has so far replicated Ibrance’s journey, being granted FDA Breakthrough Therapy designation in August as a first-line treatment for ER+/HER2- advanced breast cancer patients, and Priority Review in the same setting in November. Since then, results from the phase 3 MONALEESA-2 have shown impressive results for the drug.
Thankfully for Novartis, the two-year head start Ibrance has experienced in the US market is likely to be significantly shortened in the European market due to its priority medicines (PRIME) adoption by the European Medicines Agency (EMA) late last year.
Another possible contender is Eli Lilly’s abemaciclib. At present, the drug is currently being investigated in two phase 3 breast cancer trials: the MONARCH 2 study investigating its effectiveness in combination with fulvestrant, and the MONARCH 3 study trialling the drug’s combination with either anatrozole or letrozole as a first-line breast cancer theraphy.
Unfortunately for Eli Lilly, both trials end this year at the end of February and June respectively. Although the company could still go down the abemaciclib as a monotherapy route, its three-year lagging behind of Ibrance will likely rule it out as a key CDK 4/6 inhibitor contender.
A lucrative future
Of course, that isn’t to say Ibrance’s first-to-market advantage means it will dominate. As the continual battle between Keytruda and Opdivo demonstrates, being a latecomer to the market by no means rules you out as a contender.
After its own blistering launch, Opdivo is struggling to keep hold of top spot as the number one PD-1 inhibitor. Since publishing disappointing trial results in August last year, MSD shares have overtaken BMS’.
Similarly, Ibrance could run into roadblocks of its own. Last week, the UK’s cost-effectiveness body NICE rejected the drug because of its high cost.
Regardless of its multiple competitors, the CDK 4/6 inhibitor class is forecast to rake in around $5 billion by 2023 across the US and parts of Europe and Asia, making up almost 50% of the breast cancer drug market. In that regard, it looks like the CDK 4/6 inhibitors could be the next big immunotherapies to look out for.