Oncology round-up: Shareholders question BMS/Celgene merger, while Merck & Co’s Keytruda keeps getting stronger

Will it happen or not? There are doubts about whether the proposed $74 billion merger of cancer drug firms Bristol-Myers Squibb and Celgene can go ahead after two BMS shareholders came out strongly against the deal.

Hedge fund Starboard Value has opposed the deal, along with another investor, Welling Management.

Starboard’s assessment of the deal in a letter to shareholders was particularly scathing, saying that it would mean BMS becoming saddled with Celgene’s considerable patent cliff.

The merged company will rely on drugs approved from an “extremely risky” pipeline to produce enough revenues to cover the loss of patent protection on Revlimid –  Celgene’s ageing blood cancer blockbuster that brings in annual sales of around $9.5 billion.

Starboard said BMS would be better off as a stand-alone company, or finding a buyer to get the best value from its shares.

BMS said that buying Celgene is a “natural next step” in its strategy and will create a “leading biopharma with increased scale”.

Celgene’s pipeline has more than $15 billion in total revenue potential, BMS said, and the merged company will have a portfolio including more drugs that are early in their lifecycle, with several years of premium pricing ahead of them.

The enormous cash flow of around $45 billion will enable the merged company to quickly pay off its debts, BMS added.

Keytruda powers ahead

The BMS merger is being considered in no small part because of the success of arch rival in immuno-oncology, Merck & Co’s Keytruda (pembrolizumab), which like BMS’s Opdivo is an anti-PD1 checkpoint inhibitor.

Keytruda is now ahead in sales after getting approved in first-line lung cancer – a lucrative indication where Opdivo has failed to produce convincing results.

Analysts are predicting that a combination of Keytruda and Pfizer’s Inlyta will become the standard of care in renal cell carcinoma (RCC) thanks to impressive trial results and a price advantage over BMS’ rival drug.

The combination of anti-PD-1 therapy Keytruda with tyrosine kinase inhibitor Inlyta (axitinib) reduced risk of death in RCC by around 47%, compared with Pfizer’s established cancer drug Sutent (sunitinib), in the phase 3 KEYNOTE-426 study – announced at the 2019 Genitourinary Cancers Symposium (ASCO GU).

The treatment also increased 12 month overall survival by 11.6% and overall response rate by 23.6%, as well as boosting progression free survival by four months compared to Sutent.

Results were consistent across all risk groups, and regardless of expression of the biomarker PD-L1.

The results will help Keytruda take a further bite out of its arch rival, Bristol-Myers Squibb’s Opdivo, which is already approved in combination with the company’s Yervoy (ipilimumab) for advanced renal cell carcinoma, but had demonstrated lower rates of progression-free survival.

The combo has already bagged priority review from the FDA.

Keytruda also looks likely to get a patient-friendly six week dosing schedule in Europe, after a recommendation for a label change from the CHMP scientific committee that will be passed on to the European Commission for approval in the coming weeks.

CAR-T developments

March has already been a busy month in the field of CAR-T therapy, with Gilead expanding a partnership with MaxCyte, and Precision BioSciences filing for a $100 million IPO for its ‘off-the-shelf’ cancer cell therapies.

Gilead’s subsidiary Kite Pharma has revised a deal with London-listed MaxCyte to apply its transfection technology to up to 10 targets.

MaxCyte engineers its CAR-T (chimeric antigen receptor T-cell) therapies without using viruses, unlike many of its rivals and the two already approved treatments in this class.

The company has developed a technology that uses an electrical field to reverse the permeability of cell membranes.

This means that molecules, such as the human messenger RNA used in-house by MaxCyte, can pass into the cell and modify its internal workings without using viruses or chemicals.

The idea is to shorten or simplify the production process, and reduce costs – something that is proving to be a major problem for the CAR-Ts approved so far.

In a separate development, Precision BioSciences is aiming to raise up to $100m in an IPO to develop ‘off-the-shelf’, or allogeneic CAR-T therapies.

Precision raised $110 million in Series B funding a few months ago and said it needs the cash to complete a phase 1/2a trial of a CAR-T for non-Hodgkin’s lymphoma due to start in the coming months.

Like the already-approved CAR-Ts from Gilead and Novartis, the therapy codenamed PBCAR0191 targets the CD19 receptor.

But because it is manufactured from a bank of cells from healthy donors it should be faster and cheaper to make than autologous CAR-Ts produced from a patient’s own cells.

Bayer files prostate cancer drug in Japan

Bayer has filed its prostate cancer drug darolutamide with Japanese regulators, in an attempt to ratchet up the pressure on rivals Johnson & Johnson and Pfizer/Astellas.

With darolutamide, developed in partnership with Finland’s Orion Corporation, Bayer is hoping to take market share from J&J’s Erleada (apalutamide) and Pfizer/Astellas’ Xtandi (enzalutamide), which have become standard therapies at several different stages of the disease.

Bayer has already filed darolutamide with the FDA, and has followed this up with a filing in Japan in castration-resistant prostate cancer.

The German pharma has also filed the drug with the European Medicines Agency (EMA).

Bayer and Orion think that their drug may have a safety advantage over their rivals and is tipped to break through the billion-euro annual sales barrier if approved.

However, while analysts think that the side effect profile is favourable based on trial data so far, efficacy is comparable and this may not be enough to win over prescribers looking for an improvement on established therapies.

The filing is based on data from the phase 3 ARAMIS trial in men with non-metastatic disease, which showed a statistically significant improvement in metastasis-free survival for darolutamide plus androgen deprivation therapy (ADT).

In Aramis, 1,509 patients were randomised in a 2:1 ratio to receive 600 mg of darolutamide twice a day or placebo along with ADT.

Bayer is also developing darolutamide in metastatic hormone-sensitive prostate cancer, where the phase 3 prostate cancer trial ARASENS is testing its safety and efficacy.