Last Thursday, I attended the Roche Investor meeting in Wall Street, live-tweeted it using the hashtag #RocheIR and enjoyed an interesting event packed full with lots of information to digest.  

Photo-6Luckily, I bumped into an old colleague from Sandoz UK days and was delighted to learn that he is now Global Head of Regulatory at Roche.  Of course, if you spend a day out of the office, you pay for it severely the next day with an even bigger pile of emails, client requests, RFPs and telecons to catch up on >.<

In fact, I was so busy, I didn't have time to post a blog about Thursdays event on Friday, but I did manage to interview Dr. Laura Esserman, the breast cancer surgeon at UCSF behind the fascinating I-SPY2 project that we discussed last week. More on that tomorrow.

The next two days of blogs will cover two reports on the Roche pipeline (non-oncology and oncology) and Dr. Esserman's unique perspective on getting the I-SPY2 project up and running, she has certainly made a difference shaking things up and challenging people's approach to drug development in a short space of time. 

Let's begin with the non-oncology agents in Roche's pipeline.

Granted I normally write more about oncology, hematology and immunology here, but my background in Pharma started in more humble beginnings as a sales rep in the statin market, where we were also looking to differentiate ourselves by being an attractive option for people with diabetes, who have a much higher risk from long term CV mortality.  

I was therefore very interested to see where Roche were going with this approach fifteen years later because we never had much success with it, despite Marketing thinking it looked to be an attractive opportunity no one was exploring.  However, the undoubted long risk of earlier mortality and morbidity is subsumed to more urgent and immediate needs such as getting sugar levels under control and insulin levels regulated.  Adding yet another drug into the mix complicates things for physicians considerably. Plus taking oral drugs over time also results in long term compliance issues, which may impact outcomes negatively.

Dalcetrapib is being developed for dyslipidemia and cardiovascular high risk patients. The first trial looks at artherosclerotic disease progression, lipid profile and biomarker profile and long-term safety profile of dalcetrapib in people with established coronary artery disease compared to placebo. 

The primary endpoints include:

  • Nominal change from baseline to study end in coronary percent atheroma volume (PAV) of the target coronary artery assessed by IVUS.
  • Rate of change from baseline to study end in carotid intima-media thickness (CIMT) using B-mode ultrasound

The second trial is looking at the potential of dalcetrapib to reduce cardiovascular morbidity and mortality in stable coronary heart disease patients with recent Acute Coronary Syndrome (ACS) and evaluate the long term safety profile of the drug, again, compared to placebo. 

The primary endpoint is defined as:

  • Time to first occurrence of any component of the composite cardiovascular event (cardiovascular mortality and morbidity)

These two phase III trials are currently recruiting people with coronary artery disease, so we won't know the results for quite a while, probably over the next 2-3 years.  Such large scale trials are very expensive and time consuming to conduct.  For all the the noise about statins reducing cholesterol, I sometimes wonder what impact they actually have on long term mortality and morbidity. Do they lead to any meaningful clinical change in outcomes, ie improved survival, rather than just lowering cholesterol per se?

Roche also have two drugs in development for type II diabetes, both of which are tongue twisters: taspoglutide, a new GLP-1 drug for Type 2 diabetes, and aleglitazar, for cardiovascular high risk in diabetes. The diabetes market is suddenly getting very crowded with numerous insulin, syringes, pens, pumps, and oral therapies all available. 

Thus as a marketer, I'm wondering how new products into these segments differentiate themselves from existing therapies in this competitive disease?  It's one thing to claim blockbuster potential, but quite another to capture the heart and minds of the physicians prescribing yet another me-too in a crowded existing market segment.  

The $64M blockbuster question in diabetes for BMS's Onglyza, in the DPP-4 segment, rapidly turned into a spectacular $4M flop in the launch year. The inhaled insulins such as those from Pfizer and Mannkind were either withdrawn or struggle to make it to market. Two precautionary tales of humility in the diabetes market if there ever were some.

How Roche develop and differentiate taspoglutide and aleglitazar from existing segment leaders will therefore be an interesting process to watch.  For now, we can sit back and wait for the various clinical trials to complete and see how the agents stack up.  The phase III trials were initiated for aleglitazar were initiated in 1Q10, taspoglutide initial phase III results were released in 4Q09 and further results are expected in 2010. The results for dalcetrapib will not be available for a few years given the enrollment is just starting.

Two other non-oncology drugs in development include RG1678, a GLY-T1 inhibitor, for treatment of the negative symptoms of schizophrenia. The initial phase II results were positive last year and phase III trials are planned for 2010.  

Ocrelizumab is a humanised CD20 monoclonal antibody similar to rituximab. The phase III trials were negative in rheumatoid arthritis and lupus, despite the agent being developed to reduce the development of drug neutralizing antibodies and infusion reactions. Recent studies, however, established that the safety risk associated with ocrelizumab outweighed the benefits and Roche disclosed that several patients died from infections so the development in RA and lupus was promptly suspended. Meanwhile, ocrelizumab is also being developed for the treatment of people with multiple sclerosis and a Go/No Go decision for the phase III development is expected this year.

Given the focus on five main disease areas including oncology, virology, immunology, metabolism and CNS, it is good to see new agents being developed in the metabolism and CNS areas after the long term focus on oncology with Genentech lately.  How well they will do in the long run compared to the oncology pipeline, only time will tell.