Memorandum

Amgen 2Q14 – PCSK 9 inhibitor evolocumab to be submitted in the US and Europe in 3Q14 – July 30, 2014

Executive Highlights

  • Amgen announced in its 2Q14 report plans to submit its phase 3 PCSK9 inhibitor evolocumab (AMG 145) in the US and Europe in 3Q14; the submission will include the SureClick autoinjector device and not the mini-doser device.
  • Management outlined first steps of the company’s restructuring plan to “reallocate resources”, which includes significantly reducing Amgen’s workforce and closing down sites.

Amgen reported 2Q14 financial results yesterday afternoon in a call led by CEO Mr. Bob Bradway. The company’s most exciting therapy in development for cardiometabolic disease is evolocumab (phase 3), an injectable PCSK9 inhibitor compound in development that shows great promise for LDL cholesterol lowering. Below, we include our top five highlights from the quarter, followed by a selection from Q&A.

Top Five Highlights

1. Amgen now plans to submit evolocumab (AMG 145) in the US and Europe in 3Q14. It has been notable to see how aggressively Amgen has advanced the planned timeline for evolocumab’s submission – following a previously announced delay for the US filing, Amgen announced in 1Q14 that the company was back on track for global filing in 2014. Amgen plans to file both once-monthly and twice-monthly dosing options for the injectable drug.

  • Evolocumab is on track to be the first PCSK9 inhibitor to be submitted to regulatory authorities for approval. Its most late-stage competitor is Sanofi’s alirocumab, but Sanofi is slightly behind with plans to file by the end of the year – the company very recently reported new phase 3 data on alirocumab. Other competitors include Pfizer’s bococizumab, which is enrolling patients in phase 3 trials, Lilly’s phase 2 LY3015014 (which might be dosed less frequently than evolocumab), and Catabasis’ CAT-2003 (in phase 2) and CAT-2054 (preclinical). BMS had previously listed a PCSK9 adnectin as of June 2013, but it no longer appears in the company’s pipeline – this is unsurprising since it left diabetes and presumably related areas in late 2013. Similarly, Roche’s phase 2 RG7652 was recently discontinued.

2. We learned during prepared remarks that Amgen will not include its automated mini-doser device in the initial submission in order to maximize the probability of a first cycle approval. The mini-doser is a pager-sized device that administers the entire monthly dose as a single infusion, as opposed to the more standard SureClick autoinjector (the delivery device to be used for the initial filing) for which Amgen has years of exposure data. Advantages of the mini-doser include a more gradual infusion, minimal patient involvement, and no visible needle penetration. Management noted that Amgen wishes to avoid the risk of delaying the entire drug submission by including the mini-doser. Instead, Amgen plans to submit a device supplement for the mini-doser shortly after approval. As management astutely noted, this means that the device will be evaluated on a device review schedule, rather than the more lengthy drug review schedule.

  • As diabetes medications increasingly move from once or twice-daily options to once-weekly alternatives, we wonder whether we could see a “mini-doser” or similar device for diabetes. In the once weekly GLP-1 agonist field, we are already seeing new and innovative ways to improve the patient experience, such as Lilly’s auto-injector “single-use pen” for dulaglutide. Better devices can most certainly have a major impact on the patient experience (and therefore adherence)

3. Results from Amgen’s phase 3 trials program for PCSK9 inhibitor evolocumab have been impressive – the first of that data was presented at the 2014 American College of Cardiology conference, and demonstrated mean LDL reductions of ~50-75% in a wide range of patients (with statins, in statin-intolerant populations, patients with familial hypercholesterolemia). At least so far, there have not been any major safety or tolerability issues observed.  

  • FOURIER, evolocumab’s CV outcomes trial (estimated primary completion date of December 2017; ClinicalTrials.gov Identifier: NCT01764633) is currently recruiting participants. The results of this study will garner significant attention as they will help contribute to the debate over whether LDL-lowering alone has CV benefits. If evolocumab in fact reduces CV events, the PCSK9 inhibitor class would move into an extremely important role, joining statins in the select group of drugs capable of reducing hard CV events. During Pfizer’s 2Q14 call, management noted that outcomes data on this class (or differences in outcomes data between the class) will be key in determining success with payers.

4. Amgen has only one diabetes candidate in its pipeline, AMG 876, which is an undisclosed fusion protein (potentially an FGF-21 analog), on which there was no new updates in the call. For context, AMG 876 has been in phase 1 for at least two years. In February 2013, Amgen terminated its initial single-ascending dose study for AMG 876 and its multiple ascending dose study is in phase 1 and currently recruiting participants (ClinicalTrials.gov Identifier: NCT01856881).

5. Amgen management announced that it is reducing its workforce (currently ~20,000) by between 2,400 and 2,900 positions beginning in 4Q14 and through 2015. The restructuring aims to streamline the organization, reduce layers of management, increase managerial spans of responsibility, as well as implement a revised geographic site plan (closing Washington and Colorado manufacturing and R&D facilities by end of 2015). Management stated that next steps as well as more information on the pipeline and commercial plans will be discussed at Amgen’s business review meeting to be held in 4Q14. Amgen’s early-stage diabetes pipeline does not feature many candidates, and this news does not make it seem likely that we will see a number of new early-stage candidates from them soon.  

Questions and Answers

Q: I was just wondering if there are any new pieces of clinical data that you're expecting that might change the level of reinvestment either up or down that you've cited in your restructuring?

A: The reception to our evolocumab data has been very positive. We look forward to continuing to advance that candidate and to begin investing in the kinds of activities that would be typical before the launch of such a medicine.

Q: On evolocumab, what was the reasoning behind the decision to sort of split up the two formulations?

A: So this is not a formulation issue – the formulation is the formulation that's going be registered along with the every two-week and every month dosing data. The SureClick autoinjector, which we have many, many years of patient years of exposure and with which regulators are very familiar, will also be registered. What we are not initially registering is the automated mini-doser device, which administers the entire volume necessary for monthly injection as a single infusion. And the reason for that is to not take a chance, given the novelty of that device as compared to our autoinjector, of delaying the entire drug submission by including that. Rather, we plan to instead get the autoinjector approved, get the product ready for launch, and then submit the device shortly after approval, which will be reviewed on a device clock, not a drug review clock.

Q: What can you tell us about the pace of commercial investments in evolocumab, just especially given the earlier filing?

A: We've filed now for ivabradine, the drug for cardiac heart failure. Obviously it'll be the critical path to Amgen moving into the cardiovascular space. Clearly that drug will be potentially approved sometime early next year, and we're setting up the commercial launch to ready ourselves for that. That team of specialists plus the medical organization will be the same organization that then takes evolocumab to market a bit later during 2015.

Q: Can you talk about what additional commercial infrastructure that you think you will need in order to launch evolocumab and other products?

A: We are looking at putting together a definitive cardiovascular team and that team will evolve over time as we then go from ivabradine to evolocumab. The other products we'll be launching fall pretty much within our existing organization in terms of the oncology skills. That's about as much language we would want to disclose at this point in time.

 

-- by Melissa An, Manu Venkat, and Kelly Close