The Medicines Co. CEO Timney On Selling Inclisiran And Why Big Pharma Is Still Interested In CV Disease

Mark Timney took over the helm at The Medicines Company in December with a singular focus: wrapping up the Phase III program for inclisiran and finding a buyer for the cholesterol-lowering drug. 

The Medicines Co.'s new CEO Mark Timney took over the helm in December to execute a straightforward business plan: shepherd the RNAi therapeutic inclisiran successfully through Phase III development and find a buyer for the cholesterol lowering medicine.

"There is no doubt in my mind to really fulfill its full potential, [inclisiran] is better off in the hands of a larger pharmaceutical company," he said in an interview with Scrip. The strategy is one that is fully aligned with the company's board of directors, including Chairman Alex Denner, the activist investor who recruited him to lead the effort. Denner's investment company, Sarissa Capital Management, has a solid track record selling biotechs.

Timney was tapped as CEO of TMC in December, succeeding Clive Meanwell, who led the company for two decades. (Also see "The Medicines Co. Names Mark Timney As CEO In A Shakeup" - Scrip, 11 Dec, 2018.) The leadership change came about as TMC has shifted its business strategy over several years from a multi-product hospital specialist to a pure play drug developer focused on inclisiran. The company gained the product through a in-licensing deal with Alnylam Pharmaceuticals in 2013. (Also see "Alnylam and The Medicines Co run PCSK9 race together through $205m alliance " - Scrip, 5 Feb, 2013.)

Timney was previously CEO of Purdue Pharma, where he emphasized business development, and he previously worked at Merck & Co. as president of global primary care, where he gained extensive commercial experience in cardiovascular disease with brands like Zocor, Vytorin and Januvia.

Those two experiences have prepared him for the task at hand, he said. But executing on what appears to be the straightforward strategy could be challenging. Cardiovascular disease hasn't exactly been a hot bed of drug development at big pharma for the last decade and the first new biologics to hit the market for high cholesterol – the PCSK9 inhibitors Repatha (evolocumab) and Praluent (alirocumab) – are facing steep commercial barriers. The drugs' makers, Amgen Inc. and Sanofi/
Regeneron Pharmaceuticals Inc., respectively, have had to reset their expectations and dramatically lower the prices of the drugs since they launched in 2015.  (Also see "Sanofi/Regeneron Cut Praluent List Price As PBMs Look To Maintain Rebate Status Quo" - Scrip, 12 Feb, 2019.) It could be hard to find another large biopharma eager to wade into the PCSK9 space.

Like Repatha and Praluent, inclisiran lowers cholesterol by targeting PSCK9, but as an RNAi therapeutic, it works differently from the monoclonal antibodies. TMC believes those differences – which include dosing every six months versus every two weeks – set it apart.

Timney is convinced the persistent unmet need in cardiovascular disease is also keeping big pharma's interest piqued. Cardiovascular disease remains the leading cause of death in the US and the highest contributor to healthcare spend. He was persuaded to take the job after talking with opinion leaders and drug executives involved in the space.

"At first, I thought wow, cardiovascular medicine. That is going to be tough. It's not as easy as rare disease or oncology, but I was pleasantly surprised," he said.

"I spoke with a number of companies, some of which I knew were in the cardiovascular space and some of which I knew had been but had moved on, but it was very clear that there was still strong interest," Timney added. Among the drug makers he talked to were two currently committed to cardiovascular drugs, two that previously worked in the space and reconsidering their involvement and two companies that are involved with metabolic drugs but declared a strong interest in cardiovascular disease.

Phase III Data Readout Approaches

The big catalyst for a deal likely hinges on the Phase III data for inclisiran, which is expected in the third quarter. The Phase III program includes four pivotal trials in patients with atherosclerotic vascular disease, ASCVD-risk equivalents, heterozygous familial hypercholesterolemia (FH) and homozygous FH. Data from three of the trials is expected in the third quarter and will support a regulatory filing in the US by the end of the year. A regulatory filing in Europe is targeted for the first quarter of 2020.

In Phase II, treatment with inclisiran lowered cholesterol by more than 50% in patients with ASCVD or ASCVD risk equivalents and elevated LDL-cholesterol despite taking maximum tolerated doses of LDL-C lowering therapies.

The company recently began enrolling patients in a large cardiovascular outcomes trial that is expected to read out in 2024.

It's hard to predict the timeline for a potential sale, Timney said, pointing out that understanding the safety and efficacy of inclisiran will be important. "The timing is always dependent on each company," he said. "Do you have a gap in the pipeline? Is this the right time to fill that gap? Has something happened in the pipeline where you need to fill?"

In the meantime, TMC is keeping a close watch on the Phase III program and will begin preparing for commercialization in the case that Plan A falls through. "We will be ready if we need to to ensure that we are fully prepared to launch," Timney said.

Pricing Flexibility

The biggest challenge for the marketed PCSK9 inhibitors has been around market access, given that the biologics cost thousands of dollars a year – even as the prices have come down – when statins are available generically for a fraction of the cost. Payers have put in place a lot of paper work and red tape for patients to gain access to the drugs and they often require substantial out-of-pocket costs.

TMC sees inclisiran as having advantages in terms of cost, first because it is dosed just twice a year and secondly because the costs of manufacturing the RNAi therapeutic are cheaper than the process for biologics.

"The way that this is manufactured gives us a lot of flexibility in terms of cost of goods, so that allows us to think about pricing and the way we approach the market quite differently to what has been done in the past," Timney said. "Affordability is the approach we will take."

He said it's hard to compare the launches of Repatha and Praluent to the potential for inclisiran, which he said remains a blockbuster commercial opportunity. Repatha generated $550m in revenues in 2018 and Praluent generated $308.6m.

"Many people term [inclisiran] a PCSK9 and I think that's a little bit unfair. PCSK9 is the target but it behaves very differently than the MABs," he said. Inclisiran harnesses RNA interference to block the production of PCSK9 at its source, in the liver, and remove LDL-C from the bloodstream. "It is more like turning the tap off at its source," he added, and that's what contributes to the durable cholesterol lowering of the product.

The Phase III data read out will be a pivotal event for TMC and could determine what comes next for the company. The company has cash and equivalents of $199.7m at the end of the first quarter, enough to see it through the Phase III data read out and into 2020. After that, if inclisiran advances toward the market, TMC's timeline could fade out.