- The Medicines Co. plans to quickly move forward with late-stage development of its PCSK9 synthesis inhibitor, bolstered by new study results it believes will differentiate the high cholesterol treatment from existing PCSK9 drugs already on the market.
- Interim data from the company's Phase 2 trial, presented Tuesday at a meeting of the American Heart Association, showed a single 300 mg injection of inclisiran reduced LDL-C, or "bad" cholesterol, by an average of 45% through 90 days.
- The Medicines Co. has trimmed its pipeline to free up funding for development of inclisiran, halting further development of its experimental heart drug MDCO-216 earlier this month.
While final follow-up data is still forthcoming, the results announced Tuesday gave The Medicines Co. enough evidence to green light a 300 mg injection as the optimal dose moving forward.
Among the nearly 500 patients with 90 days of follow-up, treatment with a single 300 mg subcutaneous injection led to an average LDL-C reduction of 51% through two months and 45% through 90 days — comparable efficacy to Amgen's Repatha (evolocumab) and Sanofi/Regeneron's Praluent (alirocumab).
Another cohort of 189 patients who had been followed for 180 days post-treatment saw a similar 43% reduction in LDL-C levels at the end of the period, suggesting inclisiran's effect was durable.
A Phase 3 study is in the works and the company believes the data support biannual or triannual dosing, which would be a significantly more convenient treatment regimen than either Repatha or Praluent.
Notably, treatment with inclisiran did not lead to a higher incidence of adverse events compared to placebo. Due to the less frequent dosing of inclisiran, follow-up safety data across multiple doses will be an important area to watch.
Company CEO Clive Meanwell, speaking at a panel presentation Tuesday, expressed confidence in The Medicines Co.'s ability to carry out late-stage development of inclisiran, noting the biopharma had "shifted capital deployment strategies in anticipation of this moment."
The company ended the third quarter with just over $600 million in cash and equivalents on hand, an amount Meanwell said was "more than enough" to bring inclisiran to market.
Pfizer's decision to ax its PCSK9 drug bococizumab, coupled with inclisiran's strong showing in Phase 2, could give The Medicines Co. a real opportunity to compete in the cholesterol-lowering market.
Yet, PCSK9 drugs have not been the slam-dunk some expected. Repatha and Praluent have struggled to gain traction on the market, and payers have been reluctant to cover the pricey drugs. The Medicines Co. still needs to carry out its Phase 3 study and likely will need to complete a cardiovascular outcomes trial as well, putting any approval several years down the road.
So far, the company's strategy to clear the decks in favor of inclisiran has notched an early win. But it remains a bet dependent on a more favorable market than currently seen.
Another thing that could get in the way for the drug is the science; part of the pushback to currently marketed therapies has been the lack of understanding into the role that LDL-C plays. Scientists are still debating about whether lowering bad cholesterol will ultimately lead to better cardiovascular outcomes. Data from large outcomes studies over the next two years could bring the market more definitive answers.