- Merck & Co. believes it has a "critically important molecule" for HIV patients in its pipeline, and is now moving the drug into Phase 3 testing based on data that showed it kept the disease in check about as well as one of the company's marketed products.
- The clinical results, unveiled Wednesday, found viral suppression was similar for HIV patients given either Merck's Delstrigo or a three-drug — and later two-drug — regimen containing the company's experimental molecule, called islatravir. The Phase 2 study evaluated three doses of islatravir in combination with doravirine, another HIV drug, and at each dose the combinations maintained antiviral activity.
- Mike Nally, Merck's chief marketing officer, last month said islatravir is poised to be a "foundational anchor" for two-drug HIV treatments. Gilead currently dominates the HIV market, supported largely by its three- and four-drug therapies, but competitors like Merck and GlaxoSmithKline are trying to make inroads with new products that have fewer active ingredients and, in theory, fewer side effects.
Islatravir represents a new class of HIV drugs that Merck argues can improve on some of the key drawbacks to existing options. The company touts how islatravir has shown high potency and a long half life, with the ability to be formulated as either an oral medication or an implantable device.
These characteristics, according to global clinical development head Roy Baynes, offer "significant forgiveness around missed doses," a primary concern for diseases like HIV where patients are often expected to take drugs daily.
"We do believe that in the pre-exposure prophylaxis, the flexible scheduling lends itself to really remarkable possibilities," Baynes said during Merck's investor day in June. "We believe it could be used as a daily dose, weekly dose, monthly dose or indeed much longer as an implantable."
An option with less frequent dosing, if proven with further testing, could spell competition for Merck's rivals.
Gilead and GSK recently launched once-daily HIV drugs they view as key growth drivers to their respective HIV businesses. In particular, Gilead's triplet Biktarvy, which combines the drugs bictegravir, emtricitabine and tenofovir alafenamide, has been a boon to the biotech's bottom line, achieving $1.2 billion in sales after less than a year on the market.
While Merck is confident in islatravir, the company is still hunting for the ideal drug with which to pair it.
At the investor event, Baynes said he had challenged his team to look into known HIV drug classes and find new molecules that would be more compatible with islatravir. Early research has already found potential drugs with "more favorable kinetics" than doravirine, according to Baynes, though the initial Phase 3 test will be in combination with doravirine.
"Hopefully, the clinical data will support the preclinical data and we will have a combination that we can dose once weekly," Daria Hazuda, vice president of infectious diseases discovery, said at the event.
"That's our real goal in the treatment space, is to find a partner that will allow us to have an effective combination that can be dosed once weekly, as well as a partner that could be co-administered in an implant for a duration of six months or more."
Such a drug could give Merck's HIV portfolio a needed boost. Sales of its main HIV product Isentress (raltegravir) dipped 5% last year and 13% the year before due to increased competition in the U.S. and Europe.
Merck did, however, secure two HIV drug approvals in the U.S. last year: one for Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate) and one for Pifeltro (doravirine).
In the study behind Wednesday's data announcement, Merck tested 0.25 mg, 0.75 mg and 2.25 mg of islatravir. For the first 24 weeks, patients received either one of those doses plus doravirine and lamivudine (another antiviral), or Delstrigo. Once that part of the study completed, patients in the experimental arms were switched onto just islatravir and doravirine for the next 24 weeks.
After nearly a year, the portion of patients who were virologically suppressed were 90%, 90%, 77% and 84%, respectively, for the 0.25 mg, 0.75 mg, 2.25 mg and Delstrigo groups. Six patients across the islatravir treatment groups experienced virologic failure, compared to one patient in the Delstrigo group.