Trogarzo (ibalizumab-uiyk) became the first HIV treatment with a new mechanism of action in more than a decade to gain FDA approval. The CD4-directed post-attachment HIV-1 inhibitor, developed by Theratechnologies Inc., of Montreal, and partner Taimed Biologics Inc., of Taiwan, China, gained the nod in combination with other antiretroviral treatments (ARTs) to treat HIV-1 infection in adults with multidrug-resistant HIV-1 infection who failed an existing ART regimen.

The BLA submission was accepted June 30, 2017, with the FDA granting priority review. Approval came nearly a month in advance of the April 3 PDUFA date.

Theratechnologies priced the product, which is expected to launch within six weeks, at a wholesale acquisition cost (WAC) of $118,000 per year.

Trogarzo came with what Luc Tanguay, Theratechnologies president and CEO, called "an enviable pedigree." The drug is the first biologic – specifically, the first humanized monoclonal antibody – approved to treat HIV-1 and, as such, the first that does not require daily dosing. Infused every two weeks, Trogarzo has shown no drug-drug interactions and no cross-resistance with other ARTs – characteristics featured in its label.

The most common adverse reactions observed during its development were diarrhea, dizziness, nausea and rash, each occurring in fewer than 8 percent of patients.

"It's really a game-changer for these patients, who had pretty limited options," Tanguay told BioWorld.

The same could be said of Trogarzo's potential impact on Theratechnologies. The company's only other FDA approval came in 2010 for Egrifta (tesamorelin), an internally developed program to treat HIV-associated lipodystrophy, a metabolic complication that affects patients who take ARTs long term. (See BioWorld Today, Nov. 12, 2010.)

"We needed, as a company, to enlarge our portfolio, and having this product really changes things for us," Tanguay said.

Egrifta, which Theratechnologies markets in the U.S and Canada, brought in approximately $43 million in sales last year. The product is available on a named-patient basis in certain European markets through partners Praxis Pharmaceutical SA and AOP Orphan Pharmaceuticals AG.

Ibalizumab made a splash on both sides of the Pacific when it became the first biologic made by a Chinese company to be green-lighted by the FDA for U.S. clinical trials. R&D services giant Wuxi Pharmatech Inc. manufactured the drug, then known as TMB-355, for Taimed. (See BioWorld Today, May 8, 2014.)

The drug subsequently gained breakthrough therapy, fast track and orphan drug designations from the FDA in the HIV-1 indication. In 2016, a pivotal phase III trial showed ibalizumab helped 82.5 percent of patients who received it to meet the primary endpoint of a decrease of ≥ 0.5 log10 in viral load following a seven-day treatment period. (See BioWorld Today, March 4, 2015, and May 25, 2016.)

By that time, Theratechnologies had in-licensed commercial rights to ibalizumab in the U.S. and Canada in exchange for $1 million in cash up front and another $1 million due to Taimed at commercial launch through the issuance of 957,169 of Theratechnologies common shares (TO:TH). Theratechnologies is obligated to another $8.5 million at commercial launch, subject to certain conditions, payable as $2 million in its common shares at a price determined upon FDA approval and $1 million in its common shares at a price determined upon commercial launch, based on the volume-weighted average trading price of common shares prior to both dates, plus $5.5 million, payable in quarterly installments based on a predetermined percentage of net sales.

Taimed, which originally acquired the drug through a wholly owned subsidiary from Biogen Inc., also is in line to receive development and sales milestone payments and will manufacture and supply the drug to Theratechnologies at a transfer price of 52 percent of net sales.

Theratechnologies showed additional confidence in ibalizumab in a follow-on deal with Taimed last year for rights in the EU, Israel, Norway, Russia and Switzerland, assuming regulatory responsibilities and associated costs. Taimed retained responsibility for clinical trial activity required by the EMA and associated costs. Financial terms were similar, mainly involving an up-front payment in shares of Theratechnologies and various milestone payments. Taimed retained development and commercial rights in Asia and Africa.

Officials from Theratechnologies plan to meet with European regulators the third week of April to discuss the dossier for Trogarzo.

'Decent market opportunity'

In the meantime, the company is almost entirely focused on the U.S. launch. The approved indication addresses a U.S. patient population that Tanguay estimated at approximately 20,000 to 25,000 individuals, about half of whom no longer respond to their ART. Prior to launch, Theratechnologies plans to finalize packaging of already manufactured product before filling the supply chain, which includes distributors such as Rxcrossroads, Option Care, Walgreens Alliancerx, Accredo and Curascript. Trogarzo can be infused at home, at an infusion center or in a physician office, Tanguay said.

Theratechnologies recently quadrupled its sales team, to 43 people, and the entire team will participate in launch efforts. For now, reps are booking appointments with physicians to introduce Trogarzo, whose approval benefited from serendipitous timing during the 2018 Conference for Retroviruses and Opportunistic Infections in Boston, where the company presented poster data and met with key opinion leaders.

Theratechnologies also is working with payers to gain formulary acceptance for the drug. Treatment accessibility was "a major parameter in establishing the price of Trogarzo," Tanguay said, also citing the size of the patient population and the cost to reach and support patients and to educate physicians.

"HIV is very well known to physicians but since they previously had fewer treatment options we still have work to do," he said. "We also need to reach people where they are. We need to make sure we reach patients not just in the big cities but everywhere they live. This is the challenge we have for the next few quarters."

The partners also are mindful of continued development efforts for Trogarzo that include an intramuscular formulation that requires additional investment from both companies.

Tanguay emphasized that the WAC "does not reflect the actual net selling price," which he estimated about 30 percent lower "due to rebates to payers such as Medicaid and the AIDS Drug Assistance Program, or ADAP." Theratechnologies has instituted additional efforts to facilitate treatment access, including copay and patient assistance programs.

"Making sure that we are successful with ibalizumab in the U.S. is very important," he said.

Theratechnologies also has its eye on acquiring one or two additional niche products in the HIV space "to make sure that the sales organization is optimized," Tanguay said. "I think the sales force can manage more than two products. We're working on that as we speak."

The CEO also envisions restarting a modest development pipeline that might include one or more programs in HIV or the larger infectious disease space.

Mackie Research Capital Corp. analyst André Uddin was bullish on prospects for Trogarzo, confirming a "buy" rating for Theratechnologies shares and increasing the stock's target price to C$11.50 (US$8.91) from C$9.80 (US$7.59). With a "decent market opportunity" and a WAC "higher than our previous pricing assumption," he wrote that Trogarzo "could also be used off-label in 20K HIV patients who are intolerant to current antiretroviral treatments and 8K HIV patients that are non-adherent to conventional HIV treatments."

Shares of Theratechnologies spiked 27.7 percent Tuesday afternoon, to a one-year high of C$9.23, after approval was disclosed. On Wednesday, shares eked higher, to C$9.99, before closing at C$9.20 for a loss of C$0.03.