Cabozantinib (s)-Malate

The two phase 3 successes Merck reported Tuesday should “inspire investor confidence” in the company “post-Keytruda,” analysts at Leerink Partners wrote in a note to clients. As Merck looks for growth opportunities ahead of Keytruda’s tumble over the patent cliff, the company’s future now looks a bit brighter in the glow of two late-stage trial wins for cancer drug Welireg.In fact, one of those readouts could see Welireg inherit a large portion of the renal oncology market that’s currently dominated by Merck’s aging PD-1/L1 megablockbuster, one group of analysts predicts.The two phase 3 successes Merck reported Tuesday—covering Welireg with Keytruda in post-surgery clear cell renal cell carcinoma (RCC) and Welireg plus Eisai’s Lenvima in advanced RCC patients whose disease progressed after PD-1/L1 treatment—should “inspire investor confidence” in the company “post-Keytruda,” Daina Graybosch’s team at Leerink Partners wrote in a note to clients.The analysts were particularly enthusiastic about the Welireg-Keytruda combination, which they predicted could become a “substantial revenue contributor” for Merck if approved. However, the second set of results on the Welireg-Lenvima cocktail is “less clearly positive,” the Leerink team admitted.Merck did not divulge detailed results from the pair of late-stage studies, which are coded LITESPARK-022 for the Keytruda combo and LITESPARK-011 for Welireg-Lenvima. The company will share more data at upcoming medical meetings and plans to furnish global regulators with the latest results on the RCC combo candidates, Merck said.In patients with clear cell RCC who’d had a kidney removed, Welireg with Keytruda charted a “statistically significant and clinically meaningful improvement” in disease-free survival versus Keytruda alone, satisfying LITESPARK-022’s primary endpoint, Merck said in an Oct. 28 press release. The New Jersey pharma giant said it will continue to assess overall survival (OS)—which forms a key secondary endpoint—in the study.As for Welireg plus Lenvima, the combination helped the LITESPARK-011 trial meet “one of its primary endpoints of progression-free survival (PFS)” in advanced RCC patients who’d failed PD-1/L1 therapy, demonstrating—again—a “statistically significant and clinically meaningful improvement” in PFS over Exelixis’ Cabometyx, according to the company.While a trend toward improvement in OS—LITESPARK-011’s second primary endpoint—was observed, the result hadn’t reached statistical significance at the time of an interim analysis, Merck noted in a separate press release.Investors may be failing to appreciate the opportunity of Merck’s Welireg-Keytruda cocktail in the adjuvant clear cell RCC market, the Leerink analysts wrote in their note. They figure a combination approval in clear cell RCC would help Welireg “inherit the large market currently served exclusively by [Keytruda]” and could raise Merck’s annual U.S. revenue opportunity in the indication from $2.3 billion to $6.3 billion, and then $5.4 billion in 2029 after Keytruda loses market exclusivity.Graybosch’s team added that a victory in LITESPARK-022 was “not guaranteed,” pointing to the tough comparison to Keytruda as the study’s control drug.The situation with Welireg and Lenvima in LITESPARK-011 is far less clear-cut, the analysts noted.Missing OS endpoint will likely be a crucial piece of information for doctors treating kidney cancer patients, given the greater potential for toxicity through Lenvima’s inclusion in the experimental combo treatment compared to Cabometyx monotherapy, the Leerink team explained.Nevertheless, the fine details from the trial will be the deciding factor in Welireg-Lenvima’s potential success, the analysts caveated, singling out Merck’s future release of detailed LITESPARK-011 data as an “important catalyst” for Merck and its competitors in the space. The trials represent part of Merck’s overall ambition to maintain its growth momentum through the Keytruda loss of exclusivity, which is expected later this decade. Welireg, acquired by Merck in its acquisition of Peloton, won its initial FDA approval back in 2021 to treat certain tumors in patients with von Hippel-Lindau disease. In 2023 and 2025, the drug added indications in kidney cancer and as a treatment for rare neuroendocrine tumors, respectively. Outside of oncology, another key growth driver for Merck is Winrevair, a blockbuster-to-be that’s been making progress with its launch in pulmonary arterial hypertension since its original FDA approval last year. Besides those two medicines, the company this year made a sizable M&A play for Verona Pharma, striking a $10 billion buyout that closed just this month. With that deal, Merck added Ohtuvayre, a first-in-class drug for chronic obstructive pulmonary disease that also gained its original FDA nod last year. During a July earnings conference call to discuss the Verona deal, Merck CEO Robert Davis touted the company’s expectation to “benefit from approximately 20 additional new growth drivers in the coming years, almost all of which have blockbuster potential.”  For now, though, Keytruda remains the company’s bread and butter, generating $29.5 billion last year. In recent quarters, the medicine has been responsible for roughly half of Merck’s overall revenue haul. Merck’s efforts to prepare for the drug’s loss of exclusivity haven’t only centered on adding new growth drivers to the mix. The New Jersey pharma giant recently launched a sweeping cost-cutting campaign designed to save $3 billion per year by the end of 2027. Under that program, Merck plans to cut about 6,000 jobs. 

Plus, news about Cybin, Incyte, Roche, Merck, Eisai, Neuphoria Therapeutics, Aldeyra Therapeutics and X4 Pharmaceuticals: 🏭 FDA issues CRL to Regeneron: The drugmaker has officially been handed a complete response letter for its pre-filled syringe for Eylea HD. The company had warned in August that it expected regulatory delays after issues were found at a Catalent site in Bloomington, IN, that’s now owned by Novo Nordisk. The plant has since been issued an “official action indicated” classification. Another customer of the Indiana site, Scholar Rock, also received a CRL related to the plant. — Anna Brown 🧪 AbbVie scraps asset licensed from Dragonfly Therapeutics: The Chicago-area pharma giant terminated a Phase 1 test of the first asset that it licensed from Dragonfly . AbbVie started testing ABBV-303/DF4101 in 2024 in solid tumors. Dragonfly CEO Bill Haney told Endpoints News that the company’s other programs with AbbVie are ongoing. Dragonfly has multiple internal candidates in clinical testing as well as Phase 1 programs with Bristol Myers Squibb and Merck. It also has a preclinical pact with Gilead. — Kyle LaHucik 💵 Cybin’s $175M direct offering: The company is selling about 22.3 million shares at $6.51 apiece from several blue-chip investors, including Venrock Healthcare Capital Partners, OrbiMed and Point72. It’s developing a psychedelic called CYB003 as a treatment for major depressive disorder. — Jaimy Lee 🛠️ Incyte halts work on two drugs: Under new CEO Bill Meury, the drugmaker has paused development of its anti-CD122 candidate, called INCA034460, and its BET inhibitor, called INCB57643. The biotech also ended povorcitinib’s development in chronic spontaneous urticaria and hinted that more pipeline adjustments are in the works. “We are taking a deliberate approach to pipeline prioritization. We are actively reviewing our R&D efforts and focusing on high-value programs that are scientifically differentiated, address unmet medical needs, and have the potential to significantly drive Incyte’s next phase of growth,” Meury said in a release.  Incyte also raised its revenue guidance for the year. It’s now in the range of $4.23 billion to $4.32 billion. — Kyle LaHucik 🔬 Roche’s Gazyva succeeds in kidney disorder: The drug met its primary endpoint in a Phase 3 study for idiopathic nephrotic syndrome, a rare autoimmune disease that affects the kidneys. Roche will head to the FDA to discuss next steps for the drug, but the timing is not yet clear. Gazyva was approved earlier this month for the treatment of active lupus nephritis. — Max Gelman 💊 Merck, Eisai tout kidney cancer data: The combination of Merck’s Welireg and Eisai’s Lenvima achieved a statistically significant improvement in progression-free survival over Exelixis’ Cabometyx in advanced renal cell carcinoma. Overall survival did not reach statistical significance, though Merck and Eisai noted this was an interim analysis. There was also a “trend toward improvement” on OS. — Max Gelman 📈 Neuphoria Therapeutics adopts poison pill after Phase 3 fail: The biotech’s board selected the shareholder rights plan to “protect the interest of the company and its stockholders.” The move lowers the chances that a person or group will accumulate enough shares to control Neuphoria. The biotech’s social anxiety drug failed a Phase 3 trial last week, and the company decided to drop the asset, named BNC210. The biotech’s stock price $NEUP was up almost 6% in premarket trading on Tuesday. — Kyle LaHucik 💼 Aldeyra Therapeutics updates its pipeline: The biotech discontinued work on ADX-629 in patients with Sjögren-Larsson Syndrome. It also said it expects to file INDs for a pair of RASP modulators sometime next year. — Jaimy Lee 💰 X4 Pharmaceuticals ended up raising $155.3 million in its public offering, up from the $135 million it set out to raise. — Jaimy Lee