By Alex Philippidis
Novo Nordisk (NVO) continued its year-long stock surge this week when it halted a Phase III trial early due to undisclosed efficacy results suggesting that its blockbuster adult type 2 diabetes drug Ozempic® (semaglutide)—which shares the same active ingredient as its obesity drug Wegovy® (semaglutide injection)—is also an effective treatment for chronic kidney disease (CKD).
Novo Nordisk announced an early halt to its Phase III FLOW trial (NCT03819153), designed to compare semaglutide with placebo in the progression of renal impairment in people with type 2 diabetes and chronic kidney disease. The company cited a recommendation from the study’s independent Data Monitoring Committee (DMC) following results from an interim analysis that were not shared in a press release announcing Novo Nordisk will begin closing the trial.
Results from FLOW are expected to be read out during the first half year of 2024, Novo Nordisk said.
Launched in 2019, FLOW enrolled 3,534 patients and has been conducted at more than 400 investigator sites in 28 countries. According to baseline data published August 31 in Nephrology Dialysis Transplantation, enrolled participants had a baseline mean age of 66.6 years, haemoglobin A1c of 7.8%, diabetes duration of 17.4 years, an estimated glomerular filtration rate (eGFR) of 47.0 ml/min/1.73 m2 (SD 15.2) and median urine albumin-creatinine ratio (uACR) of 568 mg/g (range 2‒11 852), with 68.2% of patients at “very high risk” for CKD progression.
The CKD market is projected to grow from $32 billion as of last year to $47.9 billion by 2032, at a compound annual growth rate of 4% from 2023 to 2032, Allied Market Research has projected.
Acing the Phase III trial helped Novo Nordisk maintain a rising stock price, with shares on Nasdaq Copenhagen climbing 5% on Wednesday, from DKK 650.10 ($92.49) to DKK 681.80 (an even $97), then another 4% on Thursday, to DKK 710.20 ($100.47). Novo’s American depositary receipts (ADRs) on Nasdaq in New York rose 6% Wednesday from $93.01 to $98.84, and another 1.5% on Thursday as of 12:49 p.m. ET, to $100.29.
Novo Nordisk has seen its shares rise 13% since October 3, when they closed at DKK 625.70 ($89.04), a day after the company won FDA approval for another drug with a kidney-related indication—RivflozaTM (nedosiran) injection, a once-monthly subcutaneous RNA interference (RNAi) therapy designed to lower urinary oxalate levels in children ages nine and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function.
Novo’s ADRs have risen 14% from $87.78 on October 3.
Near doubling year-over-year
More impressively, however, Novo Nordisk shares have surged 45% since January, when they began the year trading at DKK 471 ($67.04)—and have soared 71% over the past 12 months, from DKK 398.60 ($56.73) on October 11, 2022. That surge has transformed Novo Nordisk market capitalization—the product of the share price and the number of outstanding shares—into the second highest in Europe behind Nestle, according to Morningstar. Based on that market cap, Novo Nordisk topped GEN’s A-List of Top 25 Biotech Companies of 2023, published in May.
U.S. investors have been even more bullish on Novo Nordisk as its ADRs year-over-year have nearly doubled, rocketing 88.5% from $52.19 on October 11, 2022.
The ADR and stock surges reflect growing patient demand for drugs indicated for diabetes—and especially weight loss, since semaglutide is also the active ingredient in Novo Nordisk’s obesity drug Wegovy.
Investors apparently agree with Novo Nordisk’s apparent conclusion that Ozempic, as with other GLP-1 receptor agonists, have “therapeutic benefits far beyond their original intended purpose, according to Emily Field, director, head of European Pharmaceuticals Equity Research with Barclays, as reported by Reuters.
During the first half of this year, sales of Ozempic jumped 58%, from DKK 26.384 billion (about $3.758 billion) to DKK 41.741 billion ($5.945 billion), after zooming 77% last year, to DKK 59.750 billion ($8.509 billion) from DKK 33.705 billion ($4.8 billion) in 2021.
Also benefiting from Novo Nordisk’s good Ozempic news is Eli Lilly, whose stock has increased 6% earlier this week, from $571.76 on Monday to $605.28 on Wednesday. Lilly markets the type 2 diabetes drug Mounjaro® (tirzepatide), to which the company is working to add an approval as a treatment of adults with obesity, or overweight with weight-related comorbidities. Lilly has a rolling submission to the agency for approval of the obesity indication, and has reported positive results earlier this year from three Phase III trials: SURMOUNT-2 (NCT04657003), SURMOUNT-3 (NCT04657016) and SURMOUNT-4 (NCT04660643).
Mounjaro has already reached blockbuster status, with January–June 2023 sales of $1.548 billion, multiples of the $16 million racked up in the first half of last year (all of it in June 2022, the month Mounjaro was commercially launched). For all of last year, Mounjaro generated $482.5 million in sales according to Lilly.
Morningstar has projected that sales of Ozempic will rise to earn $19.3 billion in 2027 and about $20 billion in 2030. Lilly’s Mounjaro® (tirzepatide) future sales have been pegged even higher at $21.2 billion in 2027, while Wegovy, a next-gen once-weekly injection version of semaglutide approved in 2021, is projected to earn $12.5 billion in 2027.
Dodging a Bullet
Novo Nordisk dodged a proverbial bullet October 2 when the U.S. Patent and Trademark Office (USPTO)’s Patent Trial and Appeal Board (PTAB) denied an inter partes review (IPR) request by Mylan Pharmaceuticals, a generic drug company owned by Viatris, challenging Novo’s two key composition of matter patents for semaglutide, Nos. 8,129,343 and 8,536,122.
IPRs are designed to review the patentability of one or more claims in a patent based on two of the three patentability criteria, novelty and non-obviousness. In challenging the patents of Novo Nordisk, Viatris hopes to accelerate the arrival to market of the first generic version of Ozempic.
“VTRS’s arguments against the patents appeared weak, & we expected NVO to win,” Jefferies equity analyst Akash Tewari and colleagues wrote October 2 in a research note.
Two days later, however, the PTAB granted a separate IPR request to review the patentability of 10 claims within a third semaglutide patent, No. 10,335,462, covering dosing regimens: “We are persuaded that Petitioner has demonstrated a reasonable likelihood that it would prevail with respect to at least one claim challenged in the Petition,” according to the decision, written by Administrative Patent Judge Susan L.C. Mitchell.
While Novo Nordisk has vowed to vigorously defend the ‘462 patent, Tewari said the setback for the company isn’t as significant as it could have been.
“We don’t think this is a key patent as it only covers Ozempic, & the key claim is treating T2DM pts [type 2 diabetes patients] with a dose of 1.0 mg weekly,” Tewari and colleagues noted, citing the dosage of up to 2.4 mg weekly used in another clinical study—the Phase III SELECT trial (NCT03574597), a placebo-controlled, 17,609-participant study designed to assess whether semaglutide can reduce the risk of cardiovascular events in patients who are overweight or obese, with prior cardiovascular disease.
Two other challenges remain for Ozempic. Novo Nordisk is seeking to stop compounded versions of Ozempic as well as Wegovy from reaching the market. The company has sued four compounding pharmacies led by Brooksville Pharmaceuticals in U.S. District Court for the Middle District of Florida, Tampa Division, arguing that the compounded versions were never approved by the FDA. U.S. District Judge William F. Jung dismissed the suits on October 5, but Novo Nordisk has said publicly it plans to refile them.
Another challenge looming is Medicare drug-price negotiation, with Cantor Fitzgerald analyst Louise Chen telling CNBC in August that the drug may be among those chosen by the federal agency for discussions: “Ozempic is going to be the biggest one that people are going to watch really closely in the second round of negotiations.”
Leaders & Laggards
- Akero Therapeutics (AKRO) shares have plunged 70% over two days after the company disappointed investors with results from its Phase IIb SYMMETRY trial (NCT05039450) assessing lead product candidate efruxifermin (EFX) in patients with compensated cirrhosis (F4) due to NASH. EFX missed the study’s primary endpoint of achieving a one-stage or better improvement in liver fibrosis without worsening NASH, following 36 weeks of treatment with EFX vs. placebo. However, Akero cited a positive trend of 22% and 24% of the 28mg and 50mg EFX-treated groups, respectively, experiencing at least a one-stage improvement, vs. 14% for placebo. “We believe EFX has the potential to show additional improvements for patients after the long-term follow-up period is complete at Week 96,” Akero president and CEO Andrew Cheng, MD, PhD, stated. Shares plummeted 63% from $48.54 to $18.15 on Tuesday, and fell another 19% on Wednesday, to $14.68.
- Tempest Therapeutics (TPST) shares soared into the stratosphere, zooming more than 4,000% from 24 cents to $9.77 on Wednesday, after the company released updated positive results from an ongoing global Phase Ib/II clinical trial (NCT04524871) in which the lead program of the peroxisome proliferator-activated receptor alpha (PPAR⍺) antagonist TPST-1120 showed clinical superiority in multiple endpoints when combined with Tecentriq® (atezolizumab) and Avastin® (bevacizumab) in a randomized comparison to the two Roche (Genentech) marketed cancer drugs in the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC). Data showed a confirmed objective response rate of 30% for the TPST-1120 triplet arm versus 13.3% for atezolizumab and bevacizumab. Duration of response has not yet been reached.
- Teva Pharmaceutical Industries (TEVA) American depositary shares rose 2.5% over two days while its shares traded on the Tel Aviv Stock Exchange inched up about 1%, from ILS 3,608 ($909.03) to ILS 3,631 ($914.87) Wednesday, after the Israeli-headquartered drug developer said Tuesday it did not foresee a “meaningful” impact from Israel’s war against Hamas. Teva said its revenues in Israel last year accounted for approximately 2% of its $14.9 billion in global revenues, while production in Israel constituted less than 8% of its total global production in U.S. dollars. Production remains “largely unaffected,” the company added. “As an Israeli company we condemn this appalling assault and Teva stands with Israel in this time of great loss and challenge,” Teva declared.
- Ventyx Biosciences (VTYX) shares nosedived 37% over 2–1/2 trading days despite reporting positive results from a Phase II trial (NCT05156125) assessing the oral S1P1 receptor modulator VTX002 in moderate-to-severely active ulcerative colitis (UC). Ventyx reported that 28% of patients on the 60 mg dose and 24% of patients on the 30 mg dose achieved the trial’s primary endpoint of clinical remission at Week 13 compared to 11% of placebo But investors appeared unimpressed since Ventyx is trying to compete with Bristol-Myers Squibb, whose UC drug Zeposia® (ozanimod) won FDA approval in 2020, and Pfizer, whose UC candidate etrasimod is under FDA and European Medicines Agency review. Shares skidded 26% Tuesday, from an even $30 to $22.22, slipped 9% on Wednesday, to $20.25, and fell another 7% to $18.84 Thursday as of 12:30 p.m.
Alex Philippidis is Senior Business Editor of GEN.