“Third time’s the appeal,” the previous saying goes, however for Abeona Therapeutics (NASDAQ: ABEO), the second time round proved profitable for the corporate’s first-ever pipeline candidate to make it by means of medical trials.
The FDA authorized Abeona’s Zevaskyn™ (prademagene zamikeracel) as the primary (and to date solely) cell-based gene remedy to be licensed for recessive dystrophic epidermolysis bullosa (RDEB), a uncommon connective tissue pores and skin dysfunction brought on by mutations within the COL7A1 gene.
RDEB sufferers lack purposeful Kind VII collagen, leading to extraordinarily fragile pores and skin that blisters simply, resulting in painful persistent wounds that always cowl greater than 30%, and generally as much as 80%, of a affected person’s physique floor, in addition to elevated an infection danger and elevated danger of squamous cell most cancers. Till lately, remedy choices have been restricted to wound care and ache administration relatively than addressing the underlying genetic trigger.
Zevaskyn consists of a affected person’s personal keratinocytes, pores and skin cells which are genetically modified to supply purposeful Kind VII collagen. Zevaskyn gene-modified mobile sheets are utilized by way of surgical procedure to a affected person’s wounded areas, with a producing run capable of provide as much as 12 credit score card-sized sheets that may be joined collectively in a single utility of the remedy to cowl a big space or utilized to a number of wounds.
“Software of tiles”
“It’s nearly like an utility of tiles to cowl a big space. And in case you have a smaller space, one or two, or three sheets can cowl that. So there’s flexibility of what number of sheets you employ, and it may be finished in a single sitting,” Abeona president and CEO Vishwas (Vish) Seshadri, PhD, informed GEN Edge.
Zevaskyn received FDA approval upon Abeona’s second submitting of a biologics license utility (BLA) for the remedy. The primary BLA was rejected final yr, by means of an FDA Full Response Letter citing chemistry, manufacturing, and controls (CMC) issues associated to Zevaskyn, however not questioning its security and efficacy as proven in medical information.
“They [the FDA] in all probability didn’t anticipate that stage of complexity in our product, and weren’t ready for it. That’s what triggered them to present us an entire response letter and provides us these objects to handle,” Seshadri mentioned. “And we did precisely that, which is why we obtained the approval.”
The FDA based mostly its approval on constructive information from the Section III VIITAL trial (NCT04227106) displaying that throughout 43 giant and persistent wounds handled with a single utility of Zevaskyn, 81% of the injuries had healed by ≥50% after six months, in comparison with 16% of wounds receiving customary care. Fewer than 5% of sufferers skilled unwanted side effects equivalent to procedural ache or itch.
In approving Zevaskyn, the FDA additionally granted Abeona a Uncommon Pediatric Illness Precedence Overview Voucher (PRV), which the corporate plans to promote.
Traders responded to the FDA’s approval of Zevaskyn with a shopping for surge that despatched Abeona’s inventory worth hovering 30% over two days, from $5.30 to $6.56 Wednesday, when it scored its 52-week excessive of $7.08—then as much as $6.87 Thursday, earlier than sliding 4.5% Friday to $6.56.
“We noticed danger in approval, getting a PRV, pricing, and pot’l for label surprises, and the replace appeared (+)ve [positive] to us throughout the board,” Maury Raycroft, PhD, fairness analyst with Jefferies, and 4 colleagues wrote April 29 in a analysis word. Raycroft raised his agency’s 12-month worth goal on Abeona shares 21%, from $14 to $17.
$108M income projected for 2026
Raycroft projected Zevaskyn will obtain $108 million in income subsequent yr, its first full yr available on the market. “I believe that’s fairly good,” Seshadri mentioned of the estimate, which relies on remedy of 45 sufferers.
The corporate informed buyers in March that it estimated peak-year annual U.S. income for the remedy of greater than $500 million.
That’s greater than double the $290.5 million generated final yr by Krystal Biotech’s marketed remedy Vyjuvek® (beremagene geperpavec-svdt)—the third highest gross sales of any gene remedy in 2024, in keeping with an up to date A-Record to be printed by GEN.
In contrast to Zevaskyn, Vyjuvek is a gel utilized weekly. Vyjuvek is a Herpes-simplex virus sort 1 (HSV-1) vector-based gene remedy that received FDA approval in 2023 to deal with wounds in sufferers six months of age and older with dystrophic epidermolysis bullosa (DEB) with mutation(s) within the collagen sort VII alpha 1 chain (COL7A1) gene. RDEB is a extreme type of DEB.
Amongst medical candidates for RDEB is allo-APZ2-CVU, a first-in-class intravenous stem cell remedy that makes use of ABCB5-positive mesenchymal stem cells (MSCs) to deal with sufferers with extreme immune and inflammation-driven illnesses with excessive unmet medical want. Developed by Rheacell, allo-APZ2-CVU is underneath research in a Section III trial (NCT05838092).
Final yr, Phoenicis Therapeutics studied PTW-002, an antisense oligonucleotide (AON)-mediated RNA regulation remedy in a Section I/II trial (NCT05529134) in sufferers with RDEB or dominant DEB as a result of mutation(s) in exon 73 of the COL7A1 gene. The corporate’s web site has since been taken on-line, and no outcomes have been posted for the trial.
First Zevaskyn affected person set for Q3
Abeona plans to slowly however steadily improve the provision of Zevaskyn beginning within the third quarter, when it expects to deal with the primary affected person. Ten to 12 sufferers are anticipated to be handled this yr. If 12 sufferers are handled, Abeona stands to make $28.4 million in income, Raycroft estimated.
The corporate will make Zevaskyn accessible by means of 5 Certified Remedy Facilities (QTCs) anticipated to be established by the third quarter. The websites will likely be disclosed as soon as activated.
Manufacturing will likely be ramped as much as six Zevaskyn remedies per 30 days by the tip of 2025, then as much as 10 per 30 days within the first half of 2026. Abeona will commercially manufacture Zevaskyn at its totally built-in cell and gene remedy cGMP manufacturing facility in Cleveland, the place the corporate is headquartered.
“We’re beginning with a capability to provide about 4 models a month. Once we launch, which is in July, we’ve mentioned that we anticipate treating the primary affected person and ramping up that capability. Within the first half of 2026, we must always hit that 10-per-month cadence,” Seshadri mentioned. “Revenues will likely be pushed not simply by the demand, what number of sufferers there are on the market in search of remedy. It’s really extra of how a lot we are able to provide.”
$3.1M price ticket
Zevaskyn carries a listing worth or “wholesale acquisition price” of $3.1 million per one-time remedy, making it one of many priciest gene therapies ever authorized. The costliest is Lenmeldy™ (atidarsagene autotemcel), a remedy for early-onset metachromatic leukodystrophy, which is list-priced at $4.25 million and marketed by Kyowa Kirin-owned Orchard Therapeutics.
Seshadri defended the checklist worth by saying it wanted to be seen in context of:
- Present price of care, which may run about $1 million a yr for RDEB sufferers, a lot of whom die of their 30s or 40s
- The price of different gene therapies
- The shortage of different remedy choices
“There is no such thing as a remedy. They reside in fixed ache all their lives. And we’re attempting to make a giant distinction to their high quality of life,” Seshadri mentioned.
Abeona mentioned it plans to broaden entry to Zevaskyn by means of its Abeona Help™ program, which is designed to supply personalised assist, together with serving to sufferers perceive their insurance coverage advantages and monetary help choices, and offering journey and logistical help for eligible sufferers.
Healthcare suppliers will provide Zevaskyn by means of value-based agreements with payers that tie reimbursement to affected person care outcomes relatively than quantity of sufferers handled. Seshadri mentioned authorities payers will be capable of hammer out value-based reimbursement agreements now that Zevasky has attained FDA approval, whereas the corporate has had talks with a number of personal insurers: “No one has blinked at our pricing. They see the worth, so there’s going to be protection for these sufferers.”
“We’re going to make it possible for whether or not you’re a affected person that’s coated by personal industrial insurance coverage or Medicaid, and even the small subset of sufferers which will have Medicare for incapacity, we’re going to make it possible for their entry goes to be accessible,” Seshadri mentioned. “We’re standing behind our product.”
Which means if a affected person comes for repeat remedy of a wound, payers obtain rebates from the corporate.
As a result of Zevaskyn had beforehand been designated a uncommon pediatric illness drug, it was grandfathered underneath the company’s Uncommon Pediatric Illness PRV program, regardless of it beginning to sundown on December 20, 2024, after Congress didn’t agree on a renewal.
Skyrocketing voucher values
Because of the sundown, the typical worth of PRVs has skyrocketed from the $100 million cited in a research printed final yr to $150 million.
“We consider that we must always be capable of obtain that form of sale, however it’s at all times going to be a tradeoff with how shortly we need to do it, as a result of even people who bought for 150, generally they began considerably decrease, or the businesses held off promoting for months,” Seshadri noticed.
The 2024 research discovered particular person vouchers had bought for between $67.5 million and $350 million.
“Now we have to monetize the PRV relatively shortly. However what we’re assured about is that second quarter-ish of 2026, we needs to be a worthwhile entity,” Seshadri mentioned. “If we monetize the PRV shortly, it’s going to bridge us to profitability.”
Seshadri mentioned Abeona can use the cash it could generate from a PRV sale, since its money runway is just sufficient to take the corporate into 2026. Abeona completed 2024 with accessible money, money equivalents, short-term investments, and restricted money of $98.1 million, up 87% from $52.6 million as of December 31, 2023.
Abeona completed 2024 with a web lack of $63.7 million, 17.5% above the corporate’s $54.2 million web loss for 2023. Abeona recorded no income final yr and solely $3.5 million in 2023.
Abeona has a workforce of “150-plus” that’s anticipated to increase as the corporate grows its manufacturing, notably high quality assurance/high quality management (QA/QC) employees.
“Principally manufacturing personnel and technical operations are going to extend. Principally, the whole lot that should assist the scale-up of Zevaskyn provide,” Seshadri mentioned.
The sooner it may scale up Zevaskyn provide, the higher in a position Abeona will likely be to maximise two alternatives—treating RBED sufferers with the primary one-time remedy accessible for the dysfunction, and advancing uncommon illness genetic medicines, in keeping with Paula Cannon, PhD, president of the American Society of Gene + Cell Remedy (ASGCT) for 2024–2025.
“This landmark approval represents a big breakthrough for sufferers affected by this devastating pores and skin dysfunction,” mentioned Cannon, who can be a distinguished professor of molecular microbiology & immunology on the College of Southern California (USC)’s Keck Faculty of Medication. “This approval not solely brings hope to these residing with RDEB but additionally represents important progress basically for gene-corrected cell therapies for uncommon genetic problems.”
Leaders and laggards
- Ardelyx (NASDAQ: ARDX) shares skidded 24.5% from $5.47 to $4.13 on Friday, after the corporate’s inventory was downgraded from “Sturdy Purchase” to “Outperform” by Raymond James, which sliced its worth goal on the corporate’s shares 15%, from $13 to $11. Raymond James reacted to Ardelyx asserting first-quarter outcomes that missed analyst expectations. Ardelyx completed Q1 with a $41.1 million web loss or $(0.17) per share vs. a web lack of $26.5 million or $(0.11) per share in Q1 2024, reflecting elevated prices related to ongoing commercialization of tenapanor, marketed as Ibsrela® for grownup irritable bowel syndrome with constipation and as Xphozah® for persistent kidney illness in adults on dialysis. Revenues jumped 61% from $46 million to $74.1 million, which the corporate mentioned mirrored elevated web product gross sales and licensing income.
- Immunic (NASDAQ: IMUX) shares yo-yoed this week, tumbling 23% from $1.28 to 99 cents Tuesday, then rising 18% to $1.17 Wednesday after the corporate reported topline information that buyers initially thought-about disappointing from its Section II CALLIPER trial (NCT05054140) assessing its a number of sclerosis (MS) drug vidofludimus calcium (IMU-838). Immunic mentioned vidofludimus calcium remedy resulted in a 5% enchancment in annualized charge of p.c mind quantity change vs. placebo after two years of remedy, a “modest profit” on the exploratory main MRI endpoint. The drug was additionally proven to cut back the annualized charge of thalamic mind quantity loss by 20% in sufferers with progressive MS vs. placebo, and cut back by 30% the relative danger of 24-week confirmed incapacity worsening occasions within the 152-patient main progressive a number of sclerosis (PPMS) research inhabitants vs. placebo.
- Organon (NYSE: OGN) shares nosedived 27% from $12.93 to $9.45 after the corporate all however worn out its quarterly dividend 93%, from 28 cents per share to 2 cents per share. The transfer is predicted to redirect $200 million into debt discount. “Now we have reset our capital allocation priorities to speed up progress in the direction of deleveraging, enabling a path to realize a web leverage ratio of under 4.0x by year-end,” Organon CEO Kevin Ali said. “Beneath 4.0x” means lower than 4 occasions earnings earlier than curiosity, taxes, depreciation, and amortization (EBITDA). “By deleveraging extra quickly, we are going to proceed to strengthen the longer term prospects of the corporate,” Ali added.” The dividend is payable June 12 to stockholders of report on the shut of enterprise on Might 12. Organon focuses on ladies’s well being, biosimilars, and established medicines throughout a spread of therapeutic areas.
- Regulus Therapeutics (NASDAQ: RGLS) shares greater than doubled, rocketing 137% from $3.37 to $7.98 Wednesday after Novartis (SIX Swiss: NOVN:SW) introduced it dedicated as much as $1.7 billion to amass the microRNA therapeutics developer targeted on autosomal dominant polycystic kidney illness (ADPKD), the most typical genetic explanation for renal failure worldwide. The deal would bolster the client’s cardiovascular, renal, and metabolic therapeutic space with Regulus’ lead asset arabursen, a next-generation, miR-17-targeting oligonucleotide that lately accomplished a Section Ib multiple-ascending dose medical trial. Novartis agreed to pay Regulus $800 million upfront, and as much as $900 million tied to attaining an undisclosed regulatory milestone. Novartis shares on the SIX Swiss Trade dipped 0.45% from CHF 94.21 ($113.95) to CHF 93.79 ($113.44).
