Pleasure across the sickle cell therapy market has been palpable. Across the starting of the yr, two new breakthrough gene modifying drugs — together with the primary FDA-approved CRISPR-based drug — gained approval for sickle cell indications, offering sufferers with probably healing care.
However a number of obstacles to entry have stored these therapies from reaching a large swath of sufferers and the therapy panorama is getting slimmer.
Final month, Pfizer introduced plans to yank its sickle cell drug Oxbryta from the market over security issues, leaving sufferers with one much less therapy and unanswered questions about learn how to safely cease the treatment.
Furthermore, affected person uptake for the 2 new gene therapies — Vertex Prescribed drugs and CRISPR Therapeutics’ Casgevy and bluebird bio’s Lyfgenia — has been sluggish.
Along with their multimillion-dollar worth tags, sufferers cleared for Casgevy face a frightening, months-long ex-vivo course of that features extracting stem cells from bone marrow, sending them to the producers for modification and chemotherapy to make room for the edited cells.
“They’ve been thought-about a practical treatment within the area. Nonetheless, they’re challenged by value, complexity and toxicity of supply,” mentioned Dr. Cameron Trenor, head of translational drugs for Cellarity, which is creating a sickle cell drug of its personal. “It appears onerous to get round that security barrier and the scalability challenges given the fee and complexity of producing.”
“The illness isn’t going away, and we’d like one thing that each one or virtually all sufferers can take.”
Dr. Cameron Trenor
Head, translational drugs, Cellarity
As of the top of September, simply 10 sufferers had began on Lyfgenia this yr, and bluebird just lately introduced plans to put off a few quarter of its workforce to chop prices.
On prime of that, a examine revealed this month revealed seven kids developed blood most cancers after receiving Skysona, bluebird’s gene remedy for a uncommon mind illness, recalling when bluebird quickly suspended trials for Lyfgenia (then referred to as LentiGlobin) after two sufferers developed most cancers in 2021.
The sickle cell pipeline has taken different hits too. Graphite Bio deserted its lead asset, a sickle cell gene modifying remedy, after a extreme antagonistic occasion occurred within the first dosed affected person. Now a newly shaped firm, Kamau Therapeutics, is attempting to revive that asset, whereas Graphite Bio isn’t any extra.
And regardless of the approval of one-and-done gene therapies, sufferers nonetheless face unmet wants, analysts say.
“[Sickle cell] stays a sexy development market with potential gross sales of $5 billion in 2030, regardless of Oxbryta’s withdrawal” due to the “clear unmet medical want,” in response to a consensus forecast offered to PharmaVoice from Consider, a Norstella firm.
“It is a profoundly devastating illness. It is basically a illness of hypoxia: not having the ability to get oxygen to your tissues nicely,” Trenor mentioned. “That manifests in silent and painful methods.”
Nonetheless ache is simply one of many results.
“Anyplace your blood goes is the place sickle cell illness impacts you,” Trenor mentioned. “It causes stroke, it causes coronary heart illness, it causes lung illness, it kills your spleen, it causes liver illness, it causes kidney illness.”
Consider factors to “a number of completely different gene modifying biotechs looking for to launch [sickle cell] therapies over the approaching years, along with a number of the largest pharma corporations.”
In line with a report from final yr, over 40 corporations are creating greater than 50 sickle cell remedies, together with Novo Nordisk, which has therapies in part 2 and three. Agios Prescribed drugs simply accomplished enrollment for a part 3 examine of its oral, small molecule PK activator, whereas GSK is in early growth with its DNMT1 inhibitor.
Moreover, sickle cell illness is “a proof-of-concept indication for brand new drug applied sciences,” the Consider forecast mentioned, pointing to the primary CRISPR medication for instance.
“The 2023 approvals for CRISPR/Vertex and bluebird bode nicely for the probabilities of a few of these next-generation cell therapies, and this competitors will assist to enhance affected person entry,” the forecast mentioned.
The Oxbryta withdrawal leaves the market with just some non-gene remedy medication together with hydroxyurea, which might cut back sickling of purple blood cells, and others aimed toward stemming ache. Hydroxyurea works by growing fetal hemoglobin, which reduces illness issues, but it surely additionally carries security dangers.
“It causes immunosuppression, so you possibly can’t push the dose larger, and that limits how a lot fetal hemoglobin, and subsequently how a lot profit you get,” Trenor mentioned.
Cellarity’s lead asset is an oral drug developed to induce fetal hemoglobin “to a stage that’s actually significant for sufferers,” Trenor mentioned.
“It’s identified from sufferers with mutations which have genetically excessive fetal hemoglobin, that if you may get over about 20% fetal hemoglobin you do not have many issues of sickle cell illness any longer,” he mentioned. “We’re hoping we’ll be capable of get sufferers as much as or above that stage with a small molecule, and that may be a paradigm shift within the area.”
Cellarity is within the IND-enabling part and plans to start out medical trials subsequent yr. The corporate hopes the oral therapy will assist bridge the entry divide.
“The illness isn’t going away, and we’d like one thing that each one or virtually all sufferers can take,” Trenor mentioned.
