Konkurrenten Travere har fått utsatt PDUFA:
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Good news, ikke uventet. 
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Pareto: Osannolikt att Traveres kandidat sparsentan godkänns
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Updated: 2022-10-14 11:21
Det är osannolikt att Calliditaskonkurrenten Traveres får grönt ljus för sin kandidat sparsentan. Det skriver Pareto i en kommentar avseende att FDA uttryckt oro kring levertoxicitet för kandidaten.
“Som ett resultat kommer (i) sparsentan (om den godkänns) att få en blackbox-varning för levertoxicitet (bekräftat av Travere i telefonkonferensen men utelämnat i pressmeddelandet), (ii) sparsentan-behandlade patienter måste övervakas för levertoxicitet som en del av en riskutvärderingsstrategi (REMS) och (iii) fördröjs potentiellt accelererat godkännande till åtminstone mitten av januari 2023”, skriver analyshuset.
Även om spersentan blir godkänt nästa år tror banken att dessa säkerhetsproblem (blackbox-varning och leverövervakningskrav) väsentligt kommer att påverka den potentiella adoptionen.
Mäklarhuset upprepar sin köprekommendation för Calliditas med riktkurs 300 kronor.
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Det er jo ikke bra for shortepakket som må handle ca. 1,9mill aksjer når den første konkurrenten i beste fall bare får 3 mnd utsettelse. Det betyr 3mnd ekstra i den viktigste fasen for CALTX hvor de kan herje alene! Let’em burn!
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Med alt som har skjedd og fortsatt skjer i verden, nå spesielt med utfordringene vi har i Europa har jeg begynt å tenke litt mer i baner å også sikre meg mot valuta.
Per nå er jeg relativt tungt investert i CALTX, på bakgrunn av hva de har levert og hva jeg forventer de skal levere de neste årene. Men når en ser på valutaendringene det siste året virker det å kunne være en fin hedge ift USD også, som enda ikke har materialisert seg i aksjekursen hos CALTX. Inntektene er jo i dollar, samtidig som de største utgiftene er i SEK (som jeg har forstått, dette er utenom organisasjonen i USA).
Her er et par chart over utviklingen det siste året:
USD / SEK (datoen merket er random):
SEK / NOK:
Kun på valutagevinsten USD / SEK bør det vel være en fin hedge?
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Det kom en oppdatering fra RedEye angående Travere:
REDEYE RESEARCH NOTE
Calliditas: Comfortably ahead
2022-10-17
09:58
We have taken a sceptical view regarding the potential threat from Sparsentan (Travere Therapeutics) ahead of additional long-term data from more extensive studies regardless of an early (premature) approval or not. Hence we are not highlighting the impact of the recent delayed Sparsentan PDUFA date.
Johan Unnerus
FDA has asked for a REMS (Risk Evaluation and Mitigation Strategy) for Sparsentan (to include liver monitoring) related to the risk of liver implication which can be considered a potential class risk for Sparsentan (endothelin receptor antagonist). As a result, the PDUFA date is delayed by at least three months (initially set for 17th November). Does this have any relevance for Tarpeyo/Calliditas. We would argue that even if and when Sparsentan is approved for IgAN, it needs to show robust competitive evidence from future, more extensive pending studies. As a result, we regard this REMS requirement as of limited relevance for Tarpeyo. We also note:
- It’s better to have an approved product without a REMS requirement.
- A REMS requirement might be negative once approved when an established product is available without a REMS.
- From a clinical perspective, it is probably even more critical that Sparsentan can show a significant future advantage ahead of Tarpeyo to compensate for this risk.
- A REMS requirement may reduce the likelihood of an early approval at the delayed PDUFA date, which is not favourable in any event. IgAN is associated with liver scarring (fibrosis).
This may also reduce the Sparsentan’s relevance for IgAN patients with liver scarring or established chronic liver disease that tends to be associated with IgAN.
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Gode nyheter, men det bryr ikke børsen seg om!
Calliditas Therapeutics: Kidney International Publishes Results from NefIgArd Phase 3 Trial Evaluating TARPEYO[®] (budesonide) in IgA Nephropathy
19.10.2022 15:30 • Cision •
Kopier link
Calliditas Therapeutics AB (Nasdaq: CALT, Nasdaq Stockholm: CALTX) (“Calliditas”) today announced Kidney International has published the successful results from NefIgArd Part A, their pivotal Phase 3, randomized, double-blind, placebo-controlled, multicenter study.
The publication highlights the safety results and efficacy data related to both proteinuria and estimated glomerular filtration rate (eGFR) for patients treated with TARPEYO while on background of optimized and stable renin-angiotensin system inhibitor (RASi) therapy.
“The publication of data from our NefIgArd Phase 3 study will address physician requests related to more comprehensive information regarding the mode of action and efficacy of TARPEYO, the first and only FDA-approved treatment specifically designed for this disease,” said Renée Aguiar-Lucander, Chief Executive Officer of Calliditas. "We are excited to share these data and see this as reinforcing evidence of the differentiation we believe that TARPEYO represents, as well as its potential to be disease modifying. "
IgAN is a chronic autoimmune disease with a significant burden of disease, with more than 50% of patients progressing to end-stage kidney disease within 20 years of initial diagnosis.[2 ]
The peer-reviewed article can be viewed here. (https://www.kidney-international.org/article/S0085-2538(22)00836-5/fulltext)
INDICATION and IMPORTANT SAFETY INFORMATION
Indication
TARPEYO® (budesonide) delayed release capsules is a corticosteroid indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.
This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
Important Safety Information
Contraindications: TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations.
Warnings and Precautions
Hypercorticism and adrenal axis suppression: When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy [see Dosing and Administration] or switching between corticosteroids, monitor for signs of adrenal axis suppression.
Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B).
Risks of Immunosuppression: Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressive doses of corticosteroids. Avoid corticosteroid therapy in patients with active or quiescent tuberculosis infection; untreated fungal, bacterial, systemic viral, or parasitic infections; or ocular herpes simplex. Avoid exposure to active, easily transmitted infections (eg, chicken pox, measles). Corticosteroid therapy may decrease the immune response to some vaccines.
Other corticosteroid effects: TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataracts, a family history of diabetes or glaucoma, or with any other condition in which corticosteroids may have unwanted effects.
Adverse reactions: In clinical studies, the most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO patients and ≥2% higher than placebo) were hypertension (16%), peripheral edema (14%), muscle spasms (13%), acne (11%), dermatitis (7%), weightincrease (7%), dyspnea (6%), face edema (6%), dyspepsia (5%), fatigue (5%), and hirsutism (5%).
Drug interactions: Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide.
Use in specific populations
Pregnancy: The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN. Infants exposed to in utero corticosteroids, including budesonide, are at risk for hypoadrenalism.
Please see Full Prescribing Information for TARPEYO here (https://bit.ly/3z5jnMR).
About the NefIgArd Study
The global clinical trial NefIgArd is an ongoing Phase 3, randomized, double-blind, placebo- controlled, multicenter study to evaluate the efficacy and safety of TARPEYO 16 mg once daily vs placebo in adult patients with primary IgAN (N=360) as an addition to optimized RASi therapy.
Part A of the study included a 9-month blinded treatment period and a 3-month follow-up period. The primary endpoint was UPCR, and eGFR was a secondary endpoint. Part B is a confirmatory validation study for full approval that will assess eGFR over 2 years for patients who were treated with the TARPEYO or placebo regimen in Part A.
The trial met its primary objective in Part A of demonstrating a statistically significant reduction in urine protein creatinine ratio, UPCR or proteinuria, after 9 months of treatment with 16 mg once daily of TARPEYO compared to placebo. Patients taking TARPEYO plus RASi (n=97) showed a statistically significant 34% reduction from baseline vs 5% with RASi alone (n=102) at 9 months, resulting in UPCR reduction of 31% (16% to 42%) p=0.0001.[3]
At 12 months, a 53% reduction in UPCR from baseline was seen in the TARPEYO plus RASi-treated group (n=97) vs 9% with RASi alone (n=102). Additional data presented prior to or beyond the primary endpoint of 9 months or from subgroup analyses should be interpreted cautiously.[3]
At 9 months, there was a 3.87 mL/min/1.73 m2 difference in eGFR absolute change with TARPEYO plus RASi vs RASi alone (-0.17 vs. -4.04).[4]
In a separate analysis at 9 months (based on the analysis of the full patient population including patients who received rescue treatment), absolute change in eGFR was -0.6 mL/min/1.73 m2 with TARPEYO plus RASi (n=97) vs -4.0 mL/min/1.73 m2 with RASi alone (n=102).[3] These interim data were not prospectively controlled for multiplicity and need cautious interpretation. The clinical significance of these results is unknown. Confirmatory clinical trial results are required to draw any conclusions. It has not been established whether TARPEYO has demonstrated a benefit in slowing kidney function decline in patients with IgAN.
About Primary Immunoglobulin A Nephropathy
Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger’s Disease) is a rare, progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose-deficient IgA1 are recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney.[5,6] This deposition in the kidney can lead to progressive kidney damage and potentially a clinical course resulting in end-stage renal disease. IgAN most often develops between late teens and late 30s.[6,7]
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Hva skjedde her? Tolket vi nyheten helt feil?
Dette er data som, etter hva jeg har forstått, allerede var en del av pakken til FDA, så jeg tror ikke det.
Jeg fikk meg nå noen tusen til i dag.
Var det black box som førte til stupet?
Det er da ingenting som tilsier at de skal få black box warning, all den tid dette er kjente data for FDA?
Det gjorde jeg også😊
Skjønner ikke hvordan den kan stupe 17% på godt nytt🧐
Var det noe negativt med denne teksten?
At 9 months, there was a 3.87 mL/min/1.73 m2 difference in eGFR absolute change with TARPEYO plus RASi vs RASi alone (-0.17 vs. -4.04).4
In a separate analysis at 9 months (based on the analysis of the full patient population including patients who received rescue treatment), absolute change in eGFR was -0.6 mL/min/1.73 m2 with TARPEYO plus RASi (n=97) vs -4.0 mL/min/1.73 m2 with RASi alone (n=102).3
This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
Forstår jeg det rett her at det må en ny clinical trial til for og vurdere kost /nytte av Tarpeyo eller har jeg misforstått? og i tilfelle må vel det tolkes negativt?
Spør for morra mi! 
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Kanskje FiloD kan svare mora di 
?
De skal lese av en studie ila H1-23 før de sender inn søknad om full approval.
Igjen, dette er kjente data for FDA som de har gitt AA på.
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Greit nok men et fall på 17% ut av det blå er jo ikke hverdags akkurat. De ga vel uttrykk for at de ikke trengte mer penger heller hvis jeg ikke husker feil , så en ny emisjon er vel utelukket også.
Takk for svar!
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Det er en misforståelse.
Dette er data som er kendt for FDA, og er de data som er grundlaget for en midlertidig godkendelse. Når de siger at de skal bruge yderligere studier, så er det en pågående studie som @solskimm og René siger:
"We are excited to share these data and see this as reinforcing evidence of the differentiation we believe that TARPEYO represents, as well as its potential to be disease modifying. ”
Denne studie og disse data bliver færdig i H1, 2023. Det har i princippet intet med den midlertidige godkendelse at gøre.
Dersom disse data ikke er gode nok, når de kommer i 2023, kan FDA fratage CALTX, den midlertidige AA godkendelse. Det er dog meget sjældent at det sker.
Vedr. Kursen så er det mange som fisker i panikken og uvidenheden.
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Ned 17% uten nyheter skal ikke være mulig i et effisient marked.
Det må være en spesifikk grunn for dette fallet
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